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Children of parents who were overweight/obese prior to pregnancy face a variety of neurodevelopmental challenges. The goal of this meta-analysis is to compile evidence about the impact of parental overweight/obesity on their children's mental health. The databases Cochrane Library, EMBASE, Pubmed, PsycINFO, and Web of Science were searched until May 2022. The pooled effect size was calculated using the fixed and random effect models. We also performed I2 index, subgroup analyses, sensitivity analyses, quality assessment, and publication bias analysis. The protocol was registered on the PROSPERO database (CRD42022334408). For maternal exposure (35 studies), both maternal overweight [OR 1.14 (95% CI 1.10,1.18)] and maternal obesity [OR 1.39 (95% CI (1.33, 1.45)] were significantly associated with offspring's mental disorders. Maternal pre-pregnancy overweight/obesity increased the risk of attention-deficit/hyperactivity disorder (ADHD) [OR 1.55 (95% CI 1.42,1.70)], autism spectrum disorder (ASD) [OR 1.37 (95% CI 1.22,1.55)], cognitive/intellectual delay [OR 1.40 (95% CI 1.21,1.63)], behavioral problems [OR 1.50 (95% CI 1.35,1.66)] and other mental diseases [OR 1.30 (95% CI 1.23,1.37)]. For paternal exposure (6 studies), paternal obesity [OR 1.17 (95% CI 1.06, 1.30)] but not overweight [OR 1.03 (95% CI 0.95,1.11)] was significantly associated with offspring's mental disorders. Parental overweight/obesity might have negative consequences on offspring's mental health and pre-pregnancy weight control is advised.

Genetic cell-lineage tracing studies in mice are crucial for delineating the contribution of stem and progenitor cells to different cell types, both in disease states and after regenerative therapy. He et al. have developed new genetic lineage-tracing systems that provide more definitive results than the commonly used Cre-based system and show that this new technology can resolve current controversies in the field, as demonstrated by lineage-tracing studies in the heart and liver. The Cre– loxP recombination system is the most widely used technology for in vivo tracing of stem or progenitor cell lineages. The precision of this genetic system largely depends on the specificity of Cre recombinase expression in targeted stem or progenitor cells. However, Cre expression in nontargeted cell types can complicate the interpretation of lineage-tracing studies and has caused controversy in many previous studies. Here we describe a new genetic lineage tracing system that incorporates the Dre– rox recombination system to enhance the precision of conventional Cre– loxP -mediated lineage tracing. The Dre– rox system permits rigorous control of Cre– loxP recombination in lineage tracing, effectively circumventing potential uncertainty of the cell-type specificity of Cre expression. Using this new system we investigated two topics of recent debates—the contribution of c-Kit + cardiac stem cells to cardiomyocytes in the heart and the contribution of Sox9 + hepatic progenitor cells to hepatocytes in the liver. By overcoming the technical hurdle of nonspecific Cre– loxP -mediated recombination, this new technology provides more precise analysis of cell lineage and fate decisions and facilitates the in vivo study of stem and progenitor cell plasticity in disease and regeneration.

Background Obesity and adverse lipid profile leads to female infertility. The cardiometabolic index (CMI) is a promising indicator for predicting obesity-related diseases. The correlation between CMI and female infertility merits further investigation. Methods The data for this study were acquired from the 2013–2020 National Health and Nutrition Examination Survey (NHANES), with 2333 women enrolled. The cardiometabolic index (CMI) of each participant was calculated as the ratio of triglycerides and high-density lipoprotein cholesterol multiplied by waist-to-height ratio. Weighted multivariate logistic regression models were used to assess the independent correlation between the log-transformed CMI and infertility. Subgroup analyses were carried out to assess the reliability of the findings. Interaction tests were employed to determine whether variables affected infertility by interacting with log CMI. Results A total of 2333 participants aged 18–45 years were enrolled, 274 of whom were infertile. Log CMI of the infertility group was significantly higher than that of the non-infertility group ( P  < 0.001). After adjustment for potential confounders, women with higher CMI were at an increased risk of infertility (OR = 2.411, 95% CI: 1.416–4.112), and this correlation was still consistent in subgroups aged under 35 years ( P  < 0.001). Furthermore, restricted cubic spline analysis showed a positive non-linear relationship between log CMI and infertility. Conclusions Cardiometabolic index levels are positively correlated with increased risk of infertility in American females. Our study demonstrates the predictive capacity of CMI for female infertility.

Diabetes mellitus is prevalent among women of reproductive age, and many women are left undiagnosed or untreated 1 . Gestational diabetes has profound and enduring effects on the long-term health of the offspring 2 , 3 . However, the link between pregestational diabetes and disease risk into adulthood in the next generation has not been sufficiently investigated. Here we show that pregestational hyperglycaemia renders the offspring more vulnerable to glucose intolerance. The expression of TET3 dioxygenase, responsible for 5-methylcytosine oxidation and DNA demethylation in the zygote 4 , is reduced in oocytes from a mouse model of hyperglycaemia (HG mice) and humans with diabetes. Insufficient demethylation by oocyte TET3 contributes to hypermethylation at the paternal alleles of several insulin secretion genes, including the glucokinase gene ( Gck ), that persists from zygote to adult, promoting impaired glucose homeostasis largely owing to the defect in glucose-stimulated insulin secretion. Consistent with these findings, mouse progenies derived from the oocytes of maternal heterozygous and homozygous Tet3 deletion display glucose intolerance and epigenetic abnormalities similar to those from the oocytes of HG mice. Moreover, the expression of exogenous Tet3 mRNA in oocytes from HG mice ameliorates the maternal effect in offspring. Thus, our observations suggest an environment-sensitive window in oocyte development that confers predisposition to glucose intolerance in the next generation through TET3 insufficiency rather than through a direct perturbation of the oocyte epigenome. This finding suggests a potential benefit of pre-conception interventions in mothers to protect the health of offspring. Pregestational hyperglycaemia in mothers increases the probability of glucose intolerance in the offspring, an effect controlled by TET3-dependent DNA demethylation of genes involved in insulin secretion.

This study was carried out to explore associations between assisted reproductive technology (ART) and maternal and neonatal outcomes compared with similar outcomes following spontaneously conceived births. We conducted a retrospective cohort study of pregnancies conceived by ART (N = 2641) during 2006–2014 compared to naturally conceived pregnancies (N = 5282) after matching for maternal age and birth year. Pregnancy complications, perinatal complications and neonatal outcomes of enrolled subjects were investigated and analysed by multivariate logistic regression. We found that pregnancies conceived by in vitro fertilization (IVF) were associated with a significantly increased incidence of gestational diabetes mellitus, gestational hypertension, preeclampsia, intrahepatic cholestasis of pregnancy, placenta previa, placental abruption, preterm premature rupture of membranes, placental adherence, postpartum haemorrhage, polyhydramnios, preterm labour, low birth weight, and small-for-date infant compared with spontaneously conceived births. Pregnancies conceived by intracytoplasmic sperm injection (ICSI) showed similar elevated complications, except some of the difference narrowed or disappeared. Singleton pregnancies or nulliparous pregnancies following ART still exhibited increased maternal and neonatal complications. Therefore, we conclude that pregnancies conceived following ART are at increased risks of antenatal complications, perinatal complications and poor neonatal outcomes, which may result from not only a higher incidence of multiple pregnancy, but also the manipulation involved in ART processes.

Background Abnormal one-carbon metabolism has been reported by observational studies to contribute to an increased risk of polycystic ovary syndrome (PCOS) and undesirable reproductive outcomes in women with PCOS. However, the underlying causal associations remain uninvestigated. This study aims to assess the independent causal links between essential substrates, enzymes and cofactors involved in one-carbon metabolism and PCOS, using bidirectional two-sample Mendelian randomization (MR) and Multivariable MR. Results Genetically predicted high levels of folate (OR = 2.92; 95% CI, 1.81 − 3.98; P  = 8.32 × 10 − 4 ), DHFR (OR = 1.25; 95% CI, 1.11–1.41; P  = 1.68 × 10 − 4 ) were causally related to an increased risk of PCOS. Increasing individuals’ long-term exposure to circulating vitamin B 6 would mitigate their risk of developing PCOS (OR = 0.56; 95% CI, 0.34 − 0.91; P  = 6.34 × 10 − 3 ). Additionally, suffering from PCOS was revealed to possibly contribute to vitamin B 12 deficiency (OR = 0.99; 95% CI, 0.98–1.00; P  = 3.61 × 10 –2 ). Conclusions This study integrates metabolomics and genomics to evaluate the causal effects of genetically determined one-carbon metabolism-related factors on PCOS risk, highlighting the critical role of one-carbon metabolism in maintaining reproductive health. These findings underscore the potential of targeting one-carbon metabolism for the prevention and management of PCOS, offering new avenues for clinical interventions. Clinical trial Number not applicable.

Background There has been increasing interest in the relationship between body mass index(BMI) and pregnancy outcomes, especially in women undergoing frozen embryo transfer(FET). Several observational studies have been published, but so far with conflicting results. Methods A systematic review and meta-analysis was conducted according to PRISMA guidelines. Pubmed, Embase, Cochrane Library, Clinicaltrails.gov and Web of Science databases were searched based on established search strategy from inception through January 2021. Results Twelve studies were eligible. In women following FET, high BMI (BMI ≥ 23 kg/m 2 ) was associated with an impaired live birth rate (LBR, OR: 0.89, 95% CI: 0.82–0.96, P  = 0.002), but wasn’t associated with the implantation rate or the clinical pregnancy rate. Subgroup analysis revealed higher LBR for women didn’t complicated by polycystic ovary syndrome (PCOS, OR: 0.96, 95% CI: 0.85–1.08, P  = 0.46) and women with blastocyst transferred (OR: 0.89, 95% CI: 0.68–1.16, P  = 0.40). LBR did not differ between the low BMI group (BMI < 18.5 kg/m 2 ) and the normal weight group. Conclusions Our study showed that high BMI in women is negatively associated with LBR in FET cycles, whereas low BMI isn’t. The results of subgroup analysis implied a need for women with a high BMI to get individualized weight management and treatment. Further evidence is still required to optimize preconception health and develop Nutritional and exercise guidelines.

Mitochondrial function and its regulation within the placenta are critical for maintaining a healthy pregnancy. This study investigated the role of G-protein signaling 12 (RGS12) in placental mitochondrial function and pregnancy outcomes. RGS12 was found to be localized within the mitochondria of placental trophoblast cells. RGS12 knockdown in human placental cells resulted in decreased mitochondrial abundance, impaired oxidative phosphorylation, and reduced antioxidant capacity. Mechanistically, RGS12 enhanced the function of ATP5B, a key mitochondrial enzyme, by promoting its tyrosine phosphorylation. In a mouse model, placental RGS12 deficiency led to reduced tolerance to preterm birth (PTB) challenge, decreased fetal weight, and trophoblast cell death. These adverse effects were associated with diminished ATP synthase activity and activation of the p38MAPK signaling pathway, while restoring RGS12 expression improved the phenotype of mitochondrial dysfunction in placental trophoblast cells. Furthermore, reduced RGS12 expression and impaired mitochondrial function were observed in placentas from cases experiencing PTB. Collectively, these findings provide hitherto undocumented evidence of a specific molecular mechanism by which placental mitochondrial dysfunction contributes to adverse pregnancy outcomes. Our study suggests that RGS12 may represent a novel therapeutic target for improving pregnancy outcomes through its role in regulating placental mitochondrial function.

Studies on humans and animals suggest associations between gestational diabetes mellitus (GDM) with increased susceptibility to develop neurological disorders in offspring. However, the molecular mechanisms underpinning the intergenerational effects remain unclear. Using a mouse model of diabetes during pregnancy, we found that intrauterine hyperglycemia exposure resulted in memory impairment in both the first filial (F1) males and the second filial (F2) males from the F1 male offspring. Transcriptome profiling of F1 and F2 hippocampi revealed that differentially expressed genes (DEGs) were enriched in neurodevelopment and synaptic plasticity. The reduced representation bisulfite sequencing (RRBS) of sperm in F1 adult males showed that the intrauterine hyperglycemia exposure caused altered methylated modification of F1 sperm, which is a potential epigenetic mechanism for the intergenerational neurocognitive effects of GDM.