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Abstract Prenatal stress exerts long-term impact on neurodevelopment in the offspring, with consequences such as increasing the offspring’s risk of depression in adolescence and early adulthood. S-ketamine can produce rapid and robust antidepressant effects, but it is not clear yet whether and how S-ketamine alleviates depression in prenatally stressed offspring. The current study incestigated the preliminary anti-depression mechanism of S-ketamine in prenatally stressed offspring, particularly with regard to neuroplasticity. The pregnant females were given chronic unpredictable mild stress on the 7th-20th day of pregnancy and their male offspring were intraperitoneally injected with a single dose of S-ketamine (10 mg/kg) on postnatal day 42. Our findings showed that S-ketamine treatment counteracted the development of depression-like behaviors in prenatally stressed offspring. At the cellular level, S-ketamine markedly enhanced neuroplasticity in the CA1 hippocampus: Golgi-Cox staining showed that S-ketamine alleviated the reduction of neuronal complexity and dendritic spine density; Transmission electron microscopy indicated that S-ketamine reversed synaptic morphology alterations. At the molecular level, by western blot and RT-PCR we detected that S-ketamine significantly upregulated the expression of BDNF and PSD95 and activated AKT and mTOR in the hippocampus. In conclusion, prenatal stress induced by chronic unpredictable mild stress leads to depressive-like behaviors and hippocampal neuroplasticity impairments in male offspring. S-ketamine can produce antidepressant effects by enhancing hippocampal neuroplasticity via the BDNF/AKT/mTOR signaling pathway.

Abstract Background Adverse pregnancy outcomes have reached epidemic proportions in recent years with serious health ramifications, especially for diverse cancers risk. Therefore, we carried out an umbrella review to systematically evaluate the validity and strength of the data and the extent of potential biases of the established association between adverse pregnancy outcomes and cancers risk in both mother and offspring. Methods PubMed, Embase, and Web of Science databases were searched from inception until 18 January 2024. Meta-analyses of observational studies investigating the relationship between adverse pregnancy outcomes and multiple cancers risk in both mother and offspring were included. Evidence certainty was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. The protocol for this umbrella review was prospectively registered in PROSPERO (CRD42023470544). Results The search identified 129 meta-analyses of observational studies and 42 types of cancer. Moderate certainty of evidence, exhibiting statistical significance, has been observed linking per kilogram increase in birth weight to a heightened risk of breast cancer (OR = 1.07, 95% CI = 1.02–1.12), prostate cancer (OR = 1.02, 95% CI = 1.00–1.05), leukemia (OR = 1.18, 95% CI = 1.13–1.23), and acute lymphoblastic leukemia in offspring (OR = 1.18, 95% CI = 1.12–1.23); rubella infection during pregnancy to an increased risk of leukemia in offspring (OR = 2.79, 95% CI = 1.16–6.71); and a linear dose–response association between an increase in the proportion of optimal birth weight and an elevated risk of acute lymphoblastic leukemia in offspring (OR = 1.16, 95% CI = 1.09–1.24), respectively. Conclusions Although some adverse pregnancy outcomes have clinically promising associations with risk of several cancers in both mother and offspring, it is essential to conduct additional research to solidify the evidence, evaluate causality, and ascertain clinical utility.

Abstract Background Controlled ovarian stimulation is a common skill of assisted reproductive technologies (ARTs). In the clinic, some females would undergo more than one controlled ovarian stimulation cycle. However, few studies have focused on the influence of multi-superovulation on oocytes and offspring. Results Here, we found that multi-superovulation disrupted the transcriptome of oocytes and that the differentially expressed genes (DEGs) were associated mainly with metabolism and fertilization. The disruption of mRNA degradation via poly (A) size and metabolism might be a reason for the reduced oocyte maturation rate induced by repeated superovulation. Multi-superovulation results in hypo-genomic methylation in oocytes. However, there was an increase in the methylation level of CGIs. The DMRs are not randomly distributed in genome elements. Genes with differentially methylated regions (DMRs) in promoters are enriched in metabolic pathways. With increasing of superovulation cycles, the glucose and insulin tolerance of offspring is also disturbed. Conclusions These results suggest that multi-superovulation has adverse effects on oocyte quality and offspring health.

Abstract Lung cancer is intricately associated with genetic susceptibility, leading to familial clustering among affected individuals. This cross-sectional study aimed to assess the knowledge, attitude, and practice (KAP) toward lung cancer risk among the offspring of lung cancer patients. This study was conducted at Guangdong Provincial People’s Hospital between April 2023 and August 2023. Participants’ demographic characteristics and KAP toward lung cancer risk were collected through questionnaires. A total of 481 valid questionnaires were enrolled, with 243 (50.52%) males, and 242 (50.31%) aged > 40 years old. The mean scores for knowledge, attitude, and practice were 8.54 ± 2.60 (range: 0–13), 25.93 ± 3.16 (range: 7–35), and 17.47 ± 4.30 (range: 5–25), respectively. Structural equation modeling indicated that knowledge exerted a negative direct effect on attitude (β = − 0.417, P = 0.006) but a positive direct effect on practice (β = 0.733, P = 0.025). Additionally, attitudes displayed a negative direct effect on practice (β = − 1.707, P = 0.002). In conclusion, offspring of lung cancer patients exhibited insufficient knowledge, positive attitude, and suboptimal practice toward lung cancer risk.

Objective This study aimed to assess whether in utero exposure to hyperglycemia influences prescription medicine purchases in the offspring of women with type 1 diabetes (exposed offspring).Patients/materials and methods We identified all singleton exposed offspring born in the hospital district of Helsinki and Uusimaa, Finland, between 1988 and 2011 from the Finnish Medical Birth Register, maintained by the Finnish Institute for Health and Welfare. For each exposed offspring, we obtained five age- and province-matched offspring of women without diabetes (reference offspring), from the Finnish Medical Birth Register. By combining data from three national registers, this longitudinal cohort study assessed prescription medicine purchases in exposed offspring (n = 1,725) and reference offspring (n = 8,755) from seven to thirty years of age. Prescription medicine purchases were grouped according to the Anatomical Therapeutic Chemical (ATC) classification system.Results Between 1995 and 2018, a total of 211,490 prescription medicines were purchased. After a median follow-up of 10.9 (interquartile range 4.9,17.6) years, we observed higher incidence risk ratios (IRR) of prescription medicine purchases for several ATC main groups in exposed offspring compared to reference offspring, with the highest IRR of 4.06 (95% CI: 2.78 to 5.94) for medicines affecting metabolism (e.g. diabetes medicines).Conclusion Our findings suggest that exposed offspring purchase more reimbursable prescription medicines than reference offspring from age seven to thirty years. More research is needed to examine the effects of intrauterine exposure to hyperglycemia on long-term health in offspring.

Abstract This study aimed to investigate the association of lipid profile in early pregnancy and the risk of congenital heart disease (CHD) in offspring. This study was a prospective cohort design based on the Fujian Birth Cohort Study in China. We recruited pregnant women at ≤ 14 weeks of gestation between 2019 and 2022, and all participants in this study filled out the questionnaire about periconceptional exposure. Simultaneously, we collected participants’ fasting blood samples to measure their lipid profile by automatic biochemical analyzer. The outcome was defined as offspring with CHD. A multivariable logistic regression model was used to calculate adjusted odds ratio (AOR) risk estimates, which indicate the associations between maternal lipid profiles and CHD in offspring. Restricted cubic splines were used to estimate their nonlinear relationship. A total of 21,425 pregnant women with an average gestational age of 11.3 (± 1.40) weeks were included in the analysis. The higher triglyceride (AOR 1.201, 95% CI [1.036, 1.394]), low-density lipoprotein (AOR 1.216, 95% CI [1.048, 1.410]), apolipoprotein B (Apo B) (AOR 2.107, 95% CI [1.179, 3.763]) levels were correlated with increased odds of CHD in offspring, while high-density lipoprotein (OR 0.672, 95% CI [0.490, 0.920]) related with decreased odds of CHD in offspring. The restricted cubic spline suggested a nonlinear relationship between total cholesterol (TC) levels and the risk of CHD in offspring (P = 0.0048), but no significant nonlinear relationships were found in other lipid profile. Apolipoprotein A was not related to the risk of CHD in offspring as either a continuous variable or a hierarchical variable. Elevated lipid profile in early pregnancy levels are associated with an increased risk of CHD in offspring. Additionally, there is a non-linear relationship between TC levels and the risk of CHD in offspring.

Abstract Background Cadmium (Cd) exposure has been found to have detrimental effects on the development of the central nervous system and cognitive ability in children. However, there is ongoing debate regarding the impact of maternal Cd exposure on the cognitive ability of offspring. In this study, we aimed to investigate the mechanisms underlying the influence of maternal Cd exposure on the cognitive ability of offspring rats. Methods Here, we constructed a model of cadmium poisoning in first-generation rats through gavage. The cognitive and memory abilities of its offspring were evaluated by water maze experiment. Then, we used the gene chip to find out the key genes, and we performed qRT-PCR detection of these genes. Subsequently, enrichment analysis was employed to identify pathways. Finally, we constructed a co-expression network consisting of LncRNAs and mRNAs to elucidate the biological functions and regulatory mechanisms of LncRNAs. Results The results of the water maze trial demonstrated that the offspring of rats exposed to cadmium in the first generation had reduced cognitive and memory abilities. Through an analysis of gene expression in the hippocampus of the cadmium-treated rats' offspring and the control group, we identified a correlation between the islet secretion pathway and the cognitive impairment observed in the offspring. Utilizing various algorithms, we identified Cpa1 and Prss1 as potential key genes associated with the cognitive impairment caused by cadmium. The results of qRT-PCR demonstrated a decrease in the expression levels of these genes in the hippocampus of the cadmium-treated rats’ offspring. In addition, in the co-expression network, we observed that Cpa1 was co-expressed with 11 LncRNAs, while Prss1 was associated with 4 unexplored LncRNAs. Furthermore, we conducted an analysis to examine the relationship between Cpa1, Prss1-related transcription factors, and LncRNAs. Conclusion Overall, this study provides novel insights into the molecular effects of first generation Cd exposure on the cognitive ability of offspring. The target genes and signaling pathways investigated in this study could serve as potential targets for improving neurodevelopment and cognitive ability in children.

Background: We investigate the role of galantamine on autonomic dysfunction associated with early cardiometabolic dysfunction in the offspring of fructose-overloaded rats. Methods: Wistar rats received fructose diluted in drinking water (10%) or water for 60 days prior to mating. Fructose overload was maintained until the end of lactation. The offspring (21 days after birth) of control and fructose-overloaded animals were divided into three groups: control (C), fructose (F) and fructose + galantamine (GAL). GAL (5 mg/kg) was administered orally until the offspring were 51 days old. Metabolic, hemodynamic and cardiovascular autonomic modulation were evaluated. Results: The F group showed decreased insulin tolerance (KITT) compared to the C and GAL groups. The F group, in comparison to the C group, had increased arterial blood pressure, heart rate and sympathovagal balance (LF/HF ratio) and a low-frequency band of systolic arterial pressure (LF-SAP). The GAL group, in comparison to the F group, showed increased vagally mediated RMSSD index, a high-frequency band (HF-PI) and decreased LF/HF ratio and variance in SAP (VAR-SAP) and LF-SAP. Correlations were found between HF-PI and KITT (r = 0.60), heart rate (r = −0.65) and MAP (r = −0.71). Conclusions: GAL treatment significantly improved cardiovascular autonomic modulation, which was associated with the amelioration of cardiometabolic dysfunction in offspring of parents exposed to chronic fructose consumption.

Abstract Background In utero exposure to maternal hyperglycemia has been associated with an increased risk for the development of chronic diseases in later life. These predispositions may be programmed by fetal DNA methylation (DNAm) changes that persist postnatally. However, although some studies have associated fetal exposure to gestational hyperglycemia with DNAm variations at birth, and metabolic phenotypes in childhood, no study has yet examined how maternal hyperglycemia during pregnancy may be associated with offspring DNAm from birth to five years of age. Hypothesis Maternal hyperglycemia is associated with variation in offspring DNAm from birth to 5 years of age. Methods We estimated maternal hyperglycemia using the area under the curve for glucose (AUCglu) following an oral glucose tolerance test conducted at 24–30 weeks of pregnancy. We quantified DNAm levels in cord blood (n = 440) and peripheral blood at five years of age (n = 293) using the Infinium MethylationEPIC BeadChip (Illumina). Our total sample included 539 unique dyads (mother–child) with 194 dyads having DNAm at both time-points. We first regressed DNAm M-values against the cell types and child age for each time-point separately to account for the difference by time of measurement for these variables. We then used a random intercept model from the linear mixed model (LMM) framework to assess the longitudinal association between maternal AUCglu and the repeated measures of residuals of DNAm. We adjusted for the following covariates as fixed effects in the random intercept model: maternal age, gravidity, smoking status, child sex, maternal body mass index (BMI) (measured at first trimester of pregnancy), and a binary variable for time-point. Results In utero exposure to higher maternal AUCglu was associated with lower offspring blood DNAm levels at cg00967989 located in FSD1L gene (β = − 0.0267, P = 2.13 × 10–8) in adjusted linear regression mixed models. Our study also reports other CpG sites for which DNAm levels were suggestively associated (P

Objective To systematiclly evaluate the relationship between assisted reproductive technology（ART） and autism spectrum disorders（ASD） in their offspring. Methods Systematic searches of PubMed, Web of Science, CBM, VIP, and CNKI databases were conducted to collect the cohort studies on ASD in ART progeny published from database establishment to April 1, 2022. After four independent reviewers screened the literature, extracted the data and assessed their quality with Newcastle-Ottawa scale（NOS）, a Meta-analysis was performed using Stata 15.1 software. Results Finally, 8 articles were included to assess the risk of ASD in 335507 offspring after ART（ART group） and 14233258 offspring of natural conception（NC group）. After excluding one study with greater heterogeneity by sensitivity analysis,the incidence of child with ASD in ART group was significantly higher than that in NC group（RR=1.06, 95%CI1.01-1.11, P

Background With the aggravation of aging trend, the influence of intergenerational support on the health of the elderly has gradually attracted attention, and the absence of spiritual care and life care is an important factor for the occurrence of health problems in the elderly, but there is a lack of scientific evaluation tools to evaluate the cognitive level of old-age care. Objective To develop a Knowledge, Attitude and Practice about Filial Piety Ethics Questionnaires for Offspring and Grandchildren in the process of elderly care, and to test its reliability and validity. Methods From April to July 2021, the first draft of the questionnaire was determined by searching relevant contents in databases such as PubMed, Web of Science, China Knowledge Network and Wanfang Data Knowledge Service Platform, and using the theory of knowledge, attitude and practice and Maslow's hierarchy of needs as the theoretical framework, combined with literature review, national maintenance laws, qualitative interviews, the questionnaire was refined with results of the Delphi expert consensus and pre-survey. From October 2021 to March 2022, 270 subjects from each generation were selected for the formal survey and 50 subjects from the offspring and 38 subjects from the grangchildren were selected for test-retest reliability using the random cluster sampling method. A total of 540 questionnaires were distributed, 270 questionnaires for each generation. A total of 528 valid questionnaires were returned, 264 valid questionnaires for each generation, with a valid return rate of 97.8%. Its reliability and validity were analyzed to determine the final questionnaire entry. Results The Knowledge, Attitude and Practice about Filial Piety Ethics Questionnaires for Offsprings included 3 dimensions and 34 items. Exploratory factor analysis produced 3 factors, with a cumulative variance contribution rate of 64.455%. The content validity of each item ranged from 0.867 to 1.000, and the average content validity of the questionnaire was 0.967. Cronbach's α coefficient was 0.953, split-half reliability was 0.811, and test-retest reliability was 0.987. The Knowledge, Attitude and Practice about Filial Piety Ethics Questionnaires for Grandchildren consisted of 31 items in 3 dimensions. Exploratory factor analysis produced three factors, the cumulative variance contribution rate was 64.641%; the content validity of each item ranged from 0.867 to 1.000, the average content validity of the questionnaire was 0.964; Cronbach's α coefficient was 0.952, split-half reliability was 0.837, and test-retest reliability was 0.991. Conclusion The developed questionnaire has good reliability and validity, and can be used as a research tool to evaluate the current status of filial piety ethic knowledge, attitude and behavior of offsprings and grandchildren in the process of elderly care.

Abstract Background Maternal hypertensive disorders during pregnancy (HDP) have been suggested to contribute to the development of offspring cardiovascular disease later in life, but empirical evidence remains inconsistent. This study was aimed to assess the association of maternal overall and type-specific HDPs with diabetes in offspring from childhood to early adulthood. Methods Using Danish national health registers, a total of 2,448,753 individuals born in Denmark from 1978 to 2018 were included in this study. Maternal HDP included chronic hypertension, gestational hypertension, and preeclampsia. The outcome of interest was diabetes in offspring (including type 1, type 2, and gestational diabetes). The follow-up of offspring started at birth and ended at the first diagnosis of diabetes, emigration from Denmark, death, or time end on 31 December 2018, whichever came first. Cox proportional hazards regression was used to evaluate the hazard ratios (HRs) with 95% confidence intervals (CIs) of the association between maternal HDP and diabetes (including type 1, type 2, and gestational diabetes) in offspring from birth to young adulthood (up to 41 years), with the offspring’s age as the time scale. Results During a follow-up of up to 41 (median: 19.3) years, 1247 offspring born to mothers with HDP and 23,645 offspring born to mothers without HDP were diagnosed with diabetes. Compared with offspring born to mothers without HDP, those born to mothers with HDP had an increased risk for overall diabetes (HR=1.27, 95% CI=1.20–1.34), as well as for type 2 diabetes (HR=1.57, 95% CI=1.38–1.78) and gestational diabetes (HR=1.37, 95% CI=1.25–1.49). We did not observe obvious increased risk for type 1 diabetes (HR=1.08, 95% CI=0.98–1.18). Offspring of mothers with gestational hypertension (HR=1.37, 95% CI=1.00–1.88) or preeclampsia (HR=1.62, 95% CI=1.41–1.87) had higher risks of type 2 diabetes. The strongest association was observed for severe preeclampsia, with a 2-fold risk of type 2 diabetes (HR=2.00, 95% CI=1.42–2.82). The association between maternal HDP and type 1 diabetes did not reach statistical significance, except for maternal gestational hypertension (HR=1.41, 95%CI=1.17–1.71). In addition, we found that offspring born to mothers with any subtypes of maternal HDP had higher risk of gestational diabetes, and the corresponding HRs (95%CIs) for chronic hypertension, gestational hypertension, and preeclampsia were 1.60 (1.06–2.41), 1.29 (1.04–1.59), and 1.38 (1.24–1.53), respectively. We also observed stronger associations among offspring of mothers with HDP and comorbid diabetes (HR=4.64, 95%CI=3.85–5.60) than offspring of mothers with HDP or diabetes alone. Conclusions Offspring of mothers with HDP, especially mothers with comorbid diabetes, had an increased risk of diabetes later in their life. Our findings suggest that timely and effective prevention of HDP in women of childbearing age should be taken into consideration as diabetes prevention and control strategies for their generations.

Introduction: Follow-up of the mothers and their offspring recruited to a randomized controlled trial comparing neonatal outcomes in women with gestational diabetes treated with metformin or glibenclamide was conducted 9 years ago. A significant decrease in neonatal hypoglycemia in the group treated with metformin was seen in the original study. Methodology: Results of clinical examination, blood sample collection, and dual-energy X-ray absorptiometry (DEXA) scan not published in a brief communication are described in this study. The nutritional status was assessed using a 3-day recall method using the Indian Food Composition Table 2017. The physical activity of offspring was assessed using the Global Physical Activity Questionnaire. Results: The overall follow-up rate of the cohort was 49% and similar in both the groups. The anthropometric details, blood tests, and DEXA in the women and their offspring were similar except that the offspring of the group on metformin had higher triglyceride values than the offspring of the women treated with glibenclamide. The average body mass index of the offspring was similar and was 18. Currently, women who were treated with glibenclamide 9 years ago had higher fasting plasma glucose levels (9.2 [7.3, 12.6]) than the metformin group (7.2 [6.1, 8.4] median [interquartile range]), P = 0.02. They also had significantly higher diastolic blood pressure readings 77.1mmHg (8.9) and 72.1mmHg (11.7) mean (SD), P = 0.035. (Information from the previously published brief communication). Conclusion: No significant adverse outcome was seen in women treated with metformin and the offspring 9 years later.

Background: More than 50% of patients with diabetes mellitus in India are unaware about their diabetic status. Pre-diabetes is a potential state for developing diabetes mellitus. Methods: The present cross-sectional hospital based observational study aimed to screen apparently healthy offspring of patients known to have type 2 diabetes mellitus (T2DM) in Western Maharashtra region in India. The study was conducted in 187 offspring of T2DM patients between the age group of 18–50 years. Fasting blood glucose levels were tested in all of them. Results: Among offspring of T2DM patients, pre-diabetes was documented in 20.9% (14.4% in males, 6.4% in females). In the age group of 41–50 years, pre-diabetes was evident in 27.8% which was high compared with other age groups. Prediabetes among offspring with father with T2DM, mother with T2DM and both parents with T2DM were 10.7%, 30.3% respectively 23.5%. Conclusions: Our observations suggest that an association exists between positive family history of T2DM and pre-diabetes in Western Maharashtra. Screening offspring of patients with T2DM may be useful as a public health tool for early detection of T2DM.

Introduction Systemic lupus erythematosus (SLE) is a prototypic autoimmune disorder with a variable clinical course, ranging from mild to severe forms. It mainly occurs in women, especially those of fertile age. The aim of the study was to systematically analyze the associations of perinatal disease activity with adverse outcomes of Chinese patients with SLE and their off-spring. Material and methods Data of prenatal SLE patients and healthy pregnant woman admitted to our hospital during the period October 2001 to January 2018 were retrospectively collected, and the status of offspring of SLE patients was followed up in March 2020. Disease activity was evaluated by SLE disease activity index 2000 (SLEDAI-2k), and those with scores > 6 were defined as having active disease. Results In total, 198 deliveries of 194 SLE patients and 199 deliveries of healthy women were documented. Maternal and fetal adverse outcomes occurred in 74 (37.4%) and 90 (45.5%) deliveries of SLE patients, respectively, which were significantly higher than those of healthy subjects. Among SLE patients, the active group had higher rates of gestational hypertension (p < 0.001), reeclampsia/eclampsia (p < 0.001), low birth weight (p < 0.001), premature birth (p < 0.001) and fetal growth restriction (FGR) (p < 0.01) than the inactive group. Multivariate logistic analysis revealed that perinatal renal activity was associated with gestational hypertension (OR 4.43, p < 0.001), preeclampsia/ eclampsia (OR 9.14, p < 0.001), low birth weight (OR 2.24, p < 0.05) and premature birth (OR 4.20, p < 0.001). Compared with the general population, offspring of SLE patients had relatively high rates of eczema (50/142, 35.2%) and congenital heart disease (6/142, 4.2%), which were irrelevant to perinatal disease activity, but related to specific antibodies. Conclusions For perinatal women with SLE, renal activity is associated with a variety of adverse pregnancy outcomes. However, maternal perinatal dis�ease activity does not seem to affect the growth of their offspring

Highlights Pancreatic insulin production was reduced in adult male offspring born to reduced uteroplacental perfusion (RUPP) rats. Offspring born to RUPP dams exhibited sex-specific alterations in insulin, ghrelin and glucagon changes.

Abstract Background Parental depression is associated with a range of mental health conditions and other difficulties in the offspring. Nevertheless, some offspring exposed to parental depression do not develop mental health problems, indicating the presence of protective factors that may buffer parental depression-related risk effects. However, evidence of protective factors that might explain good sustained mental health in offspring of depressed parents is limited and systematic synthesis of these factors is still needed. Therefore, as far as we are aware, this will be the first systematic review that will identify parent, family, child, social, and lifestyle factors associated with mental health resilience in offspring of depressed parents, examine evidence for sex-, developmental stage-, and outcome-specific factors and define mental health resilience in the parental depression context. Methods This protocol has been developed according to the PRISMA-P guidelines. Electronic searches will be performed for articles published up to 2022 in PsycINFO, Embase, MEDLINE, Web of Science Core Collection, and Cochrane Library. Two reviewers will independently screen titles/abstracts and full-texts against eligibility criteria, extract the data, and assess the overall quality of evidence. Both observational and RCT studies will be eligible for inclusion if they report offspring mental health resilience/outcome and depressive symptoms or depressive disorder in at least one of the parents/caregivers. Risk of bias will be assessed using The Joanna Briggs Institute (JBI) critical appraisal checklists and The Revised Cochrane risk of bias tool for randomised trials (RoB 2). It is expected that studies will be heterogeneous; therefore, meta-analysis will not be attempted. Studies will be systematically retrieved and collated using numerical, graphical, tabular, and narrative summaries and grouped by their design, scope, or overall quality. Further sub-group analyses will be performed to examine sex-, developmental stage-, and outcome-specific protective factors. Discussion The proposed systematic review will be the first to summarise and critically assess quality and strength of evidence of protective factors associated with mental health resilience in offspring of depressed parents. Directions and effect sizes of the protective factors will be discussed as well as differences between the studies, their limitations, and research gaps and future directions. Strengths and limitations of the proposed systematic review will be also discussed. The proposed systematic review findings are expected to help better understand mental health resilience and identify targets for evidence-based prevention and intervention strategies for those in need. Systematic review registration A previous version of this systematic review protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO) database ( www.crd.york.ac.uk/PROSPERO , CRD42021229955).

Physical development of offspring can be an important criterion applied to assess effects produced by parental exposure. The cohort that includes workers employed at Mayak Production Association (PA), the first nuclear fuel cycle production facility in Russia, is a valuable information source for analyzing consequences of occupational exposure. Our objective was to analyze somatometric parameters of newborn children of Mayak PA workers who were occupationally exposed to pre-conception external gamma-radiation. We retrospectively analyzed anthropometric measurements of 13,880 newborn children, all born in 1949–1973; 9321 children were conceived by parents who were long-term occupationally exposed to radiation at Mayak PA. The analysis covered the core anthropometric elements including height, weight, head circumference, and chest circumference. Development proportionality was estimated by using Quetelet, Vervek – Vorontsov’s, and Erismann indexes. We estimated a correlation between anthropometric measurements and accumulated parental pre-conception external gamma radiation dose and calculated relative risk coefficients and odds ratio with 95 % confidence interval. We established that parents were exposed to a wide range of external gamma radiation doses, up to 4075.6 mGy to the ovaries and 5653.1 mGy to the testicles. There was a weak correlation between newborns’ height and weight and parental exposure. We also detected a trend for a decrease in newborns’ body mass with increasing accumulated pre-conception dose of external gamma radiation to the ovaries and, conversely, for an increase in it with a growing dose to the testicles. We revealed a statistically significant increase in height and weight among children conceived and born by Mayak PA workers, namely, a greater share of children with high body mass at birth. Analysis of children’s somatotypes confirmed excessive values of proportionality indexes that showed height and weight measurements among children of exposed parents. Additional analysis of firstborns and children with proper duration of gestation produced the same results. Risk assessment indicated there was significant prevalence of children with high body mass among offspring of exposed people. We also assessed physical development of Mayak PA workers’ newborns taking into account the latest data on long-term occupational exposure; this assessment is vital for epidemiological monitoring over health of children born by personnel employed at radiation-hazardous production facilities.

Dietary nutrients are the key determinants of the lifespan and metabolic health. The content of specific dietary compounds in the parental diet can epigenetically affect the physiological state of the offspring. Here, we studied how variable dietary protein content in the diet of parental generation affects antioxidant capacity of Drosophila melanogaster adult offspring. The dry yeast concentration ranging from 0.25% to 15% in the parental diet was the only variable in the experiments, whereas subsequent generation was kept on a diet of the same composition. We found, that flies fed with yeast-restricted (0.25%) diet produced F1 male flies with a higher cold tolerance and higher activity of the second-line antioxidant enzymes whereas in F1 females no effect of parental diet composition on the cold tolerance, catalase, GST, G6PDH, IDH activity and low thiols content was detected. The results suggest that nutrient-dependent changes of genes expression in the flies of paternal generation differently affect the stress response of males and females of the first-generation offspring.

Abstract Background Greater maternal adiposity before or during pregnancy is associated with greater offspring adiposity throughout childhood, but the extent to which this is due to causal intrauterine or periconceptional mechanisms remains unclear. Here, we use Mendelian randomisation (MR) with polygenic risk scores (PRS) to investigate whether associations between maternal pre-/early pregnancy body mass index (BMI) and offspring adiposity from birth to adolescence are causal. Methods We undertook confounder adjusted multivariable (MV) regression and MR using mother-offspring pairs from two UK cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) and Born in Bradford (BiB). In ALSPAC and BiB, the outcomes were birthweight (BW; N = 9339) and BMI at age 1 and 4 years (N = 8659 to 7575). In ALSPAC only we investigated BMI at 10 and 15 years (N = 4476 to 4112) and dual-energy X-ray absorptiometry (DXA) determined fat mass index (FMI) from age 10–18 years (N = 2659 to 3855). We compared MR results from several PRS, calculated from maternal non-transmitted alleles at between 29 and 80,939 single nucleotide polymorphisms (SNPs). Results MV and MR consistently showed a positive association between maternal BMI and BW, supporting a moderate causal effect. For adiposity at most older ages, although MV estimates indicated a strong positive association, MR estimates did not support a causal effect. For the PRS with few SNPs, MR estimates were statistically consistent with the null, but had wide confidence intervals so were often also statistically consistent with the MV estimates. In contrast, the largest PRS yielded MR estimates with narrower confidence intervals, providing strong evidence that the true causal effect on adolescent adiposity is smaller than the MV estimates (P difference = 0.001 for 15-year BMI). This suggests that the MV estimates are affected by residual confounding, therefore do not provide an accurate indication of the causal effect size. Conclusions Our results suggest that higher maternal pre-/early-pregnancy BMI is not a key driver of higher adiposity in the next generation. Thus, they support interventions that target the whole population for reducing overweight and obesity, rather than a specific focus on women of reproductive age.

Background: Offspring of hypertensive parents have been reported to have alteration on their sympathovagal balance and have exaggerated response to stressful conditions. Many Christians observe a period of fasting at the beginning of every year, which imposes some stress on their bodies. Objective: This study aims to investigate the effect of 21-day intermittent fasting on some cardiovascular parameters in offspring of hypertensive and normotensive parents. Materials and Methods: Eighty young adults (20–28 years) were divided into equal number of male and female offspring of hypertensive and normotensive parents based on questionnaire. Their body weight, height, waist circumference (WC), body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were recorded 1 week before the fasting period began and then weekly for 3 weeks, in which they fasted. Results: The weight, BMI, and WC reduced during fasting, but the reductions were not significant (P > 0.05). The SBP and DBP were higher in male offspring of hypertensive parents than all other groups. SBP was also significantly (P < 0.05) higher in males than females before fast and during fast. Fasting significantly reduced the SBP in the male offspring of both hypertensive and normotensive parents. The HR reduced in the females during fast but increased from a lower level in males to a value not significantly different from prefasting level. Conclusion: Fasting reduces the high SBP and DBP in male offspring of hypertensive parents, which is beneficial to their cardiovascular system.

Abstract Background The associations of maternal cigarette smoking with congenital anomalies in offspring have been inconsistent. This study aimed to clarify the associations of the timing and intensity of maternal cigarette smoking with 12 subtypes of birth congenital anomalies based on a nationwide large birth cohort in the USA. Methods We used nationwide birth certificate data from the US National Vital Statistics System during 2016–2019. Women reported the average daily number of cigarettes they consumed 3 months before pregnancy and in each subsequent trimester during pregnancy. Twelve subtypes of congenital anomalies were identified in medical records. Poisson regression analysis was used to estimate the risk ratios (RRs) with 95% confidence intervals (CIs) for 12 subtypes of congenital anomalies associated with the timing (i.e., before pregnancy, and during three different trimesters of pregnancy) and intensity (i.e., number of cigarettes consumed per day) of maternal cigarette smoking. Results Among the 12,144,972 women included, 9.3% smoked before pregnancy and 7.0%, 6.0%, and 5.7% in the first, second, and third trimester, respectively. Maternal smoking before or during pregnancy significantly increased the risk of six subtypes of birth congenital anomalies (i.e., congenital diaphragmatic hernia, gastroschisis, limb reduction defect, cleft lip with or without cleft palate, cleft palate alone, and hypospadias), even as low as 1–5 cigarettes per day. The adjusted RRs (95% CIs) for overall birth congenital anomalies (defined as having any one of the congenital malformations above significantly associated with maternal cigarette smoking) among women who smoked 1–5, 6–10, and ≥ 11 cigarettes per day before pregnancy were 1.31 (1.22–1.41), 1.25 (1.17–1.33), and 1.35 (1.28–1.43), respectively. Corresponding values were 1.23 (1.14–1.33), 1.33 (1.24–1.42), 1.33 (1.23–1.43), respectively, for women who smoked cigarettes in the first trimester; 1.32 (1.21–1.44), 1.36 (1.26–1.47), and 1.38 (1.23–1.54), respectively, for women who smoked cigarettes in the second trimester; and 1.33 (1.22–1.44), 1.35 (1.24–1.47), and 1.35 (1.19–1.52), respectively, for women who smoked cigarettes in the third trimester. Compared with women who kept smoking before and throughout pregnancy, women who never smoked had significantly lower risk of congenital anomalies (RR 0.77, 95% CI 0.73–0.81), but women who smoked before pregnancy and quitted during each trimester of pregnancy had no reduced risk (all P > 0.05). Conclusions Maternal smoking before or during pregnancy increased the risk of several birth congenital anomalies, even as low as 1–5 cigarettes per day. Maternal smokers who stopped smoking in the subsequent trimesters of pregnancy were still at an increased risk of birth congenital anomalies. Our findings highlighted that smoking cessation interventions should be implemented before pregnancy.

Abstract At the dawn of the twentieth century, the medical care of mothers and children was largely relegated to family members and informally trained birth attendants. As the industrial era progressed, early and key public health observations among women and children linked the persistence of adverse health outcomes to poverty and poor nutrition. In the time hence, numerous studies connecting genetics (“nature”) to public health and epidemiologic data on the role of the environment (“nurture”) have yielded insights into the importance of early life exposures in relation to the occurrence of common diseases, such as diabetes, allergic and atopic disease, cardiovascular disease, and obesity. As a result of these parallel efforts in science, medicine, and public health, the developing brain, immune system, and metabolic physiology are now recognized as being particularly vulnerable to poor nutrition and stressful environments from the start of pregnancy to 3 years of age. In particular, compelling evidence arising from a diverse array of studies across mammalian lineages suggest that modifications to our metagenome and/or microbiome occur following certain environmental exposures during pregnancy and lactation, which in turn render risk of childhood and adult diseases. In this review, we will consider the evidence suggesting that development of the offspring microbiome may be vulnerable to maternal exposures, including an analysis of the data regarding the presence or absence of a low-biomass intrauterine microbiome.

Relevance. Fulvestrant is used for the treatment of breast cancer in combination with other drugs. The aim of the study was to determine the effect of the prenatal action of fulvestrant on the ovaries of the offspring of laboratory mice. Materials and Methods. The experimental animals were divided into 4 groups: intact, control and 2 experimental, 5 animals in each group. Injections were administered to females after fertilization at the gestational stage E 11.5 once intramuscularly. In the control group (n=5), sterile castor oil was administered at a dose of 0.8 mcg/kg. In the first experimental group (n=5), an antiestrogen was introduced in the form of an oil solution of fulvestrant 0.08 ml 0.0005% at a dose of 20 mcg/kg. In the second group (n=5), an antiestrogen was introduced in the form of an oil solution of fulvestrant 0.4 ml 0.0005% at a dose of 100 mcg/kg. Results and Discussion . The study revealed that in the ovaries when the drug was administered at a dose of 20 mcg/kg (F-20), the number of primordial follicles was reduced. Accordingly, the number of follicles of subsequent generations decreased. With the introduction of the drug fulvestrant 100 mcg/kg (F-100) on the section of the ovary, sclerosis of the stromal component is observed, accompanied by a rearrangement of the vascular network with signs of atresia and cystic degeneration of the follicular epithelium in the secondary and tertiary follicles, formed cysts are observed in the ovarian parenchyma. Conclusion. The prenatal effect of the drug fulvestrant on the maternal body during pregnancy leads to persistent structural changes in the ovaries of the offspring, manifested in the late stages of ontogenesis, which, in turn, can lead to violations of reproductive function. The depth and scale of these changes are dose-dependent.

Parental dietary nutrients epigenetically influence offspring metabolism. Our analysis revealed unforeseen patterns in how enzymes of the main metabolic pathways respond to protein content in the diet. We reared parental flies Drosophila melanogaster on four types of diet with different dry yeast concentrations ranging from 0.25% to 15%. The subsequent generation was fed by the same diet, so the only variable in the experiments was the yeast concentration in the parental diet. We showed that protein restriction in the parental diet led to higher lactate dehydrogenase (LDH) activity in parents, and this effect was inherited in their progeny. The transgenerational effect of parental dietary yeast on malate dehydrogenase (MDH) activity was found only in males. An elevated level of dietary yeast was sufficient to enhance alanine transaminase ( ALT) and aspartate transaminase (AST) activity in parents, however, did not affect ALT activity and decreased AST in their offspring. A low yeast parental diet was shown to cause higher urea content in F1 males. It is concluded that parental dietary yeast plays a critical role in metabolic health that can be inherited through generation.Parental dietary nutrients epigenetically influence offspring metabolism. Our analysis revealed unforeseen patterns in how enzymes of the main metabolic pathways respond to protein content in the diet. We reared parental flies Drosophila melanogaster on four types of diet with different dry yeast concentrations ranging from 0.25% to 15%. The subsequent generation was fed by the same diet, so the only variable in the experiments was the yeast concentration in the parental diet. We showed that protein restriction in the parental diet led to higher lactate dehydrogenase (LDH) activity in parents, and this effect was inherited in their progeny. The transgenerational effect of parental dietary yeast on malate dehydrogenase (MDH) activity was found only in males. An elevated level of dietary yeast was sufficient to enhance alanine transaminase ( ALT) and aspartate transaminase (AST) activity in parents, however, did not affect ALT activity and decreased AST in their offspring. A low yeast parental diet was shown to cause higher urea content in F1 males. It is concluded that parental dietary yeast plays a critical role in metabolic health that can be inherited through generation.

Background Numerous studies have shown that exposure to prenatal maternal stress (PMS) is associated with various psychopathological outcomes of offspring. The accumulating evidence linking bacteria in the gut and neurons in the brain (the microbiota-gut-brain axis) has been aconsensus; however, there is a lack of research on the involvement mechanism of gut microbiota in the regulation of the BDNF/CREB signaling pathway in the hippocampus of prenatally stressed offspring. Methods Pregnant rats were subjected to chronic unpredictable mild stress (CUMS) to establish the prenatal maternal stress model. The body weight was measured and the behavioral changes were recorded. Offspring were tested to determine emotional state using sucrose preference test (SPT), open-field test (OFT) and suspended tail test (STT). Gut microbiota was evaluated by sequencing the microbial 16S rRNA V3–V4 region, and the interactive analysis of bacterial community structure and diversity was carried out. The expression of hippocampal BDNF, TrkB and CREB mRNA and proteins were respectively measured using RT-PCR and Western blotting. Results Prenatal maternal stress increased maternal plasma corticosterone levels, slowed maternal weight gain and caused depression-like behaviors (all P < 0.05). In offspring, prenatal maternal stress increased plasma corticosterone levels (P < 0.05) and emotional behavior changes (depression-like state) were observed (P < 0.05). The species abundance, diversity and composition of the offspring’s gut microbiota changed after the maternal stress during pregnancy (P < 0.05). Compared with the control group’s offspring, the species abundance of Lactobacillaceae was dropped, while the abundance of the Muribaculaceae species abundance was risen. Concurrent, changes in the hippocampal structure of the offspring and decreases in expression of BDNF/CREB signaling were noted (P < 0.05). Conclusions Prenatal maternal stress leads to high corticosterone status and abnormal emotion behavior of offspring, which may be associated with the abnormal BDNF/CREB signaling in hippocampus of offspring caused by the change of gut microbiota composition.

Active smoking or passive entry of tobacco smoke into the body of a pregnant leads to the effects of nicotine on the fetus’s cells, which causes many problems of fetal development and health problems in the later life of the offspring. The researches made has conclusively proven that smoking during pregnancy contributes to the development of many endocrine disorders. The effect of tobacco smoke on the increase of leptin, C-reactive protein, decrease of adiponectin, as well as on the appearance of antibodies to islet cells of the pancreas, as the first step to the development of type 1 diabetes, was determined by epidemiological studies. In studying the effects of nicotine during lactation it was concluded that the consumption of 6 mg / kg / day of nicotine, hyperleptinemia and primary hypothyroidism develops in the newborn, and later in adulthood, all components of the metabolic syndrome. At the same time, the data on the effect of nicotine entering the mother's body and its further influence on the offspring’s thyroid gland are few. The objective: to the study histofunctional and morphometric features of the thyroid gland of both sexes offsprings born by mothers which were exposed to "passive" smoking during pregnancy. The study object: 6-month-old Wistar rats, first-generation offspring derived from control (intact) females that were exposed to tobacco smoke components in a reproduction model of "passive" smoking. Histological and morphometric changes of the thyroid gland of 6-month-old offspring of mothers in whose bodies the products of cigarette combustion entered through the respiratory tract were studied. Morphofunctional criteria of instability and changes in the microstructure of the thyroid gland of offsprings whose mothers were exposed to nicotine in postnatal life were determined. Primary apoptotic-destructive processes in parenchyma, the formation of unstructured cell fields and microfollicles allow us to consider these offsprings as a risk group for thyroid pathology in terms of additional exposure to negative factors of "passive" smoking.

Walnut (Juglans regia) from the Juglandaceae family contains high levels of omega 3 fatty acid, vitamin E and melatonin, hence its consumption is beneficial to would be mothers and their offspring. The current study was designed to determine the possible mechanism of walnut consumption by mothers during pregnancy and lactation and the positive effects on learning and memory processes in their offspring. Wistar adult female rats were placed into three groups: control (fed with pellet, 20 g daily during pregnancy and lactation), CASE 1 [fed with Walnut Kernel (WK) 6% of food intake during pregnancy and lactation] and CASE 2 (fed with WK, 9% of food intake during gestation and lactation). In order to evaluate offspring learning and memory, the Morris Water Maze (MWM) test was performed for their adult offspring at 80 days of age. Histological and molecular studies were utilized in order to discover the protective mechanism and efficacy of WK consumption. The results revealed that learning was significantly improved in the females of CASE 2, in comparison to controls, while there was no difference in memory among the different groups. In addition, the number of neurons significantly increased in the CASE 2 group compared to the control group. However, the molecular study demonstrated that there was no significant difference among the study groups. The results herein show that feeding mothers with WK may improve the learning competence of their pups and increase the number of neurons in both sexes.

Heavy fuel oil (HFO) spills pose serious threat to coastlines and sensitive resources. Stranded HFO that occurs along the coastline could cause long-term and massive damage to the marine environment and indirectly affect the survival of parental marine invertebrates. However, our understanding of the complex associations within invertebrates is primarily limited, particularly in terms of the toxicity effects on the offspring when parents are exposed to stranded HFO. Here, we investigated the persistent effects on the early development stage of the offspring following stranded HFO exposure on the sea urchin Strongylocentrotus intermedius. After 21 d exposure, sea urchins exhibited a significant decrease in the reproductive capacity; while the reactive oxygen species level, 3-nitrotyrosine protein level, protein carbonyl level, and heat shock proteins 70 expression in the gonadal tissues and gametes significantly increased as compared to the controls, indicating that HFO exposure could cause development toxicity on offspring in most traits of larval size. These results suggested that the stranded HFO exposure could increase oxidative stress of gonadal tissues, impair reproductive functions in parental sea urchins, and subsequently impact on development of their offspring. This study provides valuable information regarding the persistent toxicity effects on the offspring following stranded HFO exposure on sea urchins.

Background and purpose: Chronic stress has detrimental effects on reproductive system. Offspring are likely to be vulnerable to adverse effects from antipsychotic medication and stress transmitted through gonads and gametes. The present study aimed to investigate the fertility of female rats from male rats treated with sulpiride because of chronic physical or psychological stress. Materials and methods: In this experimental study, 36 adult male Wistar rats weighing 190±10 g were divided into six groups: control, sulpiride (the antagonist of dopamine D2 receptors) (4mg/kg,bw,ip), physical or psychological stress, and physical or psychological stress that received sulpiride. After 14 days, each male rat mated with three adult female rats. The female offspring of these rats were raised in normal conditions until adulthood. Then, the ovaries and body weight, and fertility of offspring were assessed using IVF. Results: The weight of the body and ovaries, percentage of egg cells, bicellular embryos, blastocysts, and hatched embryos after IVF, significantly reduced in offspring of stressed male rats compared with control group (P0.05), but administration of sulpiride significantly increased that in all groups compared with saline groups (P

ABSTRACT Clinical and subclinical hypothyroidism are the most common hormonal dysfunctions during pregnancy. Insufficient maternal thyroid hormones (THs) in the early stages of pregnancy can lead to severe impairments in the development of the central nervous system because THs are critical to central nervous system development. In the fetus and after birth, THs participate in neurogenic processes, cell differentiation, neuronal activation, axonal growth, dendritic arborization, synaptogenesis and myelination. Although treatment is simple and effective, approximately 30% of pregnant women in Brazil with access to prenatal care have their first consultation after the first trimester of pregnancy, and any delay in diagnosis and resulting treatment delay may lead to cognitive impairment in children. This review summarizes the effects of clinical and subclinical hypothyroidism on fetal neurodevelopment, behavior and cognition in humans and rodents. Arch Endocrinol Metab. 2020;64(1):89-95

Background and aim: General health is not merely the absence of illness or disability, but a state of well-being that enables one to cope with the stresses of life, become professionally and academically useful. Parentschr('39') multiple sclerosis complications have potential effects on the health of their offspring. Therefore, the aim of this study was to evaluate the effect of program based on Roy’s adaptation model on general health of offspring of patients with multiple sclerosis. Methods: This semi-experimental study was done on 80 offspring of parents with multiple sclerosis, member of the MS association and the welfare organization of Shahrekord in 2018. Samples were selected as available, Roy form were completed by them and those who scored less than 80%, entered the study. The general health questionnaire was completed in both groups before, after and two months after the intervention. In the intervention group, a program based Roy’s adaptation model was developed, implemented and followed up for six session (2session education, of general education and 4 session direct intervention). Data were analyzed by SPSS21 software and statistical tests. Results: Before intervention, the mean of general health scores between the two groups was not statistically significant (p = 0.716). But there was a significant difference immediately after (p = 0.025) and two months after the intervention (p

The aim was to characterize the association of maternal smoking trajectory during pregnancy with offspring’s smoking, alcohol and substance use behavior. We used the prospective Northern Finland Birth Cohort 1966 study including 11,653 mothers and their offspring followed up from mothers’ mid-pregnancy to age of 46 years. Main exposure was number of smoked cigarettes per day at each month of pregnancy. Outcome measures were offspring’s smoking, alcohol and drug use at age 14, starting age of smoking, ever-smoking, and smoked pack-years until age 46. Four maternal smoking trajectories during pregnancy were identified with latent class trajectory modelling, namely “non-smokers” (86.0% of mothers), “early quitters” (2.0%), “late quitters” (2.1%), and “consistent smokers” (9.9%). In comparison to non-smokers, all maternal smoking was associated with offspring’s increased odds of lifetime smoking adjusted for sex of the child, father’s smoking, occupational status and place of residence of family, marital status and mood of mother, and desirability of pregnancy. The consistent smoker’s class was associated with offspring’s number of smoked pack years by midlife (median [interquartile range]: 8.3 [1.4–17.4] vs. 4.8 [0.0–13.0], p = 0.028), and alcohol use in young age (odds ratio 1.23 [95% confidence interval 1.05–1.43]). Overall, to prevent parent-offspring transmission of smoking, the cessation support should target women planning pregnancy. Negative effects of maternal continuous smoking during pregnancy include all substance use and reach up to offspring’s middle age.

The aim was to detect correlations of IgG antibodies against N. caninum in serum and colostrum samples from ewes, through the IFAT, and to evaluate the presence of this immunoglobulin in the serum of newborn lambs after colostrum ingestion. Blood samples from 162 ewes that did not show any disease in the general physical examination and from their newborn lambs, not more than five days postpartum, along with 162 colostrum samples and 182 blood samples from the neonates, were analyzed. In total, 27.8% (45/162) of the mothers were positive for anti-N. caninum IgG, among which antibodies were detected in the colostrum in 46.7% (21/45). All the ewes with positive colostrum had reactive offspring. The kappa agreement for the correlation between the serological tests on the ewes and the colostrum results was 0.558. This correlation increased as the antibody titers of the mothers increased, and reached 1.000 from the titer of 1:400 from the mothers. Comparison of the antibody detection results between the offspring’s serum and colostrum showed a kappa agreement of 1.000. In conclusion, there was a good agreement regarding the detection of anti-N. caninum IgG between the colostrum samples and the lambs’ serum; the use of colostrum forms a noninvasive alternative for diagnosing N. caninum in sheep herds.

Abstract Background Maternal blood folate concentrations during pregnancy have been previously linked with DNA methylation patterns, but this has been done predominantly through observational studies. We showed recently in an epigenetic analysis of the first randomized controlled trial (RCT) of folic acid supplementation specifically in the second and third trimesters (the EpiFASSTT trial) that methylation at some imprinted genes was altered in cord blood samples in response to treatment. Here, we report on epigenome-wide screening using the Illumina EPIC array (~ 850,000 sites) in these same samples (n = 86). Results The top-ranked differentially methylated promoter region (DMR) showed a gain in methylation with folic acid (FA) and was located upstream of the imprint regulator ZFP57. Differences in methylation in cord blood between placebo and folic acid treatment groups at this DMR were verified using pyrosequencing. The DMR also gains methylation in maternal blood in response to FA supplementation. We also found evidence of differential methylation at this region in an independent RCT cohort, the AFAST trial. By altering methylation at this region in two model systems in vitro, we further demonstrated that it was associated with ZFP57 transcription levels. Conclusions These results strengthen the link between folic acid supplementation during later pregnancy and epigenetic changes and identify a novel mechanism for regulation of ZFP57. This trial was registered 15 May 2013 at www.isrctn.com as ISRCTN19917787.

Objective: To investigate the effects of Aquilaria subintegra leaf aqueous extracts on the aphrodisiac properties including sexual behaviour, testosterone level, percentage of pregnancy, number of offspring and male to female ratio of offspring in ICR mice. Methods: In this experiment, each male cohabitated with one female in a polysulfone cage. 30 ICR male mice were divided into 6 groups that received normal saline (the control group), 50 mg/kg, 100 mg/kg, 200 mg/kg, 500 mg/kg, and 1 000 mg/kg body weight of Aquilaria subintegra leaf aqueous extracts orally for 21 days consecutively. Sexual behavior, percentage of pregnancy, number of offspring and male to female ratio of offspring in ICR mice were measured according to the established methods. Testosterone level was measured by using enzyme-linked immunosorbent assay. Results: Mice that received Aquilaria subintegra leaf aqueous extracts at 50 mg/kg body weight (day 0) had significantly higher mount frequency as compared to the control group; groups treated with 100, 500, 1 000 mg/kg body weight extracts produced a greater number of offsprings when compared to the control group. All aphrodisiac parameters were similar between the treatment groups and the control group, indicating that Aquilaria subintegra leaf aqueous extract did not significantly alter the aphrodisiac parameters. Conclusions: Aquilaria subintegra leaf aqueous extracts have no effect on the aphrodisiac properties, but could increase the breeding rate in mice.

Background and purpose: Ghrelin, a natural ligand of the growth hormone secretagogue receptor plays a major role in regulation of appetite, body fat mass, and energy balance in the body. The aim of this study was to evaluate the effects of maternal diabetes on circulatory ghrelin levels in rat newborns. Materials and methods: In this experimental study, female Wistar rats were allocated into diabetic (n=20) and control (n=10) groups and mated with males. After parturition, 16 offspring (8 males) were collected at both postnatal days (P), P7 and P14. The body weight, blood glucose and plasma ghrelin levels were measured. Data were analyzed applying two-way ANOVA using sex and group as the factors in SPSS V22. Results: At both P7 and P14, the body weight of newborns of diabetic mothers (18.49± 0.42g, 22.27± 0.43g respectively) were significantly lower (P

Background: This study explored the mechanisms underlying altered neurobehavioural development of female offspring born to mothers with polycystic ovary syndrome (PCOS). Methods: In total, 20 women with PCOS and 32 healthy women who underwent caesarean deliveries with a single female foetus were recruited. Infants were assessed with Dubowitz scoring. Swan71 cell line with stable FOS overexpression was used to verify the regulatory effects of FOS on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) expression. Learning and memory in female first-generation (F1) and second-generation (F2) offspring in a rat model of PCOS was tested using the Morris water maze at puberty and adulthood. Transcriptome analysis of pubertal hippocampi and hypothalami of female F1 offspring was conducted. Findings: Total score and behaviour subscales of Dubowitz scoring were significantly lower in female infants of women with PCOS. FOS and NGF protein levels were downregulated in placental villi of the PCOS group. FOS played a key role in BDNF inhibition and enhancing NGF in Swan71 cells. PCOS female F1 rats exhibited lower target crossing times during puberty when compared to controls. Transcriptome analysis revealed significant changes in hippocampal and hypothalamic neuronal pathways in female F1 rats at puberty. Interpretation: FOS regulation of neurotrophins in the placenta negatively affects neurobehavioural development of female offspring of PCOS mothers. Funding: This study was funded by the National Key R&D Program of China (2018YFC1004900 to F.Q. and F.W.) and the National Natural Science Foundation of China (81874480 to F.Q.; 81873837 to F.W.).

Background Maternal malnutrition is a critical factor in determining the risk of obesity and glucose intolerance in offspring. However, little is known about the effects of a maternal high-fat diet (HFD) on the β cell phenotype in offspring, which is a major factor in glucose homeostasis, especially during the early life of offspring. Methods Dams were randomly fed a HFD (60% kcal from fat) or a chow diet before pregnancy and during gestation and lactation. Glucose metabolism and the β cell phenotype were assessed in male offspring at weaning. Results Dams fed a HFD showed impaired glucose tolerance. A HFD predisposed the offspring to increased impairment of metabolic health, including obesity, glucose intolerance and insulin resistance, compared with offspring from chow diet-fed dams. Furthermore, increased islet sizes and islet densities were observed in male offspring from HFD-fed dams at weaning. There were increases in the insulin-positive area, β cell mass and β cell proliferation in male offspring from HFD-fed dams at weaning age. Next, we further determined whether a maternal HFD could affect β cell apoptosis in mouse offspring and found that there was no significant change in β cell apoptosis between the HFD and control groups. Conclusion Our study is novel in showing that a maternal HFD predisposes offspring to impaired glucose metabolism and has a profound effect on β cell mass and proliferation in offspring mice, which is observed in mice as early as at weaning age. However, further study to clarify the underlying mechanisms is warranted.

Abstract Background It is presumed that pharmacological and non-pharmacological treatment of prenatal common mental disorders can mitigate associated adverse effects in offspring, yet strong evidence for the prophylactic benefits of treatment is lacking. We therefore examined the effect of prenatal treatments for common mental disorders on offspring outcomes. Methods For this meta-analysis, articles published up to August 31, 2017, were obtained from PubMed, PsycInfo, Embase, and Cochrane databases. Included studies needed to be randomized controlled trials (RCTs) on the effect of treatment of prenatal common mental disorders comparing an intervention to a control condition, including offspring outcome(s). Random effects models were used to calculate Hedges’ g in the program Comprehensive Meta-Analysis© (version 3.0). Results Sixteen randomized controlled trials among 2778 pregnant women compared offspring outcomes between prenatal interventions and control groups. There were zero pharmacological, 13 psychological, and three other interventions (homeopathy, relaxation interventions, and short psycho-education). Birth weight (mean difference 42.88 g, g = 0.08, 95% CI −0.06 to 0.22, p = 0.27, n = 11), Apgar scores (g = 0.13, 95% CI −0.28 to 0.54, p = 0.53, n = 4), and gestational age (g = 0.03, 95% CI −0.06 to 0.54, p = 0.49, n = 10) were not significantly affected. Other offspring outcomes could not be meta-analyzed due to the inconsistent reporting of offspring outcomes and an insufficient number of studies. Conclusions Non-pharmacological interventions had no significant effect on birth outcomes, although this outcome should be considered with caution due to the risk of biases. No randomized controlled trial examined the effects of prenatal pharmacological treatments as compared to treatment as usual for common mental disorders on offspring outcomes. Present clinical guidelines may require more research evidence on offspring outcomes, including child development, in order to warrant the current recommendation to routinely screen and subsequently treat prenatal common mental disorders. Trial registration PROSPERO CRD42016047190

Background. The functions of the jejunum are diverse, but all of them to some extent ensure the implementation of the two leading processes in the body: hydrolysis of nutrients that have been taken and their absorption. Objective: to study, in normal conditions, the features of the age-related formation of structural and cytochemical indices of the jejunum of rats in postnatal ontogenesis. Material and methods. The experiment was performed on 35 rats of 15-, 45- and 90-day old age. A complex of histological, histochemical, electron microscopic methods was used with subsequent morphometric and statistical analysis. Results. It was established that the structural organization of the jejunum develops intensively from the 15th to the 45th day, which is probably due to the transition from dairy to definitive type of nutrition. Conclusions. The microvillous epithelium is already completely formed by the 15th day and has a high structural and cytochemical organization providing an intensive level of parietal digestion right after birth and absorption of the monomers that form.

Introduction : Maternal hypoxia induces an adverse uterine environment and may induce long-term effects in offspring. This study investigated whether maternal hypoxia increases hippocampal cell vulnerability and exacerbates neurological impairments in adult rat offspring following ischemia. Material and methods : Pregnant Sprague-Dawley rats were randomly assigned to no maternal hypoxia or maternal hypoxia treatment groups. Adult male rat offspring were subjected to middle cerebral artery occlusion (MCAO). There were four groups: maternal + sham (MH + Sham), sham (Sham), maternal hypoxia + MCAO (MH + MCAO), and MCAO only (MCAO). Neurological deficits were evaluated. Hippocampal cell damage was observed by hematoxylin and eosin (HE) staining. Cell apoptosis in the hippocampus was detected by TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining. Caspase-3, cytochrome c, Bax, and bcl-2 expression in the hippocampus was detected by Western blot. Results : More severe hippocampal cell damage was found in the MH + MCAO group than in the MCAO group. Additionally, neurological deficits, percentage of TUNEL positive cells, and expression of caspase-3, cytochrome c, and Bax in the hippocampus were significantly higher (p < 0.05), whereas bcl-2 expression was significantly lower (p < 0.05) in the MH + MCAO group compared to the MCAO group. Conclusions : These findings suggest that maternal hypoxia may exacerbate hippocampal cell apoptosis in rat offspring after MCAO via alterations in the expression of cytochrome c, caspase-3, Bax, and bcl-2, which ultimately affects ischemic stroke prognosis. To our knowledge, this is the first study demonstrating that maternal hypoxia increases hippocampal cell susceptibility to ischemia in adult rat offspring.

Outcomes of Zika virus (ZIKV) infection in pregnant women vary from the birth of asymptomatic offspring to abnormal development and severe brain lesions in fetuses and infants. There are concerns that offspring affected in utero and born without apparent symptoms may develop mental illnesses. Therefore, animal models are important to test interventions against in utero infection and health sequelae in symptomatic and likely more widespread asymptomatic offspring. To partially reproduce in utero infection in humans, we directly inoculated selected porcine conceptuses with ZIKV. Inoculation resulted in rapid trans-fetal infections, persistent infection in conceptuses, molecular pathology in fetal brains, fetal antibody and type I interferon responses. Offspring infected in utero showed ZIKV in their fetal membranes collected after birth. Some in utero affected piglets were small, depressed, had undersized brains, and showed seizures. Some piglets showed potentially increased activity. Our data suggest that porcine model of persistent in utero ZIKV infection has a strong potential for translational research and can be used to test therapeutic interventions in vivo.

Abstract Objective An excessive rise in blood lipids during pregnancy may promote metabolic dysfunction in adult progeny. We characterized how maternal phytosterol (PS) supplementation affected serum lipids and the expression of lipid-regulatory genes in the intestine and liver of newly-weaned apo-E deficient offspring from dams fed a chow diet supplemented with cholesterol (0.15%, CH) or cholesterol and PS (2%) (CH/PS) throughout pregnancy and lactation. Results Serum lipid concentrations and lipoprotein particle numbers were exacerbated in offspring from cholesterol-supplemented mothers but normalized to chow-fed levels in pups exposed to PS through the maternal diet during gestation and lactation. Compared with the CH pups, pups from PS-supplemented mothers demonstrated higher (p

ABSTRACT Background and Objectives: Hippocampus is the main structure involved in spatial learning and memory consolidation. Formation of spatial memory can be strongly influenced by medications, hormones and different substances. Due to importance of new pharmacotherapy on drug administration in pregnancy, the aim of this study was to investigate the effect of letrozole-therapy during pregnancy on memory and learning in offspring rats. Methods: In this study, 24 pregnant rats were divided into a control and three experimental groups (N=6). The subjects received low dose (0.25 mg/Kg), average dose (0.5 mg/Kg) and high dose (1 mg/Kg) of letrozole orally during 16-19 days of gestation. After maturating, learning and memory of the offspring were assessed by passive avoidance learning apparatus. Data were analyzed by SPSS 20 using one-way analysis of variance and the Tukeychr('39')s test. P-values less than 0.05 were considered statistically significant. Results: Weights of the offspring who received letrozole decreased significantly compared with the control. There was no significant difference in the step-through latency between the experimental groups. However, the step-through latency and time spent in the dark compartment decreased significantly in the experimental groups compared with control group (P

Background: Ovarian hyperstimulation syndrome (OHSS), a complication of ovarian stimulation, has various adverse effects on both pregnant women and their offspring. However, whether OHSS will affect intellectual ability in offspring is still unknown. Methods: We recruited 86 Chinese children born to OHSS women and 172 children conceived with non-OHSS In Vitro Fertilization (IVF) in this cohort study. Their intellectual ability was assessed according to the Revised Chinese Version of the Wechsler Intelligence Scale for Children (C-WISC). Verbal Intelligence Quotient (VIQ), Performance Intelligence Quotient (PIQ), and Full Intelligence Quotient (FIQ) were calculated. The investigation was registered in Chinese Clinical Trial Registry (ChiCTR-SOC-16009555). Findings: OHSS offspring scored less on C-WISC (mean (standard deviation [SD]): (VIQ = 92.7 (14.7), PIQ = 108.9 (13.1), FIQ = 100.6 (13.4)) compared with non-OHSS IVF offspring (VIQ = 100.1 (13.2), PIQ = 113.7 (10.8), FIQ = 107.4 (11.5)). The prevalence of low IQ (

Background: Excessive androgen exposure during pregnancy has been suggested to induce diabetic phenotypes in offspring in animal models. The aim of this study was to investigate whether pregestational maternal hyperandrogenism in human influenced the glucose metabolism in offspring via epigenetic memory from mother's oocyte to child's somatic cells. Methods: Of 1782 reproductive-aged women detected pregestational serum androgen, 1406 were pregnant between 2005 and 2010. Of 1198 women who delivered, 1116 eligible mothers (147 with hyperandrogenism and 969 normal) were recruited. 1216 children (156 children born to mothers with hyperandrogenism and 1060 born to normal mother) were followed up their glycometabolism in mean age of 5 years. Imprinting genes of oocyte from mothers and lymphocytes from children were examined. A pregestational hyperandrogenism rat model was also established. Findings: Children born to women with hyperandrogenism showed increased serum fasting glucose and insulin levels, and were more prone to prediabetes (adjusted RR: 3.98 (95%CI 1.16–13.58)). Oocytes from women with hyperandrogenism showed increased insulin-like growth factor 2 (IGF2) expression. Lymphocytes from their children also showed increased IGF2 expression and decreased IGF2 methylation. Treatment of human oocytes with dihydrotestosterone upregulated IGF2 and downregulated DNMT3a levels. In rat, pregestational hyperandrogenism induced diabetic phenotypes and impaired insulin secretion in offspring. In consistent with the findings in human, hyperandrogenism also increased Igf2 expression and decreased DNMT3a in rat oocytes. Importantly, the same altered methylation signatures of Igf2 were identified in the offspring pancreatic islets. Interpretation: Pregestational hyperandrogenism may predispose offspring to glucose metabolism disorder via epigenetic oocyte inheritance. Clinical trial registry no.: ChiCTR-OCC-14004537; www.chictr.org.

Objective(s): The link between a hyperglycemic intrauterine environment and the development of diabetes later in life has been observed in offspring exposed to gestational diabetes mellitus (GDM), but the underlying mechanisms for this phenomenon are still not clear. Reduced β-cells mass is a determinant in the development of diabetes (type 1 and type 2 diabetes). Some recent studies have provided evidence that the CDK4-pRB-E2F1 regulatory pathway is involved in β-cells proliferation. Therefore, we postulated that GDM exposure impacts the offspring’s β-cells by disruption in the CDK4-pRB-E2F1 pathway. Materials and Methods: Adult Wistar rats were randomly allocated in control and diabetic group. The experimental group received 40 mg/kg/body weight of streptozotocin (STZ) on day zero of gestation. After delivery, diabetic offspring of GDM mothers and control dams at the age of 15 week were randomly scarified and pancreases were harvested. Langerhans islets of diabetic and control groups were digested by collagenase digestion technique. After RNA extraction, we investigated the expressions of the kir 6.2 and CDK4-pRB-E2F1 pathway genes by quantitative real-time PCR. Results: GDM reduced the expression of CDK4-pRB-E2F1 pathway genes in Langerhans islets cells of offspring. CDK4, pRB and E2F1 pathway genes were downregulated in diabetic islets by 51%, 35% and 84%, respectively. Also, the expression of Kir 6.2 was significantly decreased in diabetic islets by 88%. Conclusion: We suggest that the effect of gestational diabetes on offspring’s β-cells may be primarily caused by the suppression of CDK4-pRB-E2F1 pathway.