Associations between OGTT results during pregnancy and offspring TSH levels: a birth cohort study.

BACKGROUND: Limited evidence exists regarding the association between gestational diabetes mellitus (GDM) and elevated levels of thyroid-stimulating hormone (TSH) in newborns. Therefore, this study aimed to investigate the potential risk of elevated TSH levels in infants exposed to maternal GDM, considering the type and number of abnormal values obtained from the 75-gram oral glucose tolerance test (OGTT). METHODS: A population-based, prospective birth cohort study was conducted in Wuhan, China. The study included women who underwent GDM screening using a 75-g OGTT. Neonatal TSH levels were measured via a time-resolved immunofluorescence assay. We estimated and stratified the overall risk (adjusted Risk Ratio [RR]) of elevated TSH levels (defined as TSH > 10 mIU/L or > 20 mIU/L) in offspring based on the type and number of abnormal OGTT values. RESULTS: Out of 15,236 eligible mother-offspring pairs, 11.5% (1,753) of mothers were diagnosed with GDM. Offspring born to women diagnosed with GDM demonstrated a statistically significant elevation in TSH levels when compared to offspring of non-GDM mothers, with a mean difference of 0.20 [95% CI: 0.04-0.36]. The incidence of elevated TSH levels (TSH > 10 mIU/L) in offspring of non-GDM women was 6.3 per 1,000 live births. Newborns exposed to mothers with three abnormal OGTT values displayed an almost five-fold increased risk of elevated TSH levels (adjusted RR 4.77 [95% CI 1.64-13.96]). Maternal fasting blood glucose was independently and positively correlated with neonatal TSH levels and elevated TSH status (TSH > 20 mIU/L). CONCLUSIONS: For newborns of women with GDM, personalized risk assessment for elevated TSH levels can be predicated on the type and number of abnormal OGTT values. Furthermore, fasting blood glucose emerges as a critical predictive marker for elevated neonatal TSH status.

Protein powder supplementation in early pregnancy and the risk of gestational diabetes mellitus: a prospective cohort study.

Objective: Protein powder has attracted attention due to its possible adverse effects. We aimed to investigate the association of protein powder supplementation in early pregnancy with gestational diabetes mellitus (GDM) risk. Methods: We included 6897 participants with singleton pregnancies from a prospective birth cohort. Protein powder supplementation and GDM relationships were examined by unadjusted and multivariable analysis, 1 : 2 propensity score matching, and inverse probability weighting (IPW). A multinomial logistic regression model was used to further explore the effects of protein powder supplementation on the risk of GDM subtypes. Results: Overall, 14.6% of pregnant women (1010) were diagnosed with GDM. In the crude and multivariable analysis before propensity score matching, participants who had received protein powder supplements were more likely to have GDM than women who did not (OR, 1.39 [95% CI: 1.07-1.79]; OR, 1.32 [95% CI: 1.01-1.72]). Protein powder supplementation was significantly associated with a higher GDM risk on IPW analysis (OR, 1.41 [95% CI, 1.08-1.83]), propensity score matching analysis (OR, 1.40 [95% CI, 1.01-1.93]) and multivariable analysis adjusted for propensity score (OR, 1.53 [95% CI, 1.10-2.12]). In the multinomial logistic regression model, protein powder supplementation was only positively associated with the risk of GDM with isolated fasting hyperglycaemia (IFH) in the crude and multivariable models (OR, 1.87 [95% CI: 1.29-2.73]; OR, 1.82 [95% CI: 1.23-2.68]). Conclusions: Protein powder supplementation in early pregnancy is significantly associated with a greater risk of GDM, especially for GDM-IFH. Additional comparative studies are needed to validate these findings.

Maternal paraben exposure and intra-pair thyroid-stimulating hormone difference in twin neonates.

Thyroid hormones are essential for fetal growth and neurodevelopment. The recent frequent use of parabens has raised concerns about their endocrine-disrupting potential. However, the effects of maternal paraben exposure on neonatal thyroid hormone levels are still largely unknown. In our study, a co-twin control design was employed to analyze the relationships between maternal paraben exposure and neonatal thyroid-stimulating hormone (TSH) difference. We collected information from 252 mother-twin pairs from a twin birth cohort in Wuhan, China. Concentrations of six parabens were measured in maternal urine samples collected at < 16, 16-28, and > 28 weeks of gestation. Data of neonatal TSH levels were retrieved from medical records. Multiple informant models were applied to explore the time-specific relationships between paraben exposure and intra-twin TSH difference and to determine the susceptible window of exposure. We found that maternal urinary methyl paraben (MeP) during early pregnancy was positively associated with intra-twin TSH difference (%change = 5.96 %; 95 % confidant interval (CI): 0.04 %, 12.2 %). However, no significant differences were observed for exposure to ethyl paraben (EtP) and propyl paraben (PrP), and the associations between parabens and intra-twin TSH difference did not differ materially across pregnancy. Further, a stratified analysis based on twin zygosity and chorionicity and sex types indicated that the positive association between early pregnancy MeP exposure and intra-twin TSH difference was significant in monochorionic diamniotic (MCDA) twins of female-female fetuses and dichorionic diamniotic (DCDA) twins of opposite-sex. The prospective twin study provides first evidence that MeP exposure in early pregnancy was associated with an increased TSH difference in twin neonates, especially in female fetuses.

Opa interacting protein 5 promotes proliferation and migration of trophoblast cells via activating STAT3 pathway.

Missed abortion, one of the leading causes of maternal and perinatal mortality, is associated with impaired trophoblast function. Opa interacting protein 5 (OIP5) interacts with outer membrane proteins, Opa, to play an important role in mitosis and tumorigenesis. The role of OIP5 in missed abortion was investigated in this study. Firstly, the expression of OIP5 in villous samples from patients with missed abortion was compared with women with normal pregnancies. Result showed that OIP5 was down-regulated in the placental villi from patients with missed abortion. Secondly, human first-trimester extravillous trophoblast-derived cell line (HTR-8/SVneo) was transfected with shRNA targeting OIP5 (shOIP5) or pcDNA-OIP5 (OIP5). Data from MTT and flow cytometry assays demonstrated that knockdown of OIP5 reduced number of viable cells in HTR-8/SVneo, and promoted the cell apoptosis. However, over-expression of OIP5 increased the number of viable cells and suppressed the cell apoptosis in HTR-8/SVneo. Moreover, cell migration of HTR-8/SVneo was inhibited by silencing of OIP5, and OIP5 over-expression enhanced protein expression of matrix metallopeptidase (MMP) 2/9. Lastly, OIP5 contributed to phosphorylation of STAT3 (signal transducer and activator of transcription 3) in HTR-8/SVneo. Inhibition of STAT3 attenuated OIP5 over-expression-induced increase in number of viable cells and migration in HTR-8/SVneo. In conclusion, OIP5 contributed to the proliferation and migration of trophoblast cell through activation of STAT3 signaling.

Naringenin and morin reduces insulin resistance and endometrial hyperplasia in the rat model of polycystic ovarian syndrome through enhancement of inflammation and autophagic apoptosis.

Polycystic Ovary Syndrome (PCOS) is a gynecologic disorder with unsatisfactory treatment options. Hyperandrogenism and insulin resistance (IR) are two symptoms of PCOS. The majority of PCOS patients (approximately 50% to 70%) have IR and moderate diffuse inflammation of varying degrees. We investigated in-vitro and in-vivo effects of naringenin, morin and their combination on PCOS induced endometrial hyperplasia by interfering with the mTORC1 and mTORC2 signaling pathways. The vaginal smear test ensured the regular oestrous cycles in female rats. Serum cytokines (TNF-α and IL-6) were assessed using the ELISA test, followed by in-vivo and in-vitro determination of prominent gene expressions (mTORC1and C2, p62, LC3-II, and Caspase-3 involved in the inflammatory signaling mechanisms through RT-PCR, western bloting, or immunohistochemical analysis. In addition, the viability of naringenin or morin treated cells was determined using flow cytometry analysis. The abnormal oestrous cycle and vaginal keratosis indicated that PCOS was induced successfully. The recovery rate of the oestrous cycle with treatments was increased significantly (P<0.01) when compared to the PCOS model. Narigenin, morin, or a combination of the two drugs substantially decreased serum insulin, TNF-α, IL-6 levels with improved total anti-oxidant capacity and SOD levels (P<0.01). Treatments showed suppression of HEC-1-A cells proliferation with increased apoptosis (P<0.01) by the upregulation of Caspase-3 expression, followed by downregulation of mTORC, mTORC1, and p62 (P<0.01) expressions with improved LC3-II expressions (P<0.05) respectively. The histological findings showed a substantial increase in the thickness of granulose layers with improved corpora lutea and declined the number of cysts. Our findings noticed improved inflammatory and oxidative microenvironment of ovarian tissues in PCOS treated rats involving the autophagic and apoptotic mechanisms demonstrating synergistic in-vitro and in-vivo therapeutic effects of treatments on PCOS-induced endometrial hyperplasia.

CircPSMC3 alleviates the symptoms of PCOS by sponging miR-296-3p and regulating PTEN expression.

Polycystic ovary syndrome (PCOS), the most common female endocrine disease that causes anovulatory infertility, still lacks promising strategy for the accurate diagnosis and effective therapeutics of PCOS attributed to its unclear aetiology. In this study, we determined the abnormal reduction in circPSMC3 expression by comparing the ovarian tissue samples of PCOS patients and normal individuals. The symptom relief caused by up-regulation of circPSMC3 in PCOS model mice suggested the potential for further study. In vitro functional experiments confirmed that circPSMC3 can inhibit cell proliferation and promote apoptosis by blocking the cell cycle in human-like granular tumour cell lines. Mechanism study revealed that circPSMC3 may play its role through sponging miR-296-3p to regulate PTEN expression. Collectively, we preliminarily characterized the role and possible insights of circPSMC3/miR-296-3p/PTEN axis in the proliferation and apoptosis of KGN cells. We hope that this work provides some original and valuable information for the research of circRNAs in PCOS, not only to better understand the pathogenesis but also to help provide new clues for seeking for the future therapeutic target of PCOS.

Effects of Increased Frequency, High Dose, and Pulsatile Oxytocin Regimens on Abnormal Labor Delivery.

BACKGROUND The current guideline for oxytocin regimens in the abnormal labor of delivery is continuous infusion. The objective of the present study was to compare effects and safety measures of various available regimens of oxytocin in abnormal labor delivery. MATERIAL AND METHODS In this clinical experimental study, a total of 900 pregnant women admitted for delivery were randomized into 5 group with 162 each. Pregnant women received oxytocin as continuous administration of 16 mU/min (Group I), 1 mU/min (group II), 4 mU/min (group III), 5 mU/min quarter-hourly (group IV), and through a syringe pump (group V). Measurement of the expense of delivery, the ratio of the instrumental delivery, and the other secondary outcome measures was performed to find the best regimen of oxytocin. The 2-tailed paired t test and Mann-Whitney U test following Dunnett's multiple comparison tests were used at 95% confidence level. RESULTS Pulsatile delivery had least risk of instrumental delivery as compared to continuous infusion (p<0.0001, q=6.663) and normal-frequency low-dose (p<0.0001, q=5.638) of oxytocin. The time required from infusion to delivery was longer for group II (p=0.001, q=2.925), group IV (p<0.0001, q=4.829), and group V (p<0.0001, q=41.456) than for group I. The expense of delivery was: group I < group II < group IV < group III < group V. CONCLUSIONS High-dose and pulsatile preparation of oxytocin had reduced risks of operative delivery vs. continuous administration.