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BackgroundAssisted reproductive technology (ART) has been reported to have negative effects on maternal and neonatal health. Ovulation induction (OI) was reported to be associated with alteration of epigenetic modification of mice embryos, and extinguishing the influence of ovulation induction and in vitro operations on maternal and neonatal health will bring benefits for reducing side effects. The present study aimed to determine whether ovulation induction alone and ART are associated with adverse pregnancy outcomes and whether ART could induce a higher risk than ovulation induction alone.MethodsA total of 51,172 cases with singleton live birth between Jan 2016 and May 2019 at the International Peace Maternal and Child Health Hospital were included in this study. Conception modes documented during registration were classified into natural conception (NC), OI, and ART. Pregnancy outcomes of the three groups with balanced baseline characteristics by propensity score matching were compared. The relative risks of maternal and neonatal outcomes were calculated by logistic regression analysis.ResultsCompared with natural conception, infertility treatments are associated with gestational diabetes (OI: OR 1.72, 95% CI 1.31-2.27; ART: OR 1.67, 95% CI 1.26-2.20), preeclampsia/eclampsia (OI: OR 1.86, 95% CI 1.03-3.36; ART: OR 2.23, 95% CI 1.26-3.92). Even if gestational diabetes, gestational hypertension, and placental problems were adjusted, infertility treatments are associated with birth before 37 weeks (OI: OR 1.99, 95% CI 1.28-3.12; ART: OR 1.70, 95% CI 1.08-2.69), low birth weight (OI: OR 2.19, 95% CI 1.23-3.91; ART: OR 1.90, 95% CI 1.05-3.45), and SGA (OI: OR 2.42, 95% CI 1.20-4.87; ART: OR 2.56, 95% CI 1.28-5.11). ART but not OI is associated with a higher risk of birth before 34 weeks (OR:3.12, 95% CI 1.21-8.05). By comparing the OI group with the ART group, we only found that ART could induce a higher ratio of placental problems (5.0%, 26/518 vs 2.1%, 11/519, p

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is a hereditary kidney disorder mostly caused by mutations in PKD1 or PKD2 genes. Here, we report thirteen ADPKD males with infertility and investigated the sperm morphological defects associated with PC1 disruption.MethodsTargeted next-generation sequencing was performed to detect PKD1 variants in patients. Sperm morphology was observed by immunostaining and transmission electron microscopy, and the sperm motility was assessed using the computer-assisted sperm analysis system. The Hippo signaling pathway was analyzed with by quantitative reverse transcription polymerase chain reaction (qPCR) and western blotting in vitro.ResultsThe ADPKD patients were infertile and their sperm tails showed morphological abnormalities, including coiled flagella, absent central microtubules, and irregular peripheral doublets. In addition, the length of sperm flagella was shorter in patients than in controls of in in. In vitro, ciliogenesis was impaired in Pkd1-depleted mouse kidney tubule cells. The absence of PC1 resulted in a reduction of MST1 and LATS1, leading to nuclear accumulation of YAP/TAZ and consequently increased transcription of Aurka. which might promote HDAC6-mediated ciliary disassembly.ConclusionOur results suggest the dysregulated Hippo signaling significantly contributes to ciliary abnormalities in and may be associated with flagellar defects in spermatozoa from ADPKD patients.

IntroductionAnti-Müllerian hormone (AMH) level has long been considered as a serum biomarker of ovarian reserve clinically, while emerging data suggest that serum AMH level may also predict pregnancy outcomes. However, whether pregestational serum AMH levels are related to perinatal outcomes among women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles is unknown.ObjectiveTo explore the association between different AMH levels and perinatal outcomes in women with live births in IVF/ICSI.MethodsThis multicenter retrospective cohort study was conducted among three different provinces in China, from January 2014 to October 2019. A total of 13,763 IVF/ICSI cycles with 5657 live-delivery pregnant women and 6797 newborns were recruited. Participants were categorized into three groups according to the 75th (high) percentile of serum AMH concentration. Perinatal outcomes were compared among groups. Subgroup analyses were conducted based on the number of live births.ResultsAmong women with singleton deliveries, low and high AMH levels increased the risk of intrahepatic cholestasis of pregnancy (ICP) (aOR1 = 6.02, 95%CI: 2.10-17.22; aOR2 = 3.65, 95%CI:1.32-10.08) and decreased the risk of macrosomia (aOR1 = 0.65, 95%CI:0.48-0.89; aOR2 = 0.72, 95%CI:0.57-0.96), while low AMH reduced the risk of large for gestational age (LGA, aOR=0.74, 95%CI:0.59-0.93) and premature rupture of membrane (PROM, aOR=0.50, 95%CI:0.31-0.79)compared with the average AMH group. In women with multiple deliveries, high AMH levels increased the risks of gestational diabetes mellitus (GDM, aOR=2.40, 95%CI:1.48-3.91) and pregnancy-induced hypertension (PIH, aOR=2.26, 95%CI:1.20-4.22) compared with the average AMH group, while low AMH levels increased the risk of ICP (aOR=14.83, 95%CI:1.92-54.30). However, there was no evidence of differences in preterm birth, congenital anomaly, and other perinatal outcomes among the three groups in both singleton and multiple deliveries.ConclusionsAbnormal AMH levels increased the risk of ICP regardless of the number of live births for women undergoing IVF/ICSI, while high AMH levels increased the risks of GDM and PIH in multiple deliveries. However, serum AMH levels were not associated with adverse neonatal outcomes in IVF/ICSI. The underlying mechanism warrants further investigation.

ContextMaternal lipid levels affect birthweight and the long-term health of the offsprings. However, this association could be influenced by genetic and other common factors.ObjectiveThis work aimed to explore the relationship between maternal lipid levels and birthweight of two pregnancies in the same mother.MethodsIn this population-based cohort study, 705 women and their 1 410 offsprings were included. From an initial sample of women with more than one singleton birth in the database, we made the following exclusions: missing data for pre-pregnancy BMI, pregnancy weight gain, birthweight and lipid values; maternal age less than 19 or older than 44 years old; gestational age < 37 weeks or > 41weeks, gestational diabetes mellitus/diabetic. In the second and third trimesters, serum samples were collected for the determination of fasting total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels. Then we assessed the association between maternal lipids and birthweight.ResultsInfants of women whose 2nd-trimester TC increased by 10th-20th percentile (-0.92~-0.56 mmol/L) from 1st to 2nd pregnancy were 239.69 (62.32~417.06) g lighter at birth than were infants of women those of 40th-50th percentile (-0.20~-0.03 mmol/L). Parity, gestational age, neonatal gender, maternal pre-pregnancy body mass index, maternal weight gain, and 3rd-trimester TC and HDL-C were all associated with higher birth weight. Every unit increase in TC in the third trimester increases birthweight by 53.13 (14.32 ~91.94) g.ConclusionMaternal TC level is associated with birthweight independent of shared genes. TC may be used to guide diet and predict birthweight combined with ultrasound and other indicators.

IntroductionElevated maternal serum lipid concentrations have been related to an adverse intrauterine environment and lead to abnormal birth weight.ObjectiveIn this study, we aimed to explore the association between maternal lipid profiles during early pregnancy and birth weight with stratified pre-pregnancy body mass index (BMI).MethodsThis retrospective cohort study was based on a large population from two major maternity centers in Shanghai, China. We included 57,516 women with singleton live birth between January 2018 and October 2020. All of the enrolled women had fasting lipid concentrations measured in early pregnancy. The primary outcomes were birth weight and risks of adverse birth outcomes, including macrosomia, large for gestational age (LGA), low birth weight (LBW), and small for gestational age (SGA).ResultsHigher maternal concentrations of total cholesterol (TC), triglyceride (TG), and low-density cholesterol (LDL-c) in early pregnancy were associated with increased birth weight. Ln transformed TG and levels exhibited a positive association with LGA and macrosomia (OR = 1.33, 95% CI: 1.25, 1.42 and OR = 1.37, 95% CI: 1.24, 1.52) and showed a negative relationship with SGA (OR = 0.73, 95% CI: 0.62, 0.85). High TG (>75th percentile, 1.67 mmol/L) group also showed higher risks of LGA and macrosomia (OR = 1.21, 95% CI: 1.15, 1.28 and OR = 1.20, 95% CI: 1.10, 1.31) and decreased prevalence of SGA (OR = 0.71, 95% CI: 0.61, 0.83). Moreover, significant combined effects of pre-pregnancy BMI and lipid profiles on LGA and macrosomia were identified.ConclusionsElevated maternal lipid profiles in early pregnancy are associated with higher birth weight and increased risks of LGA and macrosomia. We propose that serum lipid profiles in early pregnancy and pre-pregnancy BMI could serve as screening indexes for high-risk women.

A potential correlation between polycystic ovary syndrome (PCOS) and asthma, used to be identified as diseases originating from two independent systems, has been supported by increasing evidence. From an epidemiological perspective, mounting studies have confirmed that women suffering from PCOS exhibit increased susceptibility to asthma. Meanwhile, PCOS and asthma seem to share several mutual pathological conditions, such as metabolic disorders, hormonal fluctuation, proinflammatory state, etc. Here, we further elucidate the correlation between asthma and PCOS by focusing on the internal common pathophysiology and adverse influences on women’s health. Understanding the internal connection between PCOS and asthma may shed light on developing new prevention and control strategies to fight against these conditions.

BackgroundSubclinical hypothyroidism (SCH) during pregnancy has been associated with multiple adverse maternal and neonatal outcomes. However, the potential benefits of levothyroxine (LT4) supplementation remain controversial. Variations across studies in diagnostic criteria for SCH may, in part, explain the divergent findings on the subject. This study aimed to assess the effect of LT4 treatment on pregnancy and neonatal outcomes among pregnant women who were diagnosed as SCH based on the most recent diagnostic criteria.MethodsWe conducted a systematic review and meta-analysis of the literature published from inception to January 2020. The search strategy targeted the studies on pregnancy and neonatal outcomes following LT4 treatment in women with SCH based on 2017 American Thyroid Association diagnostic criteria. Pooled effect sizes were estimated using fixed and random effect models, according to the absence or presence of heterogeneity which was assessed using the I-squared statistic. Sources of heterogeneity and the stability of results were evaluated through sensitivity analysis.ResultsOf the 2781 identified references, 306 full-text articles were screened for eligibility. Finally, 6 studies including a total of 7955 participants were retained for analysis. Summary effect estimates indicated that pregnant women with SCH treated with LT4 had a lower risk of pregnancy loss [odds ratio (OR) = 0.55, 95% confidence interval (CI): 0.43-0.71], preterm birth (OR=0.63, 95% CI: 0.41-0.98) and gestational hypertension (OR = 0.78, 95% CI: 0.63-0.97) than those in control group.ConclusionLT4 treatment in pregnant women with SCH may reduce the risk of pregnancy loss, preterm delivery and gestational hypertension.

Traditionally, the anteroventral periventricular (AVPV) nucleus has been the brain area associated with luteinizing hormone (LH) surge secretion in rodents. However, the role of the other population of hypothalamic kisspeptin neurons, in the arcuate nucleus (ARC), has been less well characterized with respect to surge generation. Previous experiments have demonstrated ARC kisspeptin knockdown reduced the amplitude of LH surges, indicating that they have a role in surge amplification. The present study used an optogenetic approach to selectively stimulate ARC kisspeptin neurons and examine the effect on LH surges in mice with different hormonal administrations. LH level was monitored from 13:00 to 21:00 h, at 30-minute intervals. Intact Kiss-Cre female mice showed increased LH secretion during the stimulation period in addition to displaying a spontaneous LH surge around the time of lights off. In ovariectomized Kiss-Cre mice, optogenetic stimulation was followed by a surge-like secretion of LH immediately after the stimulation period. Ovariectomized Kiss-Cre mice with a low dose of 17β-estradiol (OVX+E) replacement displayed a surge-like increase in LH release during period of optic stimulation. No LH response to the optic stimulation was observed in OVX+E mice on the day of estradiol benzoate (EB) treatment (day 1). However, after administration of progesterone (day 2), all OVX+E+EB+P mice exhibited an LH surge during optic stimulation. A spontaneous LH surge also occurred in these mice at the expected time. Taken together, these results help to affirm the fact that ARC kisspeptin may have a novel amplificatory role in LH surge production, which is dependent on the gonadal steroid milieu.

Mounting evidence has shown that intrauterine hyperglycemia exposure during critical stages of development may be contributing to the increasing prevalence of diabetes. However, little is known about the mechanisms responsible for offspring metabolic disorder. In this present study, we explored intrauterine hyperglycemia exposure on fetal pancreatic metabolome, and its potential link to impaired glucose tolerance in adult offspring. Here, using a GDM mouse model, we found the metabolome profiling of pancreas from male and female fetus showing altered metabolites in several important pathways, including 5-methylcytosine, α-KG, branched-chain amino acids, and cystine, which are associated with epigenetic modification, insulin secretion, and intracellular redox status, respectively. This finding suggests that intrauterine exposure to hyperglycemia could cause altered metabolome in pancreas, which might be a metabolism-mediated mechanism for GDM-induced intergenerational diabetes predisposition.

ObjectiveSex steroids are thought to contribute to the pathogenesis of osteoarthritis (OA). This study investigated the causal role of sex steroids in site- and sex-specific OA and risk of joint replacement surgery using the Mendelian randomization (MR) method.MethodsInstrumental variables for estradiol, dehydroepiandrosterone sulfate, testosterone (T), and dihydrotestosterone (DHT) were selected. We used the inverse variance weighting (IVW) approach as the main MR method to estimate causal effects based on the summary-level data for OA and joint replacement surgery from genome-wide association studies (GWAS).ResultsA positive causal association was observed between serum T level and risks of hip OA (odds ratio [OR]=1.558, 95% confidence interval [CI]: 1.193–2.034; P=0.001) and hip replacement (OR=1.013, 95% CI: 1.008–1.018; P=2.15×10−8). Serum DHT level was also positively associated with the risk of hip replacement (OR=1.011, 95% CI: 1.006–1.015; P=4.03×10−7) and had potential causality with hip OA (OR=1.398, 95% CI: 1.054–1.855; P=0.020).ConclusionsSerum T and DHT levels may play causal roles in the development of hip OA and contribute to the risk of hip replacement, although the underlying mechanisms require further investigation.