Targeted long-read sequencing enables higher diagnostic yield of ADPKD by accurate PKD1 genetic analysis.

Genetic diagnosis of ADPKD has been challenging due to the variant heterogeneity, presence of duplicated segments, and high GC content of exon 1 in PKD1. In our reproductive center, 40 patients were still genetically undiagnosed or diagnosed without single-nucleotide resolution after testing with a short-read sequencing panel in 312 patients with ADPKD phenotype. A combination of long-range PCR and long-read sequencing approach for PKD1 was performed on these 40 patients.

Association of age at menarche and different causes of infertility: a retrospective study of 7634 women undergoing assisted reproductive technology.

Background: Infertility has become a world-wide public health problem. To identify women in a high-risk of infertility at an early stage when more treatments are available, early risk factors such as age at menarche (AAM) are being investigated. AAM is often used in epidemiological studies as a marker of the timing of pubertal development and the onset of the hypothalamic-pituitary-ovarian axis functions.

Caloric restriction prevents inheritance of polycystic ovary syndrome through oocyte-mediated DNA methylation reprogramming.

Polycystic ovary syndrome (PCOS) is a prevalent metabolic and reproductive endocrine disorder with strong heritability. However, the independent role of oocytes in mediating this heritability remains unclear. Utilizing in vitro fertilization-embryo transfer and surrogacy, we demonstrated that oocytes from androgen-exposed mice (F1) transmitted PCOS-like traits to F2 and F3 generations.

Sex-specific effect of maternal pre-pregnancy BMI on neuropsychiatric development of offspring.

Background/objective: Children of overweight and obese mothers had an increased risk of neuropsychiatric problems. It remains unclear if the association varies by child sex. This study aimed to identify the associations between maternal pre-pregnancy BMI and child sex-specific neuropsychiatric development outcomes during childhood.

Population-level analyses identify host and environmental variables influencing the vaginal microbiome.

The vaginal microbiome is critical for the reproductive health of women, yet the differential impacts exerted by the host and by ambient environmental variables on the vaginal microbiome remain largely unknown. Here, we conducted a comprehensive cross-sectional study of the relationships between the vaginal microbiome and 81 matched host and environmental variables across 6755 Chinese women. By 16S rRNA sequencing, we identified four core vaginal microbiota with a prevalence of over 90% and a total median abundance of 98.

Transgenerational inheritance of diabetes susceptibility in male offspring with maternal androgen exposure.

Androgen exposure (AE) poses a profound health threat to women, yet its transgenerational impacts on male descendants remain unclear. Here, employing a large-scale mother-child cohort, we show that maternal hyperandrogenism predisposes sons to β-cell dysfunction. Male offspring mice with prenatal AE exhibited hyperglycemia and glucose intolerance across three generations, which were further exacerbated by aging and a high-fat diet.

Frozen versus fresh embryo transfer in women with low prognosis for in vitro fertilisation treatment: pragmatic, multicentre, randomised controlled trial.

Objective: To test the hypothesis that a freeze-all strategy would increase the chance of live birth compared with fresh embryo transfer in women with low prognosis for in vitro fertilisation (IVF) treatment.

Design: Pragmatic, multicentre, randomised controlled trial.

Setting: Nine academic fertility centres in China.

No Association of Polycystic Ovary Syndrome with Pancreatic Cancer: A Mendelian Randomization Study.

Unlabelled: Recently, there has been a debate regarding the association between polycystic ovary syndrome (PCOS) and pancreatic cancer (PC). In order to examine the causal relationship between PCOS and PC, we conducted a Mendelian randomization study, which utilized 12 single nucleotide polymorphisms (SNPs) identified from a genome-wide association study (GWAS) meta-analysis that included 10,074 PCOS cases and 103,164 controls of European ancestry as instrumental variables (IVs). The outcome data were obtained from the FinnGen database (including 605 cases and 218,187 controls).

Preimplantation genetic testing for structural rearrangements by genome-wide SNP genotyping and haplotype analysis: a prospective multicenter clinical study.

Background: Preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) has been widely utilized to select euploid embryos in patients carrying balanced chromosomal rearrangements (BCRs) by chromosome copy number analysis. However, reliable and extensively validated PGT-SR methods for selecting embryos without BCRs in large-cohort studies are lacking.

Methods: In this prospective, multicenter, cohort study, carriers with BCRs undergoing PGT-SR were recruited across 12 academic fertility centers within China.

Decreased neurotensin induces ovulatory dysfunction via the NTSR1/ERK/EGR1 axis in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the predominant cause of subfertility in reproductive-aged women; however, its pathophysiology remains unknown. Neurotensin (NTS) is a member of the gut-brain peptide family and is involved in ovulation; its relationship with PCOS is unclear. Here, we found that NTS expression in ovarian granulosa cells and follicular fluids was markedly decreased in patients with PCOS.

snRNA-seq of human ovaries reveals heat shock proteins are associated with obesity related cancer risk.

Background: Obesity significantly impacts female reproductive health and increases the risk of gynecological tumors. However, the specific transcriptional changes that occur in the ovarian microenvironment during obesity-induced stress and the relationship between obesity and ovarian cancer remain unclear.

Methods: Our study investigated the single-cell landscape of the ovarian cortex in individuals with varying BMI levels by snRNA-seq, revealing weight-stage related cellular composition deviations and expression profile irregularities.

MGA loss-of-function variants cause premature ovarian insufficiency.

Although premature ovarian insufficiency (POI), a common cause of female infertility and subfertility, has a well-established hereditary component, the genetic factors currently implicated in POI account for only a limited proportion of cases. Here, using an exome-wide, gene-based case-control analysis in a discovery cohort comprising 1,027 POI cases and 2,733 ethnically matched women controls from China, we found that heterozygous loss-of-function (LoF) variants of MAX dimerization protein (MGA) were significantly enriched in the discovery cohort, accounting for 2.6% of POI cases, while no MGA LoF variants were found in the matched control females.

CHK1 controls zygote pronuclear envelope breakdown by regulating F-actin through interacting with MICAL3.

CHK1 mutations could cause human zygote arrest at the pronuclei stage, a phenomenon that is not well understood at the molecular level. In this study, we conducted experiments where pre-pronuclei from zygotes with CHK1 mutation were transferred into the cytoplasm of normal enucleated fertilized eggs. This approach rescued the zygote arrest caused by the mutation, resulting in the production of a high-quality blastocyst.

TMC7 deficiency causes acrosome biogenesis defects and male infertility in mice.

Transmembrane channel-like (TMC) proteins are a highly conserved ion channel family consisting of eight members (TMC1-TMC8) in mammals. TMC1/2 are components of the mechanotransduction channel in hair cells, and mutations of TMC1/2 cause deafness in humans and mice. However, the physiological roles of other TMC proteins remain largely unknown.

Exposure to polystyrene microplastics during lactational period alters immune status in both male mice and their offspring.

The widespread use of microplastics and their harmful effects on the environment have emerged as serious concerns. However, the effect of microplastics on the immune system of mammals, particularly their offspring, has received little attention. In this study, polystyrene microplastics (PS-MPs) were orally administered to male mice during lactation.

Lactating exposure to microplastics at the dose of infants ingested during artificial feeding induced reproductive toxicity in female mice and their offspring.

Microplastics (MPs) pollution poses a global environmental challenge with significant concerns regarding its potential impact on human health. Toxicological investigations have revealed multi-system impairments caused by MPs in various organisms. However, the specific reproductive hazards in human contexts remain elusive, and understanding the transgenerational reproductive toxicity of MPs remains limited.

The Functions and Application Prospects of Hepatocyte Growth Factor in Reproduction.

Hepatocyte growth factor (HGF) is expressed in multiple systems and mediates a variety of biological activities, such as mitosis, motility, and morphogenesis. A growing number of studies have revealed the expression patterns and functions of HGF in ovarian and testicular physiology from the prenatal to the adult stage. HGF regulates folliculogenesis and steroidogenesis by modulating the functions of theca cells and granulosa cells in the ovary.

Maternal mRNA deadenylation is defective in in vitro matured mouse and human oocytes.

Oocyte in vitro maturation is a technique in assisted reproductive technology. Thousands of genes show abnormally high expression in in vitro maturated metaphase II (MII) oocytes compared to those matured in vivo in bovines, mice, and humans. The mechanisms underlying this phenomenon are poorly understood.