Single-cell, spatial and bulk transcriptome data analysis revealed LINC00467-mediated Sertoli cell ferroptosis is a potential therapeutic target and biomarker for azoospermia.

Human spermatogenesis is an important physiological process related to programmed cell death. However, which type of programmed cell death playing a key role in normal and abnormal human spermatogenesis remains obscure. This study integrated single-cell, bulk RNA and spatial transcriptome data analysis and found that the ferroptosis signal plays a potential role in spermatogenesis and significantly elevate in testicular samples from humans with non-obstructive azoospermia (NOA) due to various factors.

Homozygous variant in JARID2 causes female infertility characterized by compromised blastulation efficiency.

Background: Impaired embryonic developmental competence is a critical determinant of assisted reproductive technology (ART) failure, yet current genetic diagnostics primarily address complete early embryonic arrest, leaving partial developmental defects unexplained, such as compromised blastulation efficiency (CBE). Jumonji and AT-rich interaction domain containing 2 (JARID2), encoding a chromatin-modifying factor essential for histone methylation regulation, emerges as a novel candidate in this context.

Results: We identified a homozygous JARID2 missense variant (c.

Empagliflozin reduces left ventricular mass increase and improves cardiomyocyte hypertrophy after 5/6 nephrectomy.

Left ventricular hypertrophy (LVH) is a common cardiac complication in patients with cardiorenal syndrome. Empagliflozin has demonstrated cardio-renal protective effects in clinical studies, potentially linked to reductions in left ventricular mass (LVM). Using a 5/6 nephrectomy rat model to induce cardiorenal syndrome, we administered two doses of Empagliflozin (3 mg/kg/day and 15 mg/kg/day) via gavage for 95 days, with Telmisartan as a positive control.

Genetic rare disease prevention and control: Family-based screening and reproductive interventions in Changsha.

Rare diseases pose a significant public health challenge, particularly in underserved regions such as China, where genomic diagnostic services and post-diagnosis management remain limited. This study assessed the effectiveness of a rare disease screening program in Changsha, China, which enrolled 85,391 couples between January 2022 and June 2023. Among these participants were 1,414 suspected high-risk couples undergoing genetic testing, with 562 found to be at high risk of having a child with a rare disease, yielding a positive rate of 39.

A novel PADI6 splice-site variant induces non-canonical GC-AG splicing and embryonic arrest in humans.

Early embryonic arrest (EEA) represents the predominant cause of assisted reproductive technology (ART) failure. PADI6 was a disease-associated gene identified for EEA. To date, 42 likely causal PADI6 variants have been documented, predominantly located in exonic regions with clustering outside the N-terminal domain.

Biallelic variants in DLGAP5 cause spindle assembly defects and human early embryonic arrest.

Study Question: What effects do DLGAP5 defects have on human early embryo development?

Summary Answer: DLGAP5 deficiency disrupts normal spindle assembly through its interaction with TACC3, leading to female infertility characterized by recurrent early embryonic arrest (REEA).

What Is Known Already: REEA is a significant contributor to failures in assisted reproductive technology. While genetic factors play a crucial role, known gene variants account for only a small proportion of affected individuals, leaving many underlying genetic factors yet to be elucidated.

METTL5 deficiency induces oligoasthenoteratozoospermia via impaired 18S rRNA mA methylation in humans and mice.

Recent studies have highlighted RNA modifications as integral regulators of gene expression during spermatogenesis. Ribosomal RNAs (rRNAs) are the most abundant RNA in cells, while the function and clinical relevance of rRNA modifications in spermatogenesis remain poorly understood. Here, we identified 4 pathogenic heterozygous variants of METTL5 in 1,427 patients with male infertility characterized as oligoasthenoteratozoospermia (OAT).

CCN5 Drives Leydig Cell Aging and Testicular Dysfunction: Insights into Fibrosis, Lipid Dysregulation, and Therapeutic Potential.

Leydig cells' (LCs') senescence is an important reason for the decline of testicular function in elderly men. Cellular communication network factor 5 (CCN5) regulates lipid metabolism and cellular fibrosis through multiple mechanisms. However, its role in LCs' aging and the underlying molecular mechanisms remain unclear.

Marital Adjustment as a Mediator Between Emotional Suppression and Self-Compassion in Women Aged 35+ Undergoing In Vitro Fertilization-Embryo Transfer: A Cross-Sectional Observational Study.

This study aimed to investigate the pathways of emotional suppression among women aged 35 years and older undergoing in vitro fertilization-embryo transfer (IVF-ET) and to provide a theoretical basis for developing personalized programs to reduce emotional suppression. A convenience sample of 225 women aged ≥35 years undergoing IVF-ET at a reproductive centre between May 1st and September 30th, 2023, was selected. The participants completed a self-designed general information questionnaire, the Emotional Inhibition Scale (EIS), the Locke-Wallace Marriage Adjustment Test (MAT), and the Self-Compassion Scale (SCS).

Oxford Nanopore third generation sequencing for analysis of FMR1 5'UTR CGG repeat expansions.

Objective: Fragile X syndrome is mainly caused by the expansion of GC-rich cytosine-guanine-guanine (CGG) repeat in FMR1 5'UTR region, as well as rare gene point mutations or deletions in its open reading frame. Currently, third-generation long-read sequencing is a potential technology for simultaneously detecting CGG repeat expansions, point mutations, and deletions. However, a major challenge remains in obtaining the target long-fragment CGG repeat region with ultra-high GC content for sequencing.

Preimplantation genetic testing for facioscapulohumeral dystrophy caused by contractions of 4q35 D4Z4 repeats.

Research Question: Preimplantation genetic testing for monogenic diseases (PGT-M) is based on mutation testing combined with linkage analysis; so, how should PGT-M for patients with facioscapulohumeral dystrophy type 1 (FSHD1) be conducted when direct mutation testing is unavailable and specific linked markers are lacking?

Design: Patients with a definite FSHD1 diagnosis who intended to prevent the transmission of the condition to their children were recruited in the Reproductive and Genetic Hospital of CITIC-Xiangya, China between May 2021 and December 2023. Familial genetic risk was evaluated using Bionano, 4q haplotyping and whole-exome sequencing. Linkage markers near the causative 4q35 D4Z4 repeats were identified using targeted sequencing and MicroSeq.

Prior COVID-19 infection increases degenerated oocytes but does not affect IVF outcomes: a prospective cohort study.

Background: The global health crisis of coronavirus disease 2019 (COVID-19) continues to impact people of all age groups worldwide. Recent studies increasingly support that COVID-19 infection may affect reproductive function, causing subfertility and infertility. It is a prospective observational cohort study conducted in the Reproductive and Genetic Hospital of CITIC-Xiangya.

Longitudinal change and causal relationship between gut microbiota and gestational diabetes mellitus.

Background: Recent studies have increasingly shown the connection between gut microbiome and gestational diabetes mellitus (GDM). However, most studies only focused on a single time point during pregnancy.

Methods: We conducted a nested case-control study in a follow-up cohort, recruiting 52 patients with GDM and 52 healthy controls.

GMNN mutations cause female infertility characterized by preimplantation embryo arrest through regulating DNA re-replication.

Preimplantation embryo arrest is a common cause of female infertility and recurrent failure of assisted reproductive technology. However, its genetic basis is largely unrevealed. Geminin, encoded by the GMNN gene, plays an important role in preventing DNA re-replication by inhibiting CDT1.

Fecal microbiota transplantation for hypertension: an exploratory, multicenter, randomized, blinded, placebo-controlled trial.

Background: On the basis of the contribution of the gut microbiota to hypertension development, a novel strategy involving fecal microbiota transplantation (FMT) has been proposed to treat hypertension, but its efficacy has not been investigated in the clinic.

Methods: In a randomized, blinded, placebo-controlled clinical trial (2021/03-2021/12, ClinicalTrials.gov, NCT04406129), hypertensive patients were recruited from seven centers in China, and received FMT or placebo capsules orally at three visits.

Identification of nonfunctional CABS1 causing fertilization failure and male infertility in humans: a case report.

Purpose: This study aimed to identify new genes associated with total fertilization failure (TFF) by intracytoplasmic sperm injection (ICSI).

Methods: Whole-exome sequencing (WES) was performed on a patient presenting with TFF by ICSI. To assess the spermatozoa's morphology and ultrastructure, hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM) were employed.

The lncRNA SENCR knockdown alleviates vascular calcification via miR-4731-5p by suppressing endoplasmic reticulum stress.

Background: Accumulation of calcium phosphate crystals is associated with vascular calcification (VC); however, the mechanism that promotes VC remains unclear. Accumulating evidence indicates that smooth muscle and endothelial cell-enriched migration/differentiation-associated lncRNA (SENCR) exerts a critical role in VC. This work focuses on the molecules involved in β-glycerophosphate-induced osteogenic differentiation of vascular smooth muscle cells (VSMCs) through SENCR epigenetic modification of Runx2 in an endoplasmic reticulum stress (ERS)-dependent manner.

RGS14 binds to GNAI3 and regulates the proliferation and apoptosis of human spermatogonial stem cells by affecting PLPP2 expression and MAPK signaling.

Background: Non-obstructive azoospermia (NOA) represents a severe form of male infertility, characterized by the absence of sperm in the ejaculate due to impaired spermatogenesis. Spermatogonial stem cells (SSCs), which ensure continuous sperm production, are critical for maintaining male fertility. Despite their importance, the molecular mechanisms governing SSC fate determination and their role in NOA pathogenesis remain incompletely understood.

CITED2 Binding to EP300 Regulates Human Spermatogonial Stem Cell Proliferation and Survival Through HSPA6.

Spermatogonial stem cells (SSCs) are essential for the initiation and continuation of spermatogenesis, a process fundamental to male fertility. Despite extensive studies on mouse SSCs, the mechanisms governing self-renewal and differentiation in human SSCs remain to be elucidated. This study investigated the regulatory mechanisms of SSCs by analyzing single-cell sequencing data from the GEO dataset of human testis.

Maternal transcription factor OTX2 directly induces SETD1A and promotes embryonic genome activation in human pre-implantation embryos.

Early embryonic development is controlled by maternal factors originating from mature oocytes. The zygotic genome is activated from a transcriptionally quiescent state through a process called embryonic genome activation (EGA), which involves the depletion and clearance of maternal factors. However, the mechanism by which maternal factors regulate EGA and embryonic development, particularly in humans, remains elusive.

CCDC80 Protects against Aortic Dissection and Rupture by Maintaining the Contractile Smooth Muscle Cell Phenotype.

Aortic dissection (AD) is a life-threatening medical emergency characterized by adverse vascular remodeling. Coiled-coil domain-containing protein 80 (CCDC80) plays an essential role in regulating cardiovascular remodeling. This study aims to define the role of CCDC80 in the formation and development of AD.

Novel mutations in ZMYND15 are associated with male infertility with oligozoospermia/azoospermia.

Purpose: This study aimed to identify the genetic causes of male infertility associated with oligozoospermia/azoospermia in two unrelated Chinese families.

Methods: Whole-exome sequencing (WES) and Sanger sequencing were performed on peripheral blood samples from three infertile individuals with reduced sperm counts. Semen analysis data were collected, and sperm morphology was evaluated using hematoxylin and eosin staining, along with transmission electron microscopy.

Women with FSHR-inactivating mutations causing resistant ovarian syndrome benefit from oocyte in-vitro maturation.

Research Question: Is in-vitro maturation (IVM) of oocytes effective for treating women with resistant ovarian syndrome (ROS) carrying biallelic FSHR-inactivating mutations?

Design: Three patients with ROS were recruited for this study. Candidate pathogenic mutations were identified using whole-exome sequencing (WES). A cAMP production assay was performed to evaluate the effects of these mutations.

COVID-19 vaccination and pregnancy-induced hypertension risk in women undergoing assisted reproduction.

Study Question: Does COVID-19 vaccination affect the risk of pregnancy-induced hypertension (PIH) in women undergoing ARTs, and does this risk differ based on vaccine type (inactivated vs recombinant) and timing relative to embryo transfer?

Summary Answer: Women who received inactivated COVID-19 vaccines before undergoing ART had a significantly increased risk of developing PIH, particularly when vaccinated with two or more doses or when embryo transfer occurred within 1 month of vaccination.

What Is Known Already: COVID-19 vaccination during pregnancy reduces the risk of severe COVID-19 illness with no significant safety concerns for the mother or fetus. PIH is a common complication in ART pregnancies, particularly in older women and those with higher BMI, but the effects of different COVID-19 vaccine types on PIH risk in ART pregnancies remain unclear.

No differences in IVF pregnancy outcomes following hysteroscopic polypectomy using a manual hysteroscopic tissue removal device versus conventional resection.

Background: To compare in-vitro fertilization and embryo transfer (IVF-ET) pregnancy outcomes following endometrial polypectomy using either a manual mechanical hysteroscopic tissue resection device (mHTR) or traditional mechanical resection with scissors or polyp graspers resection.

Methods: This retrospective study examined 189 infertile patients who had undergone polypectomy prior to IVF-ET at Reproductive and Genetic Hospital of CITIC-XIANGYA. Patients undergoing polypectomy using manual mHTR resection were compared to those having the procedure through traditional mechanical resection.