Lan Li

During mammalian oocyte maturation, meiotic arrest takes place during prophase I at the germinal vesicle (GV) stage. Under a specific hormonal milieu, oocytes are reactivated to complete meiosis I and move to a stage of maturity at metaphase II during meiosis II. The regulatory mechanisms underlying this arrest remain incompletely understood. In this study, the epigenomic and transcriptomic data of bovine oocytes at GV and MII stages were integrated to identify differentially expressed genes (DEGs) and dynamics in chromatin accessibility. Firstly, through comparative transcriptomic analysis of bovine oocytes across the GV and MII stages, we observed significant enrichment of DEGs in pathways related to cell cycle regulation and oxidative phosphorylation. Moreover, motif enrichment analysis of differentially accessible regions (DARs) revealed the binding sites of the transcription factor ZBTB33. By combining assay for transposase‐accessible chromatin sequencing (ATAC‐seq) and RNA sequencing (RNA‐seq) datasets, we identified two key meiosis‐associated genes, CCNB1 and PAPOLG . Of note, transcription factor binding site analysis suggested that ZBTB33 may be serve as the regulatory factor for CCNB1 and PAPOLG . In summary, our findings highlight that ZBTB33 potentially regulates bovine oocyte meiosis by orchestrating chromatin accessibility at CCNB1 and PAPOLG . These new findings provide novel insight into the epigenetic regulation of meiotic progression in bovine oocytes.

Primordial follicles form the non-renewable germline reserve in female mammals; their limited number is a key determinant of reproductive lifespan and is crucial for female fertility. Insufficient or parasomnia sleep is common in females, yet little attention is paid to the impact of such sleep disorders during pregnancy on the health of offspring, particularly with regard to ovarian development. In this study, a sleep deprivation (SD) model was established with pregnant mice from 6.5 to 13.5 days of pregnancy. The pregnant mice were subjected to 18 h of SD per day, and the effects on the reproductive function of female offspring and the potential mechanisms were explored. Results showed that SD not only affected maternal weight gain and hormone levels, but also significantly decreased the number of germ cells in female offspring. Furthermore, maternal SD may impact the development of female germ cells by interfering with meiotic progression and inhibiting primordial follicle formation. Importantly, in vitro and in vivo experiments demonstrated that inhibition of ferroptosis improved germ cell loss in offspring caused by maternal SD. Thus, for the first time, our study verified a potential link between germ cell loss during primordial follicle formation and ferroptosis; in theory, this may provide treatment options for reproductive damage in offspring caused by maternal sleep disorders during pregnancy.

Follicle development is a critical process in mammalian reproduction, with significant implications for ovarian reserve and fertility. Stra8 is a known key factor regulating the initiation of meiosis; however, oocyte-like cells still appear in Stra8-deficient mice. Nevertheless, the underlying mechanism remains unclear and requires further investigation. Therefore, we used single-cell RNA sequencing to construct a comprehensive transcriptional atlas of ovarian cells from both wild-type and Stra8-deficient mice at embryonic stages E14.5 and E16.5. With stringent quality control, we obtained a total of 14,755 single cells of six major cell types. A further fine-scale analysis of the germ cell clusters revealed notable heterogeneity between wild-type and Stra8-deficient mice. Compared to the wild-type mice, the deficiency in Stra8 led to the downregulation of meiosis-related genes (e.g., Pigp, Tex12, and Sycp3), and the upregulation of apoptosis-related genes (e.g., Fos, Jun, and Actb), thereby hindering the meiotic process. Notably, we observed that, following Stra8 deficiency, the expression levels of Sub1 and Stk31 remained elevated at this stage. Furthermore, an RNA interference analysis confirmed the potential role of these genes as regulatory factors in the formation of primordial follicle-like cells. Additionally, Stra8 deficiency disrupted the signaling between germ cells and pregranulosa cells that is mediated by Mdk–Sdc1, leading to the abnormal expression of the PI3K/AKT signaling pathway. Together, these results shed light on the molecular processes governing germ cell differentiation and folliculogenesis, emphasizing the complex role of Stra8 in ovarian function.

Birth weight is a key economic trait in pig breeding, affecting pre-weaning survival, growth performance, and overall production efficiency. However, the genetic factors underlying birth weight remain incompletely understood. This study aimed to identify genetic variants associated with birth weight in pigs through a genome-wide association study (GWAS) using 50K SNP genotyping data from 1125 Landrace pigs. Seven significant SNPs linked to birth weight were identified, along with 13 potential candidate genes. To validate these findings, the study population was expanded to include 998 Yorkshire pigs, totaling 2123 individuals. Validation identified two novel SNPs on chromosomes 1 and 16, as well as the previously unreported gene MARCHF11, which was associated with birth weight. These findings enhance the understanding of the genetic architecture underlying birth weight and provide potential targets for molecular marker-assisted selection (MAS). The results offer valuable insights into breeding strategies aimed at improving piglet survival rates and production efficiency. This study underscores the utility of GWAS in identifying key genetic loci for economically important traits in livestock populations.

Rationale: In recent years, nicotinamide adenine dinucleotide (NAD⁺) precursors (Npre) have been widely employed to ameliorate female reproductive problems in both humans and animal models. However, whether and how Npre plays a role in the male reproductive disorder has not been fully clarified.

Zearalenone (ZEN) is well known as a kind of endocrine disruptor whose exposure is capable of causing reproductive toxicity in animals. Cyanidin-3-O-glucoside (C3G) is a derivative of cyanidin and owns multiple biofunctions, and prior efforts have suggested that C3G has therapeutic actions for reproductive diseases. In this article, a ZEN exposure model during primordial follicle assembly was constructed using the in vitro culture platform of neonatal mouse ovaries. We investigated the protective effect of C3G on ZEN-induced ovarian toxicity during primordial follicle assembly in mice, as well as its potential mechanism. Interestingly, we observed that C3G could effectively protect the ovary from ZEN damage, mainly by restoring primordial follicle assembly, which upregulated the expression of LHX8 and SOHLH1 proteins and relieved ZEN-induced DNA damage. Next, to explore the mechanism by which C3G rescued ZEN-induced injury, we performed RNA sequencing (RNA-seq). The bioinformatic analysis illustrated that the rescue pathway of C3G was associated with p53-Gadd45a signaling and cell cycle. Then, western blotting and flow cytometry results revealed that C3G restored the expression levels of cyclin-dependent kinase 6 (CDK6) and cyclin D2 (CCND2) and regulated the ovarian cell cycle to normal. In conclusion, our findings manifested that C3G could alleviate ZEN-induced primordial follicle assembly impairment by restoring the cell cycle involved in p53-GADD45a signaling.