This study aimed to define the nonlinear relationship between maternal free thyroxine (FT4) levels in early pregnancy and the risk of preeclampsia. This study used a large-scale retrospective cohort of 46 592 women with singleton pregnancies. Thyroid function parameters and preeclampsia outcomes were collected. A restricted cubic spline model analyzed the nonlinear relationship between FT4 levels and preeclampsia risk. Odds ratios were calculated using multivariable logistic regression, adjusting for confounders. Preeclampsia risk was also assessed based on thyroid disease classifications. Sensitivity analyses validated the robustness of the results. The study found a U-shaped relationship between FT4 levels in early pregnancy and preeclampsia risk. The risk was lowest at 15 pmol/l, with a significant increase as FT4 deviated from this value, especially at lower FT4 levels. A physiological optimal range of 13.9-17.3 pmol/l was identified. Compared to women in this range, low FT4 levels (< 11.7 pmol/l) had a significantly higher risk of preeclampsia (adjusted odds ratio, aOR = 2.23). Even women with FT4 at the lower end of the normal range (11.7-13.9 pmol/l) had increased risk (aOR = 1.26), indicating a latent high-risk group. In traditional thyroid classification, only hypothyroxinemia was a significant independent risk factor. Sensitivity analyses confirmed result stability. This study reveals that low FT4 level is an independent risk factor for preeclampsia, with a dose-dependent effect. These findings support targeted prevention strategies and provide a new approach for precise preeclampsia prevention.

Identifying critical windows and sex-specific effects of periconceptional exposure to fine particulate matter and temperature on fetal growth trajectories: A longitudinal birth cohort study.

Adequate folate is essential to prevent neural tube defects; therefore, supplementation with folic acid is widely recommended for women during preconception and early pregnancy. However, the potential risks associated with excessive intake of folic acid and/or an elevated blood folate concentration are not well recognized. The aim of this review was to evaluate the potential adverse health outcomes associated with excessive intake of folic acid and/or an elevated blood folate concentration during preconception and pregnancy. The review included studies that measured intake of folic acid via dietary sources and supplements, and/or quantified serum/plasma and red blood cell folate concentrations. Excessive intake of folic acid and an elevated blood folate concentration were associated with several adverse outcomes. The most notable association was with gestational diabetes mellitus, where elevated intake of folic acid and a high blood folate concentration were found to increase the risk. Excessive intake of folic acid supplements and a high blood folate concentration were associated with gestational diabetes mellitus, and adverse neurodevelopmental issues in offspring, as well as large-for-gestational-age infants and higher birth weight. Clear definitions of safe upper limits for intake of folic acid and blood folate concentration are needed urgently to prevent potential adverse outcomes.

Maternal exposure to childhood maltreatment is linked to alterations in the trajectories of steroid hormones during pregnancy.

Recombinant humanized type III collagen attenuates recurrent spontaneous abortion by regulating stromal cell decidualization and reinforcing protective immune microenvironment at the maternal-fetal interface.

The oxidative stress-triggered activation of the PKC-Nrf2-G6PD pathway drives Benz(a)pyrene-induced endometrial stromal cell proliferation.

Temporal changes in circulating miRNAs following gestational diabetes diagnosis: a pilot longitudinal study.

Systematic review and meta-analysis of birth weight and prenatal exposure to perfluoroundecanoic acid.

Embryo implantation and decidualization are essential to the establishment and maintenance of pregnancy. However, the underlying mechanism on embryo implantation and decidualization remains unclear. Although the regulation and role of hypothalamic corticotropin-releasing hormone (CRH) during early pregnancy have been extensively studied, uterine CRH is still poorly defined. This study examined CRH expression in mouse uterus during early pregnancy and evaluated the regulation and role of CRH during embryo implantation and decidualization. Immunofluorescence was used to show CRH protein concentrations in mouse uterus. The inhibitor for CRH receptor CRHR1 and recombinant CRH protein were applied to analyze the function of CRH on mouse in vitro decidualization. CRH is expressed in luminal epithelium of mouse uterus from Day 1 to Day 4 of pregnancy. At implantation site on Day 5 of pregnancy, CRH is strongly localized in primary decidua. Verucerfont, a CRHR1 inhibitor, significantly suppresses mouse in vitro decidualization. Our results indicated that CRH is strong expressed in primary decidua and should play a role during mouse decidualization. This result should shed lights on understanding the underlying mechanism during embryo implantation and decidualization.

Association between Vitamin D levels and autoimmune thyroid disease in early pregnancy.

Astrocytes play an essential role in the control of gonadotropin-releasing hormone (GnRH) neurons. However, limited information is available in non-conventional animal models. This study aimed to explore the hypothalamic astrocyte distribution in the plains vizcacha (Lagostomus maximus), a South American hystricomorph rodent with distinctive reproductive physiology, and to analyze their spatial relationship with GnRH neurons throughout the life cycle. Female plains vizcachas were evaluated during non-pregnancy (ovulating and non-ovulating) and pregnancy (early-, mid-, and late-pregnant). Plasma levels of estradiol (E2), progesterone (P4), and luteinizing hormone (LH) were determined. Astrocytes were assessed by glial fibrillary acidic protein (GFAP) immunohistochemistry in hypothalamic regions involved in reproductive control, including the medial preoptic area (mPOA), arcuate nucleus (ARC), and median eminence (ME). Their spatial relationship with GnRH-immunoreactive neurons and fibers was also analyzed. Pregnancy was associated with marked hormonal changes, including significantly elevated E2 levels and dynamic variations in P4 and LH (P < 0.01). Astrocyte distribution was largely conserved across life stages in the mPOA and ME, whereas a significant reduction in GFAP-immunoreactive area was detected in the ARC during early pregnancy. Close appositions between astrocytic processes and GnRH neurons were observed in ovulating non-pregnant and pseudo-ovulating mid-pregnant animals. In the ME, very intimate contacts between astrocytic processes and GnRH fibers in the palisade layer were detected exclusively during pregnancy. In conclusion, these findings reveal a steroid-dependent plasticity of hypothalamic astrocytes and support a key role for astrocyte-GnRH neuron interactions in the regulation of reproductive neuroendocrine function during gestation in the plains vizcacha.

T helper cell cytokines and complement pathway are modulated in the ovine duodenum during early pregnancy

Preeclampsia (PE) is a complex pregnancy disorder associated with early placental hypoxia, oxidative stress, and impaired angiogenic signaling. Melatonin and soluble tumor necrosis factor like weak inducer of apoptosis (sTWEAK) contribute to antioxidant and vascular pathways, whereas their receptors, melatonin receptor 1A (MTNR1A), melatonin receptor 1B (MTNR1B), and fibroblast growth factor-inducible 14 (Fn14), may be subject to epigenetic regulation. This study assessed serum melatonin and sTWEAK levels in parallel with promoter methylation of MTNR1A, MTNR1B, and Fn14 in early gestation. A mixed design cohort was recruited between 13 and 20 weeks of gestation. A total of 198 pregnant women were categorized as pregnant control, high risk, or preeclamptic at enrollment time. Serum melatonin and sTWEAK were measured by enzyme-linked immunosorbent assay (ELISA). Promoter methylation of MTNR1A, MTNR1B, and Fn14 was assessed using methylation-specific PCR with semi quantitative densitometry. Serum sTWEAK levels were significantly lower in high-risk and preeclamptic women, whereas melatonin levels showed a downward trend without reaching statistical significance. Promoter methylation of MTNR1A and Fn14 was elevated in both high-risk and preeclamptic groups, whereas MTNR1B showed no notable differences. Multivariate analysis revealed that lower sTWEAK (OR 0.837; 95% confidence interval [CI] 0.782-0.896; p<0.001) and higher Fn14 methylation (OR 0.935; 95% CI 0.882-0.992; p=0.027) were independently associated with hypertensive outcomes. Additionally, higher Fn14 methylation in early pregnancy was observed in high-risk women who later developed hypertensive disorders. Early pregnancy hypermethylation of MTNR1A and Fn14, but not MTNR1B, was observed in high-risk and PE women and co-occurred with a significantly reduced sTWEAK level and non-significantly reduced serum melatonin, suggesting epigenetic modulation of antioxidant and angiogenic pathways in women at risk for PE. These findings establish associations rather than causation and require validation using quantitative assays in multicenter cohorts before clinical translation.

Adiponectin modulates endometrial prostaglandin production during early pregnancy in pigs: An in vitro study.

We sought to evaluate the association between the timing of new-onset hypertensive disorders of pregnancy (HDP) development (ie, antepartum, intrapartum, or postpartum) and the risk of incident hypertension 2-7 years after delivery in nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be) and nuMoM2b-HHS (the nuMoM2b Heart Health Study). This is a secondary analysis of a multisite prospective observational cohort study conducted at eight clinical sites that enrolled nulliparous individuals with singleton pregnancies in their first trimester who were followed during pregnancy and subsequently underwent a cardiovascular screening visit 2-7 years after delivery. For this analysis, we excluded individuals with prepregnancy chronic hypertension in their nuMoM2b pregnancy. We compared rates of stage 1 hypertension (blood pressure 130/80 mm Hg or higher or use of antihypertensive medications) at the 2-7 year postpartum study visit based on the timing of the onset of HDP (categorized as antepartum, intrapartum, postpartum) with no HDP (referent). Multivariable logistic regression models adjusted for baseline covariates (age, insurance, tobacco use, diabetes, and early pregnancy body mass index [BMI]) were used to generate adjusted odds ratios (aOR) and 95% CIs. Interaction analysis was performed to evaluate effect modification by the presence of severe features of HDP. P <.05 was considered statistically significant. Of 4,342 individuals included in this analysis (mean age 27.0 years [SD 5.6 years]), 23.2%% (n=1,007) had new-onset HDP. Among those with HDP, 53.6% (n=540) were diagnosed antepartum, 42.4% (n=427) were diagnosed intrapartum, and 4.0% (n=40) were diagnosed postpartum. At a mean follow-up of 3.2±0.9 years after delivery, the frequency of incident hypertension was elevated regardless of whether HDP occurred antepartum (37.6%, n=203), intrapartum (26.0%, n=111), or postpartum (40.0%, n=16) (compared with no HDP [16.5%, n=550]). After adjustment for maternal age, insurance type, tobacco use, prepregnancy diabetes, and early pregnancy BMI, the risk of chronic hypertension remained elevated regardless of when HDP was diagnosed, although the risk was higher when it developed antepartum (aOR 2.40, 95% CI, 1.95-2.95) or postpartum (aOR 2.90, 95% CI, 1.49-5.64) compared with when it developed intrapartum (aOR 1.55, 95% CI, 1.21-1.97; referent no HDP, P <.01 for all). New-onset HDP, regardless of whether it is diagnosed antepartum, intrapartum, or postpartum, is associated with an increased risk of incident hypertension 2-7 years after delivery, compared with individuals without HDP during their first birth. Greater awareness of cardiovascular disease risk after HDP-even when HDP is diagnosed during labor or postpartum-is needed to appropriately risk stratify and help prevent hypertension after delivery. ClinicalTrials.gov, NCT02231398.

Associations of co-exposure to organophosphate flame retardants and pesticides with maternal thyroid function in early pregnancy: Findings from the Shanghai Birth Cohort.

The significant cross-reactivity between bovine, ovine, and caprine pregnancy-associated glycoproteins (PAGs) enables the adaptation of bovine-specific diagnostics for use in other ruminants; consequently, the Alertys OnFarm Pregnancy Test (AOFPT)-a blood-based lateral flow assay-provides a rapid and practical solution for pregnancy detection directly at the animal's head under field conditions. This study evaluated to assess and validate the performance of AOFPT in goats at days 21 and 28 post-mating, by comparing the results with serum progesterone (P4) analysis and using transabdominal ultrasonography (TAUS) as the gold standard. The study involved 85 Kilis goats, five months post-partum. Estrus was synchronized using an 11-day progestagen device, d-cloprostenol, and PMSG. Whole blood and serum samples were collected on Days 21 and 28 post-mating. AOFPT was performed on-farm immediately after collection. For validation, serum progesterone concentrations were measured via electrochemiluminescence immunoassay, and TAUS was performed on Days 35 and 42, with Day 42 findings serving as the gold standard. Results indicated that on Day 21, AOFPT sensitivity, specificity, positive predictive value, and negative predictive value were 79.4%, 93.8%, 98.2%, and 51.7%, respectively. By Day 28, these metrics reached 100%, 81.3%, 95.8%, and 100%. Statistical agreement between AOFPT and the reference method was K = 0.55 (82.14%) on Day 21 and K = 0.87 (96.43%) on Day 28 (p <0.001). Median ± interquartile range (IQR) of P4 concentrations were 5.95±2.60ng/mL on day 21 and 6.92 ± 2.93ng/mL on Day 28. AOFPT-identified pregnant goats exhibited significantly higher P4 levels (p < 0.001) than non-pregnant goats on Day 21 (5.98 ± 3.21vs. 4.05 ± 5.46) and Day 28 (6.84 ± 3.06vs. 0.75 ± 5.96). AOFPT demonstrated accuracy and reliability closely matching P4 measurements and the reference method. This test provides a practical tool for early on-farm pregnancy diagnosis in goats, potentially enhancing reproductive management and productivity in dairy goat farms and large herds.

Olfactory perception is a key component in the elicitation of disgust. General disgust sensitivity fluctuates during pregnancy as part of the behavioral immune system's protective mechanisms, but it is currently unknown whether a similar pattern applies also specifically to odor-elicited disgust. This longitudinal study examined changes in body odor disgust sensitivity during pregnancy and the postpartum period among 276 women, recruited in health centers. Participants completed questionnaires focused on body odor disgust, general pathogen disgust, anxiety, and nausea and vomiting in pregnancy at multiple points from early pregnancy until six months postpartum. The results revealed that body odor disgust sensitivity peaked in the first trimester, declined through the later trimesters, and reached its lowest point in the early postpartum period before increasing again at six months postpartum. This trajectory was found for body odor disgust directed at both own and other person's bodies. Importantly, body odor disgust sensitivity could not be explained solely by general pathogen disgust sensitivity, which suggests a distinct role for olfactory disgust in pregnancy. Our findings support the Compensatory Prophylaxis Hypothesis, which highlights the adaptive increase in disgust sensitivity during the especially vulnerable period of early pregnancy. The postpartum decline in body odor disgust may reflect either desensitization to infant odors or reduced social exposure. Future research could further explore the physiological and psychological factors which contribute to these changes.

Maternal metabolic bariatric surgery is associated with improved maternal cardiovascular function and an altered adipokine (adiponectin and leptin) levels. The aim of this study was to investigate whether adipokine levels mediate the improvement in maternal cardiovascular function reported in pregnant women with previous metabolic bariatric surgery. The study included 41 pregnant women with previous metabolic bariatric surgery and 41 pregnant women without metabolic bariatric surgery but with similar early pregnancy body mass index (BMI). All participants underwent cardiac function assessment using two-dimensional echocardiography, at 11-14, 20-24 and 30-32 weeks of gestation. Maternal blood, collected at these three visits, was used for measurement of maternal adiponectin and leptin. Mixed-effects model analysis was used to assess the differences in adiponectin and leptin between groups, after adjustment for time, maternal age, ethnic group, parity, method of conception, BMI, smoking, gestational age at measurement and development of gestational diabetes mellitus. Pearson's correlation was used to assess the correlation of maternal adiponectin and leptin levels with cardiac indices. Overall, maternal adiponectin levels were higher in the post-metabolic bariatric surgery group, compared to the no surgery group (p = 0.008). However, leptin levels did not differ between groups (p = 0.76). Adiponectin levels were not associated with indices of maternal cardiac function including haemodynamics, cardiac geometry, diastolic, systolic and longitudinal function (p > 0.05). In contrast, maternal leptin levels positively correlated with maternal cardiac output in both the no surgery and post-metabolic bariatric surgery groups (p < 0.01 and p = 0.02, respectively). Although pre-pregnancy maternal metabolic bariatric surgery is associated with an improvement in maternal cardiac function, maternal adiponectin and leptin levels alone are unlikely to contribute to this improvement.

Nuangong Tiaojing Formula ameliorates luteal phase defect by restoring ovarian-uterine axis function via regulating inflammatory-apoptotic cascade.