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The use of cannabis during pregnancy has emerged as a mounting cause for concern due to its potential adverse consequences on both the mother and her offspring. This review will focus on the dangers associated with prenatal exposure to cannabis, particularly those related to neurodevelopment. It will also discuss the features of maternal and placental functioning that are likely to have long-term effects on the offspring's development. The most pertinent and up-to-date materials can be found through a literature search. The literature emphasizes the substantial hazards associated with prenatal exposure to cannabis. These include impairments in cognitive function and difficulties in behavior in this particular instance. Structural and functional alterations in the brain can be noticed in offspring. The use of cannabis has been associated with an increased likelihood of experiencing pregnancy-related complications, such as giving birth prematurely and having a baby with a low birth weight. Additionally, it has been connected to potential negative effects on mental and emotional well-being. Studies have shown that when a pregnant woman is exposed to cannabis, it can negatively impact the functioning of the placenta and the growth of the fetus. This might potentially contribute to the development of placental insufficiency and restricted growth in the womb. Longitudinal studies reveal that children who were exposed to cannabis in the womb experience additional long-term developmental challenges, such as decreased cognitive abilities, reduced academic performance, and behavioral issues. In order to address the problem of cannabis usage during pregnancy, it is essential to adopt a comprehensive and coordinated strategy. This method should integrate and synchronize public health policy, education, and research initiatives. By implementing these targeted strategies, it is possible to mitigate potential health and welfare concerns for both present and future generations. [ABSTRACT FROM AUTHOR]

Background/Objectives: The utility of shear wave elastography (SWE) as an adjunct to ultrasound biometry and Doppler velocimetry for the examination of placental dysfunction and suboptimal fetal growth is unclear. To date, limited data exist correlating the mechanical properties of placentae with fetal growth. This study aimed to investigate the relationship between placental shear wave velocity (SWV) and ultrasound estimated fetal weight (EFW), and to ascertain if placental SWV is a suitable proxy measure of placental function in the surveillance of small-for-gestational-age (SGA) pregnancies. Methods: This prospective, observational cohort study compared the difference in placental SWV between SGA and appropriate-for-gestational-age (AGA) pregnancies. There were 221 women with singleton pregnancies in the study cohort—136 (61.5%) AGA and 85 (38.5%) SGA. Fetal biometry, Doppler velocimetry, the deepest vertical pocket of amniotic fluid, and mean SWV were measured at 2–4-weekly intervals from recruitment to birth. Results: There was no difference in mean placental SWV in SGA pregnancies compared to AGA pregnancies, nor was there any relationship to EFW. Conclusions: Although other studies have shown some correlation between increased placental stiffness and SGA pregnancies, our investigation did not support this. The mechanical properties of placental tissue in SGA pregnancies do not result in placental SWVs that are apparently different from those of AGA controls. As this study did not differentiate between constitutionally or pathologically small fetuses, further studies in growth-restricted cohorts would be of benefit. [ABSTRACT FROM AUTHOR]

Objectives: T2*‐weighted magnetic resonance imaging (MRI) sequences have been identified as non‐invasive tools with which to study placental oxygenation in vivo. This study aimed to use these to investigate both static and dynamic responses to hyperoxia of the normal placenta across gestation. Methods: We conducted a single‐center prospective study including 52 uncomplicated pregnancies. Two T2*‐weighted sequences (T2* relaxometry) were performed, one before and one after maternal hyperoxia. The distribution of placental T2* values was modeled by fitting a gamma probability density function (T2* ~Γαβ), describing the structure of the histogram using the mean T2* value, the shape parameter (α) and the rate (β). A dynamic acquisition (blood‐oxygen‐level‐dependent (BOLD) MRI) was also performed before and during maternal oxygen supply, until placental oxygen saturation had been achieved. The signal change over time was modeled using a sigmoid function, to determine the intensity of enhancement (ΔBOLD (% with respect to baseline)), a temporal variation coefficient (λ (min–1), controlling the slope of the curve) and the maximum steepness (Vmax (% of placental enhancement/min)). Results: The histogram analysis of the T2* values in normoxia showed a whole‐placenta variation, with a decreasing linear trend in the mean T2* value (Pearson's correlation coefficient (R) = −0.83 (95% CI, −0.9 to −0.71), P < 0.001), along with an increasingly peaked and narrower distribution of T2* values with advancing gestation. After maternal hyperoxia, the mean T2* ratios (mean T2*hyperoxia/mean T2*baseline) were positively correlated with gestational age, while the other histogram parameters remained stable, suggesting a translation of the histogram towards higher values with a similar appearance after maternal hyperoxia. ΔBOLD showed a non‐linear increase across gestation. Conversely, λ showed an inverted trend across gestation, with a weaker correlation (R = −0.33 (95% CI, −0.58 to −0.02), P = 0.04, R2 = 0.1). As a combination of ΔBOLD and λ, the changes in Vmax throughout gestation were influenced mainly by the changes in ΔBOLD and showed a positive non‐linear correlation with gestational age. Conclusions: Our results suggest that the decrease in the T2* placental signal as gestation progresses does not reflect placental dysfunction. The BOLD dynamic signal change is representative of a free‐diffusion model of oxygenation and highlights the increasing differences in oxygen saturation between mother and fetus as gestation progresses (ΔBOLD) and in the placental permeability to oxygen (λ). © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Intrauterine growth restriction (IUGR) severely impairs fetal development and offspring health. Odd-chain fatty acid (OCFA) possess beneficial biological activities in regulating insulin resistance, inflammation and oxidative stress. However, the effects of OCFA on improving IUGR through regulating placental function and maternal health remain unclear. Herein, maternal OCFA-rich algal oil supplementation improved variable coefficient of fetal weight and fetal oxidative stress in low protein diet (LPD)-induced IUGR mice model. OCFA-rich algal oil also improved placental dysfunction, placental fatty acid metabolism disorder, maternal insulin resistance, oxidative stress and intestinal injury, suggesting an improved maternal health. OCFA-rich algal oil reshaped the intestinal microbiome of dams, decreasing unclassified Bacteroidales and Parvibacter, and increasing Weissella, which positively impacted insulin resistance and intestinal injury. Overall, OCFA-rich algal oil supplementation during pregnancy ameliorated oxidative stress, insulin resistance and intestinal injury in LPD-induced IUGR pregnant mice, improved placental functions and litter characteristics, and further enhanced fetal antioxidant capacity.

Understanding the mechanisms by which environmental factors impact reproductive health is crucial for informing public health interventions and policy decisions. By elucidating the pathways through which environmental stressors exert their effects, we can develop targeted strategies to mitigate risks and promote reproductive well-being. In this lecture, we will delve into the latest research findings and emerging trends in the field of environmental reproductive health. By exploring the intricate interplay between environmental exposures and reproductive outcomes, we aim to broaden our understanding of this complex relationship and its implications for human health. Through collaborative efforts across disciplines, we can work towards safeguarding reproductive health for current and future generations.

The use of cannabis during pregnancy has emerged as a mounting cause for concern due to its potential adverse consequences on both the mother and her offspring. This review will focus on the dangers associated with prenatal exposure to cannabis, particularly those related to neurodevelopment. It will also discuss the features of maternal and placental functioning that are likely to have long-term effects on the offspring’s development. The most pertinent and up-to-date materials can be found through a literature search. The literature emphasizes the substantial hazards associated with prenatal exposure to cannabis. These include impairments in cognitive function and difficulties in behavior in this particular instance. Structural and functional alterations in the brain can be noticed in offspring. The use of cannabis has been associated with an increased likelihood of experiencing pregnancy-related complications, such as giving birth prematurely and having a baby with a low birth weight. Additionally, it has been connected to potential negative effects on mental and emotional well-being. Studies have shown that when a pregnant woman is exposed to cannabis, it can negatively impact the functioning of the placenta and the growth of the fetus. This might potentially contribute to the development of placental insufficiency and restricted growth in the womb. Longitudinal studies reveal that children who were exposed to cannabis in the womb experience additional long-term developmental challenges, such as decreased cognitive abilities, reduced academic performance, and behavioral issues. In order to address the problem of cannabis usage during pregnancy, it is essential to adopt a comprehensive and coordinated strategy. This method should integrate and synchronize public health policy, education, and research initiatives. By implementing these targeted strategies, it is possible to mitigate potential health and welfare concerns for both present and future generations.

Trophoblast cell syncytialization is essential for placental and fetal development. Abnormal trophoblast cell fusion leads to pregnancy pathologies, such as preeclampsia (PE), intrauterine growth restriction (IUGR), and miscarriage. 27-hydroxycholesterol (27-OHC) is the most abundant oxysterol in human peripheral blood synthesized by sterol 27-hydroxylase (CYP27A1) and is considered a critical mediator between hypercholesterolemia and a variety of related disorders. Gestational hypercholesterolemia was associated with spontaneous preterm delivery and low birth weight (LBW) in term infants, yet the mechanism is unclear. In this study, two trophoblast cell models and CD-1 mice were used to evaluate the effects of 27-OHC on trophoblast fusion during placenta development. Two different kinds of trophoblast cells received a dosage of 2.5, 5, or 10 uM 27-OHC. Three groups of pregnant mice were randomly assigned: control, full treatment (E0.5-E17.5), or late treatment (E13.5-E17.5). All mice received daily intraperitoneal injections of saline (control group) and 27-OHC (treatment group; 5.5 mg/kg). In vitro experiments, we found that 27-OHC inhibited trophoblast cell fusion in primary human trophoblasts (PHT) and forskolin (FSK)-induced BeWo cells. 27-OHC up-regulated the expression of the PI3K/AKT/mTOR signaling pathway-related proteins. Moreover, the PI3K inhibitor LY294002 rescued the inhibitory effect of 27-OHC. Inhibition of trophoblast cell fusion by 27-OHC was also observed in CD-1 mice. Furthermore, fetal weight and placental efficiency decreased and fetal blood vessel development was inhibited in pregnant mice treated with 27-OHC. This study was the first to prove that 27-OHC inhibits trophoblast cell fusion by Activating PI3K/AKT/mTOR signaling pathway. This study reveals a novel mechanism by which dyslipidemia during pregnancy results in adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Duplicated genes or paralogs play important roles in the adaptive function of eukaryotic genomes. Animal studies have shown evidence for the functional role of paralogs in pregnancy, but our knowledge about the role of paralogs in the fetoplacental regulation remains limited. In particular, if fetoplacental metabolic regulation is modulated by differential expression of paralogs remains unexamined. In this study, gene expression profiles of day-15 placenta and fetal brain were compared to identify families or groups of paralogous genes expressed in the placenta and brain of male versus female fetuses in mice. A Bayesian modeling was applied to infer directional relationship of transcriptional variation of the paralogs relative to the phylogenetic variation of the genes in each family. Gas chromatography-mass spectrometry (GC-MS) was used to perform untargeted metabolomics analysis of day-15 placenta and fetal brain of both sexes. We identified paralog groups that were expressed in a sex and/or tissue biased manner between the placenta and fetal brain. Bayesian modeling showed evidence for directional relationship between expression and phylogeny of specific paralogs. These relationships were sex specific. GC-MS analysis identified metabolites that were expressed in a sex-bias manner between the placenta and fetal brain. By performing integrative analysis of the metabolomics and gene expression data, we showed that specific groups of metabolites and paralogous genes were expressed in a coordinated manner between the placenta and fetal brain. The findings of this study collectively suggest that paralogs play an influential role in the regulation of the brain-placental axis in mice. • Differential expression of paralogs between the placenta and fetal brain. • Sex-bias metabolic changes between the placenta and fetal brain. • Fetal sex influences paralog expression in the placenta and brain. • Evidence for directional selection of paralog expression. • Association of paralogs with metabolism of the placenta and fetal brain. [ABSTRACT FROM AUTHOR]

The placenta plays a critical role in fetal development. It serves as a multi-functional organ that protects and nurtures the fetus during pregnancy. However, despite its importance, the intricacies of placental structure and function in normal and diseased states have remained largely unexplored. Thus, in 2014, the National Institute of Child Health and Human Development launched the Human Placenta Project (HPP). As of May 2023, the HPP has awarded over $101 million in research funds, resulting in 41 funded studies and 459 publications. We conducted a comprehensive review of these studies and publications to identify areas of funded research, advances in those areas, limitations of current research, and continued areas of need. This paper will specifically review the funded studies by the HPP, followed by an in-depth discussion on advances and gaps within placental-focused imaging. We highlight the progress within magnetic reasonance imaging and ultrasound, including development of tools for the assessment of placental function and structure. • The HPP predominantly funded studies on imaging and specimen collection with omic analysis. • Magnetic resonance imaging (MRI) studies received the greatest portion of funds. • Techniques included arterial spin labeled and blood oxygen dependent level MRI. • Advances shifted towards human data and automation of imaging processes. • Gaps include standardized ascertainment and analyses, full automation, and diseased population data. [ABSTRACT FROM AUTHOR]

Synopsis: We introduce a new microflow imaging technique, which can show the blood perfusion and morphological structure of placental villi. [ABSTRACT FROM AUTHOR]

Mitochondrial fatty acid oxidation (FAO) is lower in placentas with pre-eclampsia. The aim of our study was to compare the placental mRNA expression of FAO enzymes in healthy pregnancies vs. different subgroups of pre-eclampsia according to the severity, time of onset, and the presence of intrauterine growth restriction (IUGR). By using real-time qPCR, we measured the mRNA levels of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), medium-chain acyl-CoA dehydrogenase (MCAD), and carnitine palmitoyltransferases 1A and 2 (CPT1A, CPT2) on the maternal side (anchoring villi in the basal decidua) and on the fetal side (chorionic plate) of the placenta (n = 56). When compared to the controls, LCHAD, MCAD, and CPT2 mRNA had decreased in all pre-eclampsia subgroups globally and on the fetal side. On the maternal side, LCHAD mRNA was also lower in all pre-eclampsia subgroups; however, MCAD and CPT2 mRNA were only reduced in severe and early-onset disease, as well as CPT2 in IUGR (p < 0.05). There were no differences in CPT1A mRNA expression. We conclude that the FAO enzymes mRNA in the placenta was lower in pre-eclampsia, with higher reductions observed in severe, early-onset, and IUGR cases and more striking reductions on the fetal side. [ABSTRACT FROM AUTHOR]

Objectives: Evidence regarding placental function in pregnancies complicated by confined placental mosaicism (CPM) is conflicting. We aimed to compare placental function between CPM and non‐CPM pregnancies prenatally and at birth. A secondary objective was to evaluate the relationship between placental function and chromosomal subtype of CPM. Methods: This was a retrospective study of pregnancies with CPM and control pregnancies delivered at a tertiary hospital in Denmark between 2014 and 2017. Placental volume and placental transverse relaxation time (T2*) were estimated on magnetic resonance imaging (MRI), fetal weight and uterine artery pulsatility index (UtA‐PI) were estimated on ultrasound and fetoplacental ratio was assessed on MRI and at birth. These estimates of placental function were adjusted for gestational age and compared between groups using the Wilcoxon rank‐sum test. Within the group of CPM pregnancies, measures of placental function were compared between those at high risk (chromosome numbers 2, 3, 7, 13 and 16) and those at low risk (chromosome numbers 5, 18 and 45X). Results: A total of 90 pregnancies were included, of which 12 had CPM and 78 were controls. MRI and ultrasound examinations were performed at a median gestational age of 32.6 weeks (interquartile range, 24.7–35.3 weeks). On MRI assessment, CPM placentae were characterized by a lower placental T2* Z‐score (P = 0.004), a lower fetoplacental ratio (P = 0.03) and a higher UtA‐PI Z‐score (P = 0.03), compared with non‐CPM placentae. At birth, the fetoplacental ratio was significantly lower (P = 0.02) and placental weight Z‐score was higher (P = 0.01) in CPM pregnancies compared with non‐CPM pregnancies. High‐risk CPM pregnancies showed a reduced placental T2* Z‐score (P = 0.003), lower birth‐weight Z‐score (P = 0.041), earlier gestational age at delivery (P = 0.019) and higher UtA‐PI Z‐score (P = 0.028) compared with low‐risk CPM pregnancies. Low‐risk CPM pregnancies did not differ in any of these parameters from non‐CPM pregnancies. Conclusions: CPM pregnancies are characterized by an enlarged and dysfunctional placenta. Placental function was highly related to the chromosomal type of CPM; placental dysfunction was seen predominantly in high‐risk CPM pregnancies in which chromosomes 2, 3, 7, 13 or 16 were involved. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Based on epidemiological observations Barker et al. put forward the hypothesis/concept that an adverse intrauterine environment (involving an insufficient nutrient supply, chronic hypoxia, stress, and toxic substances) is an important risk factor for the development of chronic diseases later in life. The fetus responds to the unfavorable environment with adaptive reactions, which ensure survival in the short run, but at the expense of initiating pathological processes leading to adult diseases. In this review, the major mechanisms (including telomere dysfunction, epigenetic modifications, and cardiovascular–renal–endocrine–metabolic reactions) will be outlined, with a particular emphasis on the role of oxidative stress in the fetal origin of adult diseases. [ABSTRACT FROM AUTHOR]

Objective: Birth weight, fetal growth and placental function influence cognitive development. The gradient of these associations is understudied, especially among those with a birth weight considered appropriate‐for‐gestational age. The aim of this study was to evaluate the associations between birth‐weight centile and intellectual development in term/near‐term infants across the entire birth‐weight spectrum, in order to provide a basis for better understanding of the long‐term implications of fetal growth restriction and reduced placental function. Methods: This was a population‐based cohort study of 266 440 liveborn singletons from uncomplicated pregnancies, delivered between 36 and 42 weeks of gestation. Perinatal data were obtained from the Dutch Perinatal Registry over the period 2003–2008 and educational data for children aged approximately 12 years were obtained from Statistics Netherlands over the period 2016–2019. Regression analyses were conducted to assess the association of birth‐weight centile with school performance. The primary outcomes were mean school performance score, on a scale of 501–550, and proportion of children who reached higher secondary school level. Results: Mean school performance score increased gradually with increasing birth‐weight centile, from 533.6 in the 1st–5th birth‐weight‐centile group to 536.8 in the 81st–85th birth‐weight‐centile group. Likewise, the proportion of children at higher secondary school level increased with birth‐weight centile, from 43% to 57%. Compared with the 81st–85th birth‐weight‐centile group, mean school performance score and proportion of children at higher secondary school level were significantly lower in all birth‐weight‐centile groups below the 80th centile, after adjusting for confounding factors. Conclusions: Birth‐weight centile is associated positively with school performance at 12 years of age across the entire birth‐weight spectrum, well beyond the conventional and arbitrary cut‐offs for suspected fetal growth restriction. This underlines the importance of developing better tools to diagnose fetal growth restriction and reduced placental function, and to identify those at risk for associated short‐ and long‐term consequences. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background:Empirical use of Hydroxychloroquine (HCQ) in patients with positive antinuclear antibody spectrum (ANAs) test result is controversial regarding its impact on improving perinatal outcomes. This study aimed to investigate the effect of HCQ on adverse pregnancy outcomes associated with placental dysfunction in ANAs-positive patients.Methods:The study included pregnant women with positive ANAs test result from 2016 to 2020 in our center, and divided into a weakly positive and a positive group in just ANA positive patients among them. Univariate and multivariate analyses were conducted to determine the effect of HCQ on pregnancy outcomes in each subgroup. Stratified and interactive analyses were performed to assess the value of HCQ in improving pregnancy outcomes.Results:(i) A total of 261 cases were included, accounting for 30.60% of pregnancy complicated with autoimmune abnormalities, and 65.12% of them used HCQ during pregnancy. (ii) The application of HCQ significantly reduced the incidence of early-onset preeclampsia (1.18% vs. 12.09%, p = 0.040) and small-for-gestational-age infants (10.06% vs. 25.84%, p = 0.003) in the ANAs-positive population, increased birth weight (3075.87 ± 603.91 g vs. 2847.53 ± 773.73 g, p = 0.025), and prolonged gestation (38.43 ± 2.31 vs. 36.34 ± 5.45 weeks, p

Simple Summary: Despite the relevance of biometrical and blood flow assessments for studying fetoplacental physiology during pregnancy, there is no detailed description of any animal model, which is needed to extrapolate results to human pregnancy. Here, we examined biometry and intrauterine blood flow in pregnant guinea pigs from the second trimester until term. We show that fetal and placental biometry, as well as changes in the main vascular beds across pregnancy, compared qualitatively to data from humans. These findings emphasize that the guinea pig is a reliable model to study fetal development and placental function with translational significance for human pregnancy. Background: Biometrical and blood flow examinations are fundamental for assessing fetoplacental development during pregnancy. Guinea pigs have been proposed as a good model to study fetal development and related gestational complications; however, longitudinal growth and blood flow changes in utero have not been properly described. This study aimed to describe fetal and placental growth and blood flow of the main intrauterine vascular beds across normal guinea pig pregnancy and to discuss the relevance of this data for human pregnancy. Methods: Pregnant guinea pigs were studied from day 25 of pregnancy until term (day ~70) by ultrasound and Doppler assessment. The results were compared to human data from the literature. Results: Measurements of biparietal diameter (BPD), cranial circumference (CC), abdominal circumference, and placental biometry, as well as pulsatility index determination of umbilical artery, middle cerebral artery (MCA), and cerebroplacental ratio (CPR), were feasible to determine across pregnancy, and they could be adjusted to linear or nonlinear functions. In addition, several of these parameters showed a high correlation coefficient and could be used to assess gestational age in guinea pigs. We further compared these data to ultrasound variables from human pregnancy with high similarities. Conclusions: BPD and CC are the most reliable measurements to assess fetal growth in guinea pigs. Furthermore, this is the first report in which the MCA pulsatility index and CPR are described across guinea pig gestation. The guinea pig is a valuable model to assess fetal growth and blood flow distribution, variables that are comparable with human pregnancy. [ABSTRACT FROM AUTHOR]

COVID-19 is an ongoing pandemic and has been extensively studied. However, the effects of COVID-19 during pregnancy, particularly on placental function, have not been verified. In this study, we used blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) to evaluate whether COVID-19 incidence during pregnancy has any lasting effects with respect to placental oxygenation. This is a case-control study, in which eight cases of singleton pregnancies before 30 weeks gestation with COVID-19 mothers were included. Placental oxygenation was evaluated using BOLD-MRI after 32 weeks of gestation. BOLD-MRI was consecutively performed under normoxia (21% O2), hyperoxia (100% O2), and normoxia for 4 min each. Individual placental time–activity curves were evaluated to calculate the peak score (peakΔR2*) and the time from the start of maternal oxygen administration to the time of peakΔR2* (time to peakΔR2*). Eighteen COVID-19-free normal pregnancies from a previous study were used as the control group. No significant differences were found between the two groups regarding maternal background, number of days of delivery, birth weight, and placental weight. The parameter peakΔR2* was significantly decreased in the COVID-19 group (8 ± 3 vs. 5 ± 1, p <.001); however, there was no significant difference in time to peakΔR2* (458 ± 74 s vs. 471 ± 33 s, p =.644). In this study, BOLD-MRI was used to evaluate placental oxygenation during pregnancy in COVID-19-affected patients. COVID-19 during pregnancy decreased placental oxygenation even post-illness, but had no effect on fetal growth; further investigation of the possible effects of COVID-19 on the fetus and mother is warranted. [ABSTRACT FROM AUTHOR]

Intrauterine growth restriction (IUGR) severely impairs fetal development and offspring health. Odd-chain fatty acid (OCFA) possess beneficial biological activities in regulating insulin resistance, inflammation and oxidative stress. However, the effects of OCFA on improving IUGR through regulating placental function and maternal health remain unclear. Herein, maternal OCFA-rich algal oil supplementation improved variable coefficient of fetal weight and fetal oxidative stress in low protein diet (LPD)-induced IUGR mice model. OCFA-rich algal oil also improved placental dysfunction, placental fatty acid metabolism disorder, maternal insulin resistance, oxidative stress and intestinal injury, suggesting an improved maternal health. OCFA-rich algal oil reshaped the intestinal microbiome of dams, decreasing unclassified Bacteroidales and Parvibacter , and increasing Weissella , which positively impacted insulin resistance and intestinal injury. Overall, OCFA-rich algal oil supplementation during pregnancy ameliorated oxidative stress, insulin resistance and intestinal injury in LPD-induced IUGR pregnant mice, improved placental functions and litter characteristics, and further enhanced fetal antioxidant capacity. [Display omitted] • OCFA supplemented low protein-fed dams improves antioxidant capacity. • OCFA alleviates placental dysfunction and fetal intrauterine growth restriction. • OCFA supplemented low protein-fed dams improves insulin resistance. • OCFA supplemented low protein-fed dams improves intestinal barrier function. [ABSTRACT FROM AUTHOR]

Aim Noninvasive blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) has recently been used to evaluate placental oxygenation. However, this method still has unresolved problems, such as long testing times and lack of normal values set. In the present study, we used a shorter protocol in BOLD-MRI and established normal values for placental oxygenation in late pregnancy. Methods We recruited 18 healthy singleton pregnant women (>32 weeks of gestation) who had a normal body size before pregnancy and a normal course of pregnancy. They underwent BOLD-MRI with three consecutive 4-min periods of different oxygenation: normoxia (21% O2), hyperoxia (10 L O2/min), and then normoxia. Placental time–activity curves were presented as signal intensity change relative to baseline (ΔR2*). The time from starting maternal oxygen administration to peak ΔR2*. To assess the relationship between peak ΔR2* values and placenta-related parameters and fetal development, the correlation between peak ΔR2*, placental weight, and neonatal birth weight was evaluated using Spearman’s rank correlation test. Results In all cases, the BOLD signal was elevated by maternal oxygen administration, with the peak resolving within 4 min after the end of oxygen administration. Peak ΔR2* and time to peak ΔR2* during oxygenation were 7.99 ± 2.58, and 458.1 ± 73.9 s, respectively. There was a significant correlation between peak ΔR2* and neonatal birth weight (percentile) (r = 0.537, p = .022), and between placental weight and neonatal birth weight (r = 0.769, p < .01). Conclusions In all cases, the BOLD signal increased with maternal hyperoxia using this protocol. So, 4 min observation following maternal oxygen administration is sufficient for peak ΔR2* evaluation. These reference values set in this study may be one of the indicators of BOLD signal changes in normal pregnancies after 32 weeks of gestation. [ABSTRACT FROM AUTHOR]

Triadimefon is a fungicide that is broadly used to treat fungal diseases of plants. It causes developmental toxicity in the animal model. Whether triadimefon disrupts the placental function and the underlying mechanism remains unclear. Thirty-six female pregnant Sprague-Dawley rats were randomly assigned into four groups and were orally administered via gavage of triadimefon (0, 25, 50, and 100 mg/kg/day) for 10 days from gestational day (GD) 12–21. Triadimefon disrupted the structure of the placenta, leading to hypertrophy, abnormal hemodynamics, including fibrin exudation, edema, hemorrhage, infarction, and inflammation. RNA-seq analysis showed that triadimefon down-regulated the expression of developmental and metabolic genes, while up-regulating the immune/inflammatory genes. The qPCR showed that triadimefon markedly down-regulated the expression of Cpt1c , Scd2 , Ldlr , Dvl1 , Flt4 , and Vwf and their proteins, while up-regulating the expression of Cyp1a1 , Star , Ccl5, and Cx3cr1 and their proteins at 25–100 mg/kg. Western blot showed that triadimefon reduced the level of STAT3 at doses of 50 and 100 mg/kg and the phosphorylation of AMPK at 100 mg/kg. In conclusion, triadimefon severely damages the structure and function of the placenta, leading to placental hypertrophy, local blood circulation disorders, and inflammation and this may be associated with its down-regulation of genes related to metabolism and nutrient transport and the up-regulation of inflammatory genes via STAT3 and AMPK signals. [Display omitted] • Triadimefon reduces placental efficiency after gestational exposure. • Triadimefon increases placental thickness. • Triadimefon down-regulates the expression of nutrient transporter genes. • Triadimefon up-regulates the expression of inflammatory genes. • Triadimefon reduces AMPK phosphorylation and STAT3. [ABSTRACT FROM AUTHOR]

Introduction: Placental dysfunction is one of the most common causes of Intrauterine Fetal Demise (IUFD). Due to its characteristics, the placenta may be the target of molecular research aimed to investigate potential causes of IUFD. In the literature, there are no studies on human placentas that have investigated possible associations between somatic mutations and the occurrence of IUFD. The aim of this study was to identify the presence of gene mutations in placental tissues in a series of cases of IUFD and to evaluate potential correlations with placental microscopic findings.Materials and Methods: Thirty-seven samples of formalin-fixed and paraffin-embedded placental tissues were retrospectively selected from pregnancies ending in IUFD between 23rd to 40th week. Six control placentas of physiological pregnancies were included as controls. After sampling, made according to standardized protocol and conventional histopathological examination, placental tissues were subjected to DNA extraction and sequencing by means of Next Generation Sequencing with a 56-gene panel.Results: The most frequent mutation observed in 32/37 IUFD cases (86.5%) and absent in any of the 6 control placentas was in c-KIT gene, which is implicated in placental tissue differentiation. However, no significant correlation was found between the presence of individual gene mutations and placental histopatological findings.Discussion: As the present study found an elevated frequency of c-KIT mutation in IUFD, it further supports the hypothesis that c-KIT is involved in abnormal tissue differentiation leading to altered placental vascularization and function. [ABSTRACT FROM AUTHOR]

The prevalence of maternal obesity is increasing at an alarming rate, and is providing a major challenge for obstetric practice. Adverse effects on maternal and fetal health are mediated by complex interactions between metabolic, inflammatory, and oxidative stress signaling in the placenta. Endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) are common downstream pathways of cell stress, and there is evidence that this conserved homeostatic response may be a key mediator in the pathogenesis of placental dysfunction. We summarize the current literature on the placental cellular and molecular changes that occur in obese women. A special focus is cast onto placental ER stress in obese pregnancy, which may provide a novel link for future investigation. During maternal obesity, placental lipid accumulation, glycosylation end-products, and a shift in macrophage population contribute to chronic low-grade placental 'meta-inflammation'. Recent bioinformatic advances have highlighted mechanisms of placental lipid accumulation during maternal obesity, including fatty acid transporter expression, lipoprotein lipase activity, and alterations to mitochondrial metabolism. Inflammation and metabolic dysfunction increase placental oxidative and endoplasmic reticulum (ER) stress, and downstream activation of the placental unfolded protein response (UPR), all of which have been linked to complications of pregnancy, including fetal growth restriction, preeclampsia, and gestational diabetes. Human umbilical vein endothelial cells isolated from mothers with a high body mass index show evidence of ER stress, which can be recapitulated using high levels of glucose, palmitate, or acidosis in the culture medium. Recent evidence suggests that ER stress and UPR activation mediate adverse placental effects through alterations of nitric oxide metabolism and a shift in angiogenic balance. [ABSTRACT FROM AUTHOR]

Introduction: Maternal hyperthermia (i.e. heat stress) can adversely affect placental development and function, with severity varying based on pregnancy stage. During the last half of pregnancy, cow uterine blood flow increases 4.5-fold, and decreased maternal blood circulation can reduce placental diffusion capacity, impacting fetal growth., Material and Methods: Milk removal was discontinued (i.e. dried off) in multiparous pregnant Holstein cows 54 ± 5 days before expected calving and assigned to cooling (CLD) or heat stress (HT) treatments. Oxygen measurements were taken within ±3 h after birth (n = 7 per group) using the Rad-G Pulse Oximeter. RNA sequencing of cotyledonary tissue examined pathways and genes related to gas and oxygen transport., Results: Heifers exposed to late gestation in utero hypoxia (HT) had significantly lower oxygen saturation at birth compared with those from dams with normal (CLD) oxygen levels (83.4 % vs. 90.7 %, p = 0.03). The peripheral index of oxygen diffusion was also lower in HT-exposed heifers (2.04 % vs. 4.84 %, p = 0.01). Gene enrichment analysis of cotyledonary tissue revealed affected pathways, including response to hypoxia, oxygen transport, and VEGF signaling. Late gestation HT potentially influenced blood circulation and nitric oxide biosynthesis pathways, with various genes showing upregulation and downregulation., Discussion: The placenta is vital for fetal development, and late gestation hyperthermia can significantly affect its function, reducing fetal oxygen delivery and altering genes regulating placental gas and oxygen transport. These disruptions may result in fetal hypoxemia and growth restriction., Competing Interests: Declaration of competing interest None of the authors have any conflict of interest for the manuscript., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Placental function is vital to the fetal growth of sows, and resveratrol (RES) can protect cells against oxidative stress, which is one of the major factors impairing placental function. This study aimed to investigate the effect of dietary resveratrol (RES) on placental function and reproductive performance during late pregnancy in a sow model from the aspects of oxidative stress, insulin resistance, and gut microbiota. A total of 26 hybrid pregnant sows (Landrace × Yorkshire) with similar parity were randomly allocated into two groups (n = 13) and fed with a basal diet or a diet containing 200 mg/kg of resveratrol from day 85 of gestation until parturition. The dietary supplementation of RES increased the litter weight at parturition by 12.53% (p = 0.145), with ameliorated insulin resistance (HOMA-IR), increased triglyceride (TG) levels, and decreased interleukin (IL)-1β and IL-6 levels in serum (p < 0.05). Moreover, resveratrol increased the placental vascular density (p < 0.05) with the enhanced expression of nutrient transporter genes (SLC2A1 and SLC2A3) and antioxidant genes, such as superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) but declined the expression of inflammatory genes, such as IL-1β and IL-6 (p < 0.05). The characterization of the fecal microbiota revealed that resveratrol decreased the relative abundance of the Christensensllaceae R-7 group and Ruminococcaceae UCG-008 (p < 0.05), which had a positive linear correlation with the expression of IL-1β and IL-6 (p < 0.05), but had a negative linear correlation with the expression of SOD2, HO-1, SLC2A1, and SCL2A3 genes (p < 0.05). These data demonstrated that dietary supplementation with resveratrol can improve placental function with ameliorated insulin resistance, oxidative stress, and inflammation potentially by regulating Ruminococcaceae UCG-008 and the Christensensllaceae R-7 group in sows.

SARS-CoV-2 has infected more than 16 million people worldwide. Related complications and death from COVID-19 disease and their underlying pathophysiology are intensely investigated. Pregnant women are among the affected. Although the severity of disease in pregnancy does not appear to be increased, the effects of infection on pregnancy should not escape careful examination. The currently known receptor for the virus, ACE2, regulates the renin-angiotensin system and is increased during pregnancy. Virus-receptor interactions may have significant effects on placental function, fetal development, and maternal immunity. The manifestation of cardiovascular complications of infection produces the hypothesis that a significant effect of the virus may be its influence on the maternal vascular system. Interference with the vascular adaptations to pregnancy and the post-partum may have implications for concurrent and future pregnancies as well as for long-term cardiovascular health. We should not miss the opportunity to learn from this virus about the physiology of pregnancy. [ABSTRACT FROM AUTHOR]

Based on epidemiological observations Barker et al. put forward the hypothesis/concept that an adverse intrauterine environment (involving an insufficient nutrient supply, chronic hypoxia, stress, and toxic substances) is an important risk factor for the development of chronic diseases later in life. The fetus responds to the unfavorable environment with adaptive reactions, which ensure survival in the short run, but at the expense of initiating pathological processes leading to adult diseases. In this review, the major mechanisms (including telomere dysfunction, epigenetic modifications, and cardiovascular–renal–endocrine–metabolic reactions) will be outlined, with a particular emphasis on the role of oxidative stress in the fetal origin of adult diseases.

Background/Aim. The placenta is essential in pregnancy, facilitating nutrient and gas exchange between mother and fetus. However, the regulatory proteins involved in this process are not fully understood across gestation. This study aimed to identify the top 20 differentially expressed genes (DEGs) in the placenta across different pregnancy stages to elucidate the molecular mechanisms at play. Methods. Differential gene expression analysis was performed on the placental samples from the first, second, and third trimesters using microarray data from Gene Expression Omnibus and Array Express. Analysis was conducted in RStudio using the R programming language. DEGs were identified using a significance score (π-value) based on the method developed by Xiao Y et al. (2014), which combines fold change and p-value. Volcano plots were created to visualize DEGs, and the top 20 were analyzed for functional enrichment using STRING and EnrichR databases, including Gene Ontology and KEGG pathways. Results. In the transition from the first to the second trimester, significant DEGs included genes involved in steroid metabolism such as HSD11B1, HSD3B2, and HSD17B2. These genes are critical in the biosynthesis and metabolism of steroid hormones, essential for sustaining pregnancy and supporting fetal development. Enrichment analysis showed these genes were significantly associated with steroid biosynthesis and steroidogenesis pathways. For the transition from the second to the third trimester, different sets of genes were highlighted, particularly those related to endocrine regulation and pregnancy-specific functions. Key genes included CRH, INHBA, REN, and members of the pregnancy-specific glycoprotein (PSG) family. These genes are involved in hormone regulation, reproductive processes, and maintaining maternal-fetal homeostasis, with significant associations with pathways related to endocrine processes, reproductive health, and vascular function. For example, the involvement of CRH and REN in endocrine regulation suggests their role in modulating maternal and fetal physiology during the later stages of pregnancy. Also, the genes associated with vascular and hemostatic functions were identified, indicating the importance of maintaining proper blood flow and preventing bleeding complications as pregnancy progresses. Notable genes included SDC1 and HBE1, which are crucial for vascular integrity and oxygen transport. Volcano plots illustrated these shifts in gene expression, with the top 20 genes identified by π-value prominently displayed. Conclusions. This study provides an analysis of gene expression changes in the placenta throughout pregnancy, identifying key genes and pathways that regulate placental function and impact fetal development. These findings enhance the understanding of placental biology and may highlight potential targets for ensuring optimal fetal development. [ABSTRACT FROM AUTHOR]

Antiangiogenic factors are currently used for the prediction of preeclampsia. The present study aimed to evaluate the relationship between antiangiogenic factors and lipid and carbohydrate metabolism in maternal plasma and placenta. We analyzed 56 pregnant women, 30 healthy and 26 with preeclampsia (including early and late onset). We compared antiangiogenic factors soluble Fms-like Tyrosine Kinase-1 (sfLt-1), placental growth factor (PlGF), and soluble endoglin (sEng)), lipid and carbohydrate metabolism in maternal plasma, and lipid metabolism in the placenta from assays of fatty acid oxidation, fatty acid esterification, and triglyceride levels in all groups. Antiangiogenic factors sFlt-1, sFlt-1/PlGF ratio, and sEng showed a positive correlation with triglyceride, free fatty acid, and C-peptide maternal serum levels. However, there was no relationship between angiogenic factors and placental lipid metabolism parameters. Free fatty acids were predictive of elevated sFlt-1 and sEng, while C-peptide was predictive of an elevated sFlt1/PlGF ratio. The findings in this study generate a model to predict elevated antiangiogenic factor values and the relationship between them with different products of lipid and carbohydrate metabolism in maternal serum and placenta in preeclampsia. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (FGR) is commonly associated with placental insufficiency and inflammation. Nonetheless, the role played by inflammasomes in the pathogenesis of FGR is poorly understood. We hypothesised that placental inflammasomes are differentially expressed and contribute to the aberrant trophoblast function. Inflammasome gene expression profiles were characterised by real-time PCR on human placental tissues collected from third trimester FGR and gestation-matched control pregnancies (n = 25/group). The functional significance of a candidate inflammasome was then investigated using lipopolysaccharide (LPS)-induced models of inflammation in human trophoblast organoids, BeWo cells in vitro, and a murine model of FGR in vivo. Placental mRNA expression of NLRP3, caspases 1, 3, and 8, and interleukin 6 increased (>2-fold), while that of the anti-inflammatory cytokine, IL-10, decreased (<2-fold) in FGR compared with control pregnancies. LPS treatment increased NLRP3 and caspase-1 expression (>2-fold) in trophoblast organoids and BeWo cell cultures in vitro, and in the spongiotrophoblast and labyrinth in the murine model of FGR. However, the LPS-induced rise in NLRP3 was attenuated by its siRNA-induced down-regulation in BeWo cell cultures, which correlated with reduced activity of the apoptotic markers, caspase-3 and 8, compared to the control siRNA-treated cells. Our findings support the role of the NLRP3 inflammasome in the inflammation-induced aberrant trophoblast function, which may contribute to FGR. [ABSTRACT FROM AUTHOR]

Expression of allergic diseases in very early childhood indicates that early life events play a significant role in childhood allergy development. The developmental origins of allergy hypothesis suggest events initiated in the in-utero period derived from the interaction between maternal, placental, and fetal factors may contribute to childhood allergy susceptibility. Environmental impacts on placental function and fetal programming are imperative in defining illness risk during pregnancy. Fetal programming, a process by which an injury delivered during a critical period of development, causes immediate adaptive responses with long-term consequences on an organism's structure or function. During pregnancy, the maternal immune response is skewed towards Th2-related humoral responses, hence increasing the susceptibility of childhood allergy development. Maternal atopic phenotype markedly increases the probability of her offspring developing an allergic predisposition. Combination of in utero events – which include maternal asthma or infection, and exposures to maternal allergy which changes the placental function – can alter placental cytokine expression and could predispose offspring to an allergic phenotype. All these events may affect embryology and fetal immune system development. Interestingly, the mechanism and role of the in-utero events on the developmental origins of allergy are not clearly understood; this will be addressed in this review. (199 words) [ABSTRACT FROM AUTHOR]

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Ultrasound imaging is a vital tool for exploring in vivo the placental function which is essential to understand pathological phenomena such as preeclampsia or intrauterine growth restriction. As technology advances including ready availability of three-dimensional (3D) probes and novel software, new markers of placental function become possible. The objective of this review was to provide an overview of the new ultrasound markers of placental function with a focus on the potential clinical application of three-dimensional power Doppler (3DPD). A broad-free text literature search was undertaken based on human placental studies and sixty full-text studies were included in this review. Three-dimensional power Doppler is a promising technique to predict preeclampsia in the first trimester. However, the influence of external factors such as body mass index, parameter standardisation and machine settings still need to be addressed. Contrast-enhanced ultrasound is currently reserved for research, because the required injected contrast mediums are not currently approved for use in pregnancy, although the safety data is reassuring. [ABSTRACT FROM AUTHOR]

Background: Biometrical and blood flow examinations are fundamental for assessing fetoplacental development during pregnancy. Guinea pigs have been proposed as a good model to study fetal development and related gestational complications; however, longitudinal growth and blood flow changes in utero have not been properly described. This study aimed to describe fetal and placental growth and blood flow of the main intrauterine vascular beds across normal guinea pig pregnancy and to discuss the relevance of this data for human pregnancy. Methods: Pregnant guinea pigs were studied from day 25 of pregnancy until term (day ~70) by ultrasound and Doppler assessment. The results were compared to human data from the literature. Results: Measurements of biparietal diameter (BPD), cranial circumference (CC), abdominal circumference, and placental biometry, as well as pulsatility index determination of umbilical artery, middle cerebral artery (MCA), and cerebroplacental ratio (CPR), were feasible to determine across pregnancy, and they could be adjusted to linear or nonlinear functions. In addition, several of these parameters showed a high correlation coefficient and could be used to assess gestational age in guinea pigs. We further compared these data to ultrasound variables from human pregnancy with high similarities. Conclusions: BPD and CC are the most reliable measurements to assess fetal growth in guinea pigs. Furthermore, this is the first report in which the MCA pulsatility index and CPR are described across guinea pig gestation. The guinea pig is a valuable model to assess fetal growth and blood flow distribution, variables that are comparable with human pregnancy.

Research Question: What is the relationship between sonographic diagnosis of isolated adenomyosis and placenta-associated obstetric outcomes?, Design: In this 12-year retrospective cohort study (2010-2022), patients presenting with adenomyosis-related symptoms were assessed via ultrasound. The study included 59 women diagnosed with adenomyosis and 62 controls, leading to 203 births (90 in the adenomyosis group and 113 in the control group). Patients with endometriosis, uterine fibroids and anomalies, and those using assisted reproductive technology were excluded. The primary outcome focused on a composite of placenta-associated adverse outcomes, including preterm birth, small-for-gestational-age fetuses, hypertensive disorders of pregnancy, placental abruption and post-partum haemorrhage., Results: No clinically significant differences in demographic characteristics were noted between the two groups. However, the adenomyosis group showed a significantly higher rate of adverse placental function outcomes (27%) compared with the control group (11%, P = 0.005). Adjusted analyses for maternal age, parity and aspirin usage revealed increased risk of hypertensive disorders (adjusted OR 5.91, 95% CI 1.50-30.0; P = 0.017) and adverse placental function outcomes (adjusted OR 3.44, 95% CI 1.53-8.09; P = 0.003) in the adenomyosis group., Conclusion: Adenomyosis is significantly associated with increased risk of adverse placental function outcomes and hypertensive disorders of pregnancy. These findings suggest that adenomyosis may have a distinct impact on pregnancy, underscoring the need for further research to elucidate specific sonographic characteristics of adenomyosis and their effects on placental function., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Obesity is a chronic condition associated with dyslipidemia and insulin resistance. Here, we show that the offspring of obese mothers are dyslipidemic and insulin resistant from the outset. Maternal and cord blood and placental tissues were collected following C-section at term. Patients were grouped as being normal weight (NW, BMI = 18–24.9) or obese (OB, BMI ≥ 30), and separated by fetal sex. We measured plasma lipids, insulin, and glucose in maternal and cord blood. Insulin resistance was quantified using the HOMA-IR. Placental markers of lipid and energy metabolism and relevant metabolites were measured by western blot and metabolomics, respectively. For OB women, total cholesterol was decreased in both maternal and cord blood, while HDL was decreased only in cord blood, independent of sex. In babies born to OB women, cord blood insulin and insulin resistance were increased. Placental protein expression of the energy and lipid metabolism regulators PGC1α, and SIRT3, ERRα, CPT1α, and CPT2 decreased with maternal obesity in a sex-dependent manner (P < 0.05). Metabolomics showed lower levels of acylcarnitines C16:0, C18:2, and C20:4 in OB women's placentas, suggesting a decrease in β-oxidation. Glutamine, glutamate, alpha-ketoglutarate (αKG), and 2-hydroxyglutarate (2-HG) were increased, and the glutamine-to-glutamate ratio decreased (P < 0.05), in OB placentas, suggesting induction of glutamate into αKG conversion to maintain a normal metabolic flux. Newly-born offspring of obese mothers begin their lives dyslipidemic and insulin resistant. If not inherited genetically, such major metabolic perturbations might be explained by abnormal placental metabolism with potential long-term adverse consequences for the offspring's health and wellbeing. [ABSTRACT FROM AUTHOR]

Introduction: Data on placental pathologic features associated with thyreoperoxidase antibodies (TPO Ab) and/or hypothyroidism are limited. The objective of the study was to analyze placental pathologic features of women with TPO Ab positivity.Methods: Prospective case-control observational study of pregnancy outcome among women screened for TPO Ab positivity and/or isolated hypothyroidism (TSH>4mU/L) during the first trimester of pregnancy. Placenta pathologic findings were recorded according to standard classification.Results: The overall rates of TPO Ab positivity and isolated hypothyroidism with negative TPO Ab were 9.6% (86/899) and 2.7% (24/899), respectively. Among TPO Ab positive cases, 77.9% (67/86) and 22.1% (19/86) had TSH ≥2.5mU/L or <2.5mU/L, respectively. Compared to controls, mean first and second trimester uterine artery Doppler pulsatility indices (PI) were higher, placental volume and area were lower among cases with TSH≥2.5mU/L. The rates of fetal growth restriction (FGR)/small for gestational age (SGA) (20/67 versus 8/110, Adjusted Odds Ratio (AdjOR) = 10.8,95%CI = 2.7-44), placental pathological features suggesting decidual vasculopathy (37/67 versus 27/110, AdjOR = 2.7,95%CI = 1.1-6.8) or severe maternal vascular malperfusion (MVM) (22/67 versus 9/110, AdjOR = 5.8,95%CI = 1.6-20.1) were higher among cases with TSH ≥2.5mU/L than in controls. Similar results were obtained comparing overall TPO Ab positive subjects to controls. The increased risk of defective placentation and FGR associated with TPO Ab was independent of simultaneous presence of antinuclear antibodies (ANA) and TSH concentration.Discussion: First trimester TPO Ab positivity was associated with increased rates of abnormal uterine artery Doppler PI and placental features of MVM. This association was independent of TSH concentration and presence of ANA. [ABSTRACT FROM AUTHOR]

Worldwide demand for petroleum products has resulted in increased oil and gas activities in many countries. Conventional and unconventional oil and gas extraction, production, and transport lead to increased levels of petroleum‐derived polycyclic aromatic hydrocarbons (PAHs) in the environment. PAH exposure has profound effects on reproduction by affecting pathways involved in placental trophoblast cell function and impairing normal placental development and function—key contributors to reproductive success. However, other components found in petroleum and wastewaters from oil and gas extraction, including the sulfur‐containing heterocyclic aromatic compounds such as dibenzothiophene (DBT) and its alkylated derivatives, may also impact reproductive success. The goal of this study was to examine the effect of exposure to DBT, a compound commonly detected in the environment, and one of its alkylated analogues, 2,4,7‐trimethyldibenzothiophene (2,4,7‐DBT), on steroidogenic and angiogenic pathways critical for mammalian development in placental trophoblast cells (HTR‐8/SVneo cells). 2,4,7‐DBT but not DBT increased estradiol output in association with increased tube‐like formation (surrogate for angiogenesis). These changes in angiogenesis did not appear to be related to altered expression of the key placental angiogenic gene targets (ANGPTL4, VEGFA, and PGF). Neither compound showed a concentration related effect on progesterone synthesis or its receptor expression. Our results suggest that 2,4,7‐DBT can disrupt key pathways important for placental trophoblast function and highlight the importance of determining the impact of exposure to both parent and alkylated compounds. Further, these data suggest that exposure to sulfur‐containing heterocyclic aromatic compounds may lead to placental dysfunction and impact reproductive success at environmentally relevant levels. Proximity to oil and gas extraction sites has been associated with impaired reproductive success. Oil and gas extraction is associated with increased detection of dibenzothiophene, a sulfur‐containing heterocyclic aromatic compound, and its alkylated congeners in abiotic matrices and wildlife. We demonstrated that 2,4,7‐trimethyldibenzothiophene but not dibenzothiophene caused dysregulated estradiol output and angiogenesis in placental cells. As these outcomes are linked with placental dysfunction, these results highlight the importance of considering the impact of alkylated polycyclic aromatic compounds on mammalian reproduction. [ABSTRACT FROM AUTHOR]

Introduction: In this study, we aimed at quantifying placental concentrations of 22 chemical elements in small fetuses (SGA) as compared with normally grown fetuses (AGA), and to assess the relationship with Doppler markers of placental function.Methods: Prospective cohort study, including 71 SGA fetuses (estimated fetal weight < 10th percentile) and 96 AGA fetuses (estimated fetal weight > 10th percentile), recruited in the third trimester of gestation. The placental concentration of 22 chemical elements was determined by inductively coupled plasma optical emission spectrophotometer (ICP-OES, ICAP 6500 Duo Thermo): aluminum (Al), beryllium (Be), bismuth (Bi), calcium (Ca), cadmium (Cd), cobalt (Co), chrome (Cr), copper (Cu), magnesium (Mg), manganese (Mn), molybdenum (Mo), nickel (Ni), phosphorus (P), lead (Pb), rubidium (Rb), sulfur (S), strontium (Sr), titanium (Ti), thallium (Tl), antimony (Sb), selenium (Se), and zinc (Zn). Placental function was assessed by measuring the following fetal-maternal parameters: Uterine artery Pulsatility Index (UtA PI), Umbilical artery Pulsatility Index (UA PI) and Middle Cerebral artery Pulsatility Index (MCA PI). The association between the chemical elements concentration and study group and the association with Doppler measures were evaluated.Results: SGA was associated with significantly (p < 0.05) lower concentrations of Al (AGA 21.14 vs SGA 0.51 mg/kg), Cr (AGA 0.17 vs SGA 0.12 mg/kg), Cu (AGA 0.89 vs SGA 0.81 mg/kg), Mg (AGA 0.007 vs SGA 0.006 g/100g), Mn (AGA 0.60 vs SGA 0.47 mg/kg), Rb (AGA 1.68 vs SGA 1.47 mg/kg), Se (AGA 0.02 vs SGA 0.01 mg/kg), Ti (AGA 0.75 vs SGA 0.05 mg/kg) and Zn (AGA 9.04 vs SGA 8.22 mg/kg). Lower placental concentrations of Al, Cr, Mn, Se, Ti were associated with abnormal UtA, UA and MCA Doppler.Discussion: Lower placental concentrations of Al, Cr, Cu, Mn, Rb, Se, Ti and Zn are associated with SGA fetuses and abnormal fetal-maternal Doppler results. Additional studies are required to further understand how chemical elements affect fetal growth and potentially find strategies to prevent SGA. [ABSTRACT FROM AUTHOR]

Placental function is essential for fetal development, but it may be susceptible to malnutrition and environmental stressors. To assess the impact of toxic and essential trace elements in placenta on placental function. Toxic metals (cadmium, lead, mercury, cobalt) and essential elements (copper, manganese, zinc, selenium) were measured in placenta of 406 pregnant women in northern Sweden using ICP-MS. Placental weight and birth weight were obtained from hospital records and fetoplacental weight ratio was used to estimate placental efficiency. Placental relative telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) were determined by quantitative PCR (n = 285). Single exposure-outcome associations were evaluated using linear or spline regression, and joint associations and interactions with Bayesian kernel machine regression (BKMR), all adjusted for sex, maternal smoking, and age or BMI. Median cadmium, mercury, lead, cobalt, copper, manganese, zinc, and selenium concentrations in placenta were 3.2, 1.8, 4.3, 2.3, 1058, 66, 10626, and 166 μg/kg, respectively. In the adjusted regression, selenium (>147 μg/kg) was inversely associated with placental weight (B: −158; 95 % CI: −246, −71, per doubling), as was lead at low selenium (B: −23.6; 95 % CI: −43.2, −4.0, per doubling). Manganese was positively associated with placental weight (B: 41; 95 % CI: 5.9, 77, per doubling) and inversely associated with placental efficiency (B: −0.01; 95 % CI: −0.019, −0.004, per doubling). Cobalt was inversely associated with mtDNAcn (B: −11; 95 % CI: −20, −0.018, per doubling), whereas all essential elements were positively associated with mtDNAcn, individually and joint. Among the toxic metals, lead appeared to negatively impact placental weight and cobalt decreased placental mtDNAcn. Joint essential element concentrations increased placental mtDNAcn. Manganese also appeared to increase placental weight, but not birth weight. The inverse association of selenium with placental weight may reflect increased transport of selenium to the fetus in late gestation. • Manganese was positively, and selenium inversely, related to placental weight. • Placental lead was inversely related to placental weight at low selenium levels. • Cobalt was inversely associated with relative mtDNA copy number in placenta. • All micronutrients, individually and joint, were positively related to mtDNA. [ABSTRACT FROM AUTHOR]

Abstract Background Early antiretroviral therapy (ART) during pregnancy has dramatically reduced the risk of perinatal HIV transmission. However, studies have shown an association between premature delivery and the use of ART during pregnancy (particularly protease inhibitor (PI)-based therapies), which could be explained by placental dysfunction. The objective of this study was to evaluate the association of ART (class, duration of exposure and time of initiation) with placental function by using angiogenic factors placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) as biomarkers. Methods Clinical and biological data from 159 pregnant women living with HIV were analyzed. Levels of each biomarker were measured in the first and second trimester of pregnancy. After logarithmic transformation, we compared these using generalized estimating equations according to (a) the type of ART; (b) the duration of exposure to ART; and (c) the time of initiation of ART. Results After adjusting for variables such as ethnicity, maternal age, gestational age, body mass index, parity, smoking status, and sex of the fetus, we found no significant association between the class of ART (PI-based or not) and serum concentrations of PlGF or sFlt-1. Furthermore, no significant association was found between biomarker levels and the duration of ART exposure or the timing of ART initiation (pre- or post-conception). Conclusions This study suggests that first and second trimester angiogenic factor levels are not significantly associated with ART, regardless of the duration or type (with or without PI). These observations seem reassuring when considering the use of ART during early pregnancy.

The dynamic cycling of N-acetylglucosamine, termed as O-GlcNAcylation, is a post-translational modification of proteins and is involved in the regulation of fundamental cellular processes. It is controlled by two essential enzymes, O-GlcNAc transferase and O-GlcNAcase. O-GlcNAcylation serves as a modulator in placental tissue; furthermore, increased levels of protein O-GlcNAcylation have been observed in women with hyperglycemia during pregnancy, which may affect the short-and long-term development of offspring. In this review, we focus on the impact of O-GlcNAcylation on placental functions in hyperglycemia-associated pregnancies. We discuss the following topics: effect of O-GlcNAcylation on placental development and its association with hyperglycemia; maternal-fetal nutrition transport, particularly glucose transport, via the mammalian target of rapamycin and AMP-activated protein kinase pathways; and the two-sided regulatory effect of O-GlcNAcylation on inflammation. As O-GlcNAcylation in the placental tissues of pregnant women with hyperglycemia influences near- and long-term development of offspring, research in this field has significant therapeutic relevance.

The dynamic cycling of N -acetylglucosamine, termed as O-GlcNAcylation, is a post-translational modification of proteins and is involved in the regulation of fundamental cellular processes. It is controlled by two essential enzymes, O-GlcNAc transferase and O-GlcNAcase. O-GlcNAcylation serves as a modulator in placental tissue; furthermore, increased levels of protein O-GlcNAcylation have been observed in women with hyperglycemia during pregnancy, which may affect the short-and long-term development of offspring. In this review, we focus on the impact of O-GlcNAcylation on placental functions in hyperglycemia-associated pregnancies. We discuss the following topics: effect of O-GlcNAcylation on placental development and its association with hyperglycemia; maternal-fetal nutrition transport, particularly glucose transport, via the mammalian target of rapamycin and AMP-activated protein kinase pathways; and the two-sided regulatory effect of O-GlcNAcylation on inflammation. As O-GlcNAcylation in the placental tissues of pregnant women with hyperglycemia influences near- and long-term development of offspring, research in this field has significant therapeutic relevance. [ABSTRACT FROM AUTHOR]

Placental-associated diseases account for most cases of adverse perinatal outcome in developing countries. Doppler evaluation has been incorporated as a predictive parameter at early pregnancy for high-risk placental disease, in the diagnosis and management of those fetuses with impaired intrauterine growth and for the evaluation of fetal wellbeing in those high-risk pregnancies. Uterine Doppler at second trimester predicts most instances of early-onset preeclampsia and intrauterine growth restriction. However, the growing evidence of an effective early propylactic strategy, has turned Uterine Doppler an essential parameter to be included in first trimester predictive algorithms. Umbilical artery Doppler helps in the identification of small-for-gestational-age fetuses at higher risk, and is one of the essential vessels in the assessment of fetal hypoxia impairment, especially in the early cases. It helps in the decision timing for ending the pregnancy improving thus perinatal outcomes. Moreover, in high-risk pregnancies, umbilical artery Doppler has demonstrated to reduce the risk of perinatal deaths and the risk of obstetric interventions. On the other hand, middle cerebral artery Doppler reflects fetal adaptation to hypoxia, and with the cerebroplacental ratio, they improve the detection of fetuses a high risk of adverse perinatal outcome, mostly of those late small fetuses, where most instances of adverse outcome occur in fetuses with normal umbilical artery. Ductus venosous Doppler waveform is a surrogate parameter of the fetal base-acid status. Its use has demonstrated to improve perinatal outcomes, mainly reducing the risk of fetal intrauterine death. Alone or in combination with computerized CTG, it helps tailoring the best moment to end the pregnancy among early cases. [ABSTRACT FROM AUTHOR]

The study of placental lipid metabolism in uncomplicated pregnancies has not been developed in the literature to date. Its importance lies in expanding the knowledge of placental function to enable comparison with pathological pregnancies in future research. The aim of the present study was to compare the lipid metabolic activity and storage of the maternal and fetal sides of the placenta in healthy pregnancies. Moreover, we compare singleton vs. twin pregnancies to determine if placental metabolic needs differ. We analyzed placental explants from uncomplicated pregnancies, 20 from singleton and 8 from bichorial-biamniotic twin pregnancies (n = 28). Six cotyledon fragments were collected from each placenta at different distances from the umbilical cord, three close to the chorionic plate (hereinafter, we will refer to them as "fetal side") and another three close to the anchoring villi into the decidua basalis (referred to as "maternal side"). The samples were analyzed for quantitative assay placental fatty acid oxidation (FAO) and esterification (FAE) activities and triglyceride levels. The location of lipid storage in the chorionic villi was assessed by Oil red-O staining. Placental fatty acid oxidation did not show differences when comparing the maternal and fetal sides of the placenta or between single and twin pregnancies. When comparing placental sides, FAE was increased twofold in the maternal side compared to the fetal side of the placenta (P = 0.013). The tendency for lipogenesis in the placenta was exemplified by the FAE/FAO ratio, which was a 37.1% higher on the maternal side (P = 0.019). Despite this, triglyceride levels were five times higher in the fetal side than in the maternal one (P = 0.024). When analyzing singleton vs. twins, FAE was superior in the fetal side in multiple pregnancies (× 2.6, P = 0.007) and the FAE/FAO ratio was significantly higher in twins than in singleton pregnancies, on both sides of the placenta. Despite this finding, triglyceride levels were similar in twin and singleton pregnancies. Comparing the placentas of twins in the same pregnancy, there were no differences in lipid metabolism (FAO or FAE) or placental triglyceride levels between the two co-twins. Using Oil red-O staining, lipid storage in chorionic villi was found to be located on the syncytiotrophoblast cells and not in the connecting axis. The maternal side of the placenta is more active in the esterification of fatty acids, while the storage of neutral lipids concentrates on the fetal side. Moreover, multiple gestations have increased esterification without changes in the concentration of placental triglycerides, probably due to a higher transfer to the fetal circulation in response to the greater energy demand from twin fetuses. [ABSTRACT FROM AUTHOR]