Jun Wang

The unresolved mechanisms underlying heterosis in beef cattle production traits hinder the optimization of crossbreeding strategies. In this study, we generated Wagyu × Hereford hybrid cattle (F1) and observed significantly enhanced growth rates compared to purebred Hereford controls, prompting further investigation into the epigenetic regulatory basis of heterosis in bovine muscle development. Combined microRNA‐seq and RNA‐seq profiling of the longissimus dorsi muscle identified 17 differentially expressed miRNAs and 489 differentially expressed genes (DEGs), enabling the construction of a comprehensive miRNA–mRNA regulatory network. Notably, decreased expression of bta‐novel‐miR‐357 (novel‐miR‐357) and increased expression of S100A2 (S100 Calcium‐Binding Protein A2) mRNA were observed in the hybrid cattle. Functional assays in primary bovine myoblasts demonstrated that novel‐miR‐357 and siS100A2 inhibited cell proliferation and promoted apoptosis. Dual‐luciferase reporter assays confirmed that novel‐miR‐357 directly binds to the 3′UTR of S100A2 mRNA, establishing a targeted regulatory relationship. Furthermore, novel‐miR‐357 was shown to inhibit proliferation and promote apoptosis of bovine myoblasts through targeting S100A2 mRNA. These findings reveal a novel epigenetic regulatory axis (novel‐miR‐357/ S100A2 mRNA) involved in early muscle development and provide an important molecular mechanism for deeper understanding of the epigenetic regulatory processes underlying heterosis in cattle. Nevertheless, given the polygenic complexity of heterosis, it is important to recognize that this pathway likely represents only one of several contributing factors to this complex trait.

Background: The cellular basis of testicular development and spermatogenesis for the extreme sperm density in chickens (100-fold higher than mammals) remains poorly defined. A comprehensive understanding of the molecular characteristics driving poultry testicular development is crucial for explaining this enhanced spermatogenic capacity. Results: Here, we first established a single-cell transcriptome profile of chicken testes from hatching to maturity, identifying the dynamic transcriptional characteristics of germ cell fate transition and exploring the developmental characteristics of Sertoli cells and Leydig cells. Multi-species comparisons revealed a higher proportion of germ cells and the unique adaptations of Sertoli cells in chicken testes. Most importantly, our results demonstrated that Sertoli cells dominated in somatic composition of mature chicken testes, and proliferating Sertoli cells persisted in chicken testes even after sexual maturity, while no proliferating Sertoli cells in mammals. We also found a richer interaction network between chicken testicular cells, especially the specific activation of Sertoli cell interaction signals, such as TGF-β, BMP, EGF, and activin. These adaptations of Sertoli cells may support the spermatogenic superiority in chickens. Additionally, our results indicated that cAMP responsive element binding protein 5 ( CREB5 ) played a crucial role in maintaining the maturation and function of chicken Sertoli cells, and circadian rhythm promoted testosterone secretion and the development of Leydig cells. Conclusion: Our study revealed that the sustained proliferative capacity of Sertoli cells, their enriched signaling network, and the regulatory roles of CREB5 and circadian rhythms collectively represented unique testicular adaptations in chickens. These findings may hold extraordinary significance in understanding the molecular characteristics of poultry testicular development, and provide a plausible framework for explaining enhanced spermatogenesis in poultry. Graphical

Recently, evidence has indicated that mastitis is closely associated with the ruminal dysbiosis caused by subacute ruminal acidosis (SARA) and subsequent l

Epigenetics studies heritable changes in gene expression without altering the DNA sequence and is involved in diverse biological processes. In male reproduction, Leydig cells, the main site of testosterone synthesis, play an important role in maintaining the reproductive process. However, the role of epigenetics in the mechanism of testosterone synthesis in Leydig cells is still not well understood. This review systematically describes how classic epigenetic modifications such as DNA methylation, RNA methylation, histone modification, and non-coding RNA regulate the testosterone synthesis process of Leydig cells in different species. Accumulating evidences revealed that epigenetics can regulate the process of testosterone synthesis in Leydig cells. In future, we aim to provide new ideas for male reproduction by investigating the relationship between testosterone synthesis mechanisms and epigenetics.

Sperm freezability exhibits marked individual variability, yet the mechanisms remain unclear. Using bulls as the experimental model, we integrated proteomic (sperm) and metabolomic (seminal plasma) analyses of high-freezability (HF) and control (CF) bulls to identify key biomarkers associated with sperm freezability. Post-thaw motility and membrane integrity were significantly higher in HF bulls (p < 0.05). Sperm proteome analysis revealed upregulated antioxidant proteins (PRDX2, GSTM4), heat shock proteins (HSP70, HSP90), and key enzymes in arginine and proline metabolism (PRODH, LAP3). Seminal plasma metabolomics revealed elevated spermine in HF bulls. Meanwhile, we found that spermine abundance was positively correlated with post-thaw motility, as well as with the expression levels of both PRODH and LAP3 (r > 0.6, p < 0.05). Functional validation demonstrated that 200 μM spermine supplementation in cryopreservation extenders enhanced post-thaw motility, kinematic parameters (VAP, VSL, VCL), membrane integrity, and acrosome integrity (p < 0.05). Concurrently, spermine enhanced antioxidant enzyme (SOD, CAT, GSH-Px) activity and reduced ROS and MDA levels (p < 0.05). Our study reveals a spermine-driven antioxidant network coordinating sperm–seminal plasma synergy during cryopreservation, offering novel strategies for semen freezing optimization.

Mercury, a prevalent heavy metal, negatively impacts oocyte maturation. However, the exact mechanism by which methylmercury chloride (MMC) affects this process remains elusive. The present study found that MMC administration triggered meiotic failure in oocytes by disrupting cumulus cell expansion, leading to compromised spindle apparatus and altered chromosomal architecture, which are crucial for oocyte development. This disruption is characterized by abnormal microtubule organization and defective chromosome alignment. Additionally, MMC exposure caused oxidative stress-induced apoptosis due to mitochondrial dysfunction, as indicated by decreased mitochondrial membrane potential, mitochondrial content, mitochondrial DNA copy number, and adenosine triphosphate levels. Proteomic analysis identified 97 differentially expressed proteins, including P62, an autophagy marker. Our results confirmed that MMC induced autophagy, particularly through the hyperactivation of the mitochondrial autophagy to remove damaged and normal mitochondria. The mitochondrial reactive oxygen species (ROS) scavenger Mito-TEMPO alleviated oxidative stress and mitochondrial autophagy levels, suggesting that mitochondrial ROS initiates this autophagic response. Notably, MMC activates mitochondrial autophagy via the monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signal pathway due to mitochondrial dysfunction. In vivo studies in mice revealed that MMC exposure decreased reproductive performance, attributed to excessive mitochondrial autophagy leading to reduced oocyte quality. Overall, these findings demonstrate that MMC exposure impairs oocyte maturation via the hyperactivation of mitochondrial autophagy induced by mitochondrial dysfunction.

The necroptosis of granulosa cells has been proven to be one of the important triggers of follicular atresia, which is an important cause of reduced reproductive capacity in cows. The rapid growth of granulosa cells is accompanied by endoplasmic reticulum stress (ERS), leading to granulosa cell death. However, the link between ERS and necroptosis, as well as its mechanism in bovine granulosa cells is still unclear. Itaconic acid is an endogenous anti-inflammatory and antioxidant small-molecule compound that can alleviate ERS. Therefore, the aim of the current study is to evaluate the effect of ERS on necroptosis and investigate the ameliorative effect of itaconic acid against ERS-induced necroptosis in granulosa cells. Bovine granulosa cells were treated with tunicamycin (Tm) to induce ERS. After the addition of the necroptosis inhibitor Nec-1 and the detection of the necroptosis inducer acetylcholinesterase (AChE), flow cytometry, transmission electron microscopy, and mass spectrometry were used to analyze the expression of itaconic acid and IRG1 in the granulosa cells. In addition, the role of the PERK pathway downstream of ERS in ERS-induced necroptosis was also investigated. We report here that ERS can induce necroptosis in granulosa cells. Itaconic acid supplementation significantly attenuates the effect of ERS-induced damage. In summary, this research provides a scientific basis and a drug reference for treating follicular atresia and improving bovine reproductive capacity.