Reproductive Sciences最新文献

Obesity leads to menstrual dysfunction by impacting the "hypothalamic-pituitary-ovarian axis" in women, which can result in polycystic ovary syndrome (PCOS). The differentially expressed genes (DEGs) between the PCOS and control groups were identified using a public database, By intersecting these DEGs with key module genes and obesity related genes (ORGs), we obtained 75 differentially expressed ORGs (DE-ORGs). Further screening using machine learning led to the identification of five potential diagnostic biomarkers: CPT1A, LARS2, GSTP1, TREX1, and PILRB. The expression levels of biomarkers exhibited notable variations between the control and PCOS group, with area under curve (AUC) values exceeding 0.89 for all biomarkers, confirming their role as molecular diagnostic biomarkers for PCOS. The AUC of nomogram achieved 1, indicating its perfect predictive capability for PCOS occurrence. Single-cell analysis highlighted the crucial roles of GSTP1 and epithelial cells in the early stages of PCOS development. This study clarifies the roles of these diagnostic biomarkers, offering a theoretical foundation for the clinical assessment and treament of the disease.

Environmental and genetic factors are related to the pathogenesis of preeclampsia (PE). Cytochrome P450 2E1 (CYP2E1) is crucial for the metabolism of endogenous and xenobiotic substances, possibly involved in the pathophysiology of PE. This study explored the association between CYP2E1 96-bp insertion/deletion (I/D) and rs2031920 (C-1054T) genetic variants and the risk of PE in 335 patients with PE and 1301 healthy pregnant women. The CYP2E1 C-1054T variant was linked to an elevated risk of PE according to the dominant, genotype, and allele genetic models (P < 0.05). The genotype TT + CT remained a significant predictor of PE in the logistic regression model including age, gestational age, and body mass index at delivery (OR = 1.606, 95% CI: 1.137-2.286; P = 0.007). Moreover, the combined genotype TT + CT/II + ID of the C-1054T and 96-bp I/D variants further heightened the risk of PE, with the combined genotype DD/CC serving as the reference category (OR = 2.383, 95% CI: 1.381-4.106, P = 0.002). Furthermore, patients with the -1054T allele had lower serum albumin levels and total antioxidant capacity, and more severe proteinuria than those with the CC genotype (P < 0.05), and patients with the 96-bp I allele had a relatively higher atherosclerosis index than those with the DD genotype (P = 0.057). No significant differences in genotype frequencies of PE with severe features, platelet count, serum hepatic enzyme activities and creatinine levels were observed according to the different genotypes (P > 0.05). We conclude that the T allele of the C-1054T variant and its integration with the I allele of the 96-bp I/D variant in CYP2E1 are linked to an elevated risk of PE in Chinese women.

Ex utero embryo culture is one of the important tasks that has not been completely solved. In the first part of the current review, we focus on potential roles ex utero mammalian embryo culture could play, such as in infertility treatment or ex utero embryo treatment. Particularly, we discuss ex utero genetic therapy of embryos for correction and prevention of congenital pathologies. We also discuss the benefits of ex utero embryo culture in comparison to the traditional surrogacy programs and review its potential influence on social aspects. In the second part, we discuss key methods for ex utero embryo culture, their limitations, bottlenecks and blank points. Moreover, we analyze methods of artificial embryo production using stem cells and possible uses of such embryos (including those that reproduce stages of postimplantation development) in scientific research. We discuss the risks of using the described technologies and possible approaches that will avoid these risks.

The genetic etiology is unknown for 30-40% of men with congenital bilateral absence of the vas deferens (CBAVD) and 70% of those with congenital unilateral absence of the vas deferens (CUAVD). The study aimed to investigate the genetic etiology of CBAVD/CUAVD, both with and without renal anomalies, in individuals who are negative for CFTR pathogenic variants. We included 19 cases of congenital absence of vas deferens (CAVD) that were negative for CFTR variants on Sanger sequencing. Whole-exome sequencing (WES) was performed in 16 men with CAVD. Targeted resequencing was carried out in a total of 19 CAVD cases [16 CAVD cases for which WES was performed and an additional 3 CBAVD cases without renal anomalies]. A novel, hemizygous ADGRG2 pathogenic variant (c.1706 C > T; p.T569I) was identified in two men with CBAVD without renal anomalies. Additionally, we detected pathogenic variants in AR, NCKPAL1, FSHR, and SLC26A4 genes in CBAVD without renal anomalies. Pathogenic variants were detected in FREM1, WNT2B, and TBX6 genes in CBAVD men with renal abnormalities. No variants were detected in CUAVD with renal anomalies. In addition to a novel pathogenic variant in the ADGRG2 gene, we report novel candidate genes AR, NCKPAL1, FSHR, and SLC26A4, for CBAVD. We identified variants in the FREM1, WNT2B, and TBX6 genes in CBAVD with renal anomalies. ADGRG2 testing could be useful for appropriate genetic counselling for the X-linked transmission of the molecular defect in CFTR-negative CBAVD. We recommend whole-exome sequencing for genetic screening of CBAVD for CFTR, ADGRG2, and other candidate genes prior to undergoing Intracytoplasmic sperm injection (ICSI).

Male infertility remains a significant global reproductive health challenge, frequently attributed to genetic mutations impairing spermatogenesis and sperm function. This narrative review aims to explore the genetic and molecular underpinnings of male infertility and evaluate the emerging role of Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-associated protein 9 (CRISPR/Cas9) genome editing as a diagnostic and therapeutic tool, while addressing its associated ethical, technical, and safety considerations. A Comprehensive literature search was conducted across PubMed, Scopus, Web of Science databases, covering studies published between September 1992 and April 2025. Keywords included "male infertility," "genetic causes of male infertility," "genome editing," "CRISPR/Cas9 and male infertility," "genome editing in male reproduction," "ethical concerns of CRISPR," and "future fertility treatments." Eligible studies focused on genetic correction strategies, spermatogonial stem cell applications, off-target effects, mosaicism, and ethical implications of gene editing. The review synthesizes current knowledge on genetic and epigenetic etiologies of male infertility. It discusses the therapeutic potential of CRISPR/Cas9 in correcting these defects and restoring fertility in preclinical models. Critical challenges, including off-target gene editing, germline mosaicism, long-term safety, and ethical debates surrounding human germline modification, were examined. The review also considers future advancements in genome editing and artificial sperm development. CRISPR/Cas9 represents a transformative platform in reproductive medicine with promising implications for treatment of genetically linked male infertility. However, its clinical translation demands rigorous validation, transparent ethical deliberation, and robust regulatory frameworks. Future innovations combining genome editing, regenerative biology, and precision diagnostics may revolutionize fertility care, but must proceed with caution to ensure safety, efficacy, and ethical integrity.

Abnormal development of granulosa cells is widely recognized as a critical factor contributing to polycystic ovary syndrome (PCOS). However, the precise etiology and underlying mechanisms of this disorder remain largely elusive. Accumulating evidence suggests that dysregulation of microRNAs (miRNAs) plays a pivotal role in the pathogenesis of PCOS. In this study, we systematically investigated the functional impact of miR-30c-5p on the human cumulus cells (CCs). Our findings revealed that miR-30c-5p suppresses the proliferation and induces apoptosis in the human granulosa-like tumor cell line (KGN) via targeting SIRT1. Notably, the expression level of miR-30c-5p was significantly elevated in PCOS patients compared to healthy controls, whereas the expression of SIRT1 was markedly reduced. A negative correlation was observed between miR-30c-5p and SIRT1 expression. Mechanistically, upregulation of miR-30c-5p led to decreased expression of SIRT1 and Bcl-2 proteins, while simultaneously enhancing the expression of Bax proteins. Furthermore, our data confirmed that SIRT1 serves as a direct target of miR-30c-5p. Collectively, these results indicate that miR-30c-5p promotes apoptosis of GCs by directly targeting SIRT1, thereby representing a novel molecular target for improving GC dysfunction in PCOS patients.

Background: Cervical cancer (CC) is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer-related deaths in women worldwide, however, the treatment options for advanced CC are limited. Therefore, there is an urgent need in the clinic for reliable prognostic models to guide clinical decision-making.

Methods: We conducted differential gene expression analysis on cervical cancer samples and normal samples to obtain differentially expressed genes (DEGs). We used WGCNA analysis to identify the most relevant module associated with cervical cancer and intersected with DEGs to obtain cervical cancer-related genes. We then constructed a protein-protein interaction (PPI) network using these genes and identified core genes using the Hubba plugin in Cytoscape software. Subsequently, we built a prognostic model using the identified cervical cancer-related genes in combination with the TCGA database. GSE44001 was used to verify the accuracy of the model. We performed a single-gene survival analysis on the genes involved in model construction.

Results: We obtained 52 cervical cancer-related genes and 22 core genes (DNA2, CEP55, GINS1, RFC4, KIF14, GINS2, MYBL2, KIF4A, RAD54L, KNTC1, SPAG5, MELK, CENPE, MCM2, NCAPH, MCM5, ASPM, HELLS, DTL, FOXM1, TOP2A, CDC45). We successfully constructed a prognostic model using cervical cancer-related genes. The comprehensive analysis showed that the constructed prognostic model could effectively predict the prognosis of cervical cancer patients, with AUC values of 0.858, 0.802, and 0.797 for 1, 3, and 5 years in the training group, respectively. The results were consistent in the validation using the GSE44001 dataset. Single-gene survival analysis showed that APOD was an independent prognostic biomarker for cervical cancer.

Conclusion: APOD is a prognostic biomarker for cervical cancer, and the prognostic model constructed by identified cervical cancer-related genes can successfully distinguish the prognosis of patients with cervical cancer.

Cervical endometriosis is an uncommon site and a distinctive entity of this enigmatic disease. It has a different clinical presentation, more difficult diagnosis and dissimilar management approach. Endometriosis of the cervix can be classified into superficial, deep and polypoid.Superficial cervical endometriosis may appear on cervical smears as atypical glandular cells and may present with intermenstrual spotting or postcoital bleeding. It is usually treated by colposcopic loop excision or cryocautery. Patients with deep cervical endometriosis complaint mainly of chronic pelvic pain and treated like traditional deep infiltrating endometriosis of the pelvis. The polypoid form frequently presents with abnormal vaginal bleeding and treated by polypectomy in most of the cases.The case presented in this report was a presexual 13-year-old adolescent girl with a large polypoid cervical endometriosis (9 cm in maximum dimension) who presented with abnormal vaginal bleeding. Complete resection of the polyp was performed in two sessions of transhymenal vagino-resectoscopy. Diagnosis was only confirmed by histopathological examination. This was a rare example of the possible role of hysteroscopy in the management of some forms of endometriosis.