Follicle-stimulating hormone (FSH) coordinates ovarian follicle development by aligning mitochondrial biogenesis with increased metabolic demand. Although FSH is known to stimulate glycolysis in granulosa cells (GCs), the mechanism by which glycolytic flux coupled to mitochondrial biogenesis remains unclear. Here, we demonstrate that histone lactylation functions as a lactate-sensitive epigenetic mediator linking FSH-driven metabolic alterations to mitochondrial biogenesis in GCs. Mechanistically, FSH increases intracellular lactate levels through glycolytic activation, thereby promoting P300/CBP-dependent lactylation of histone H4 at lysine 5 (H4K5la). H4K5la directly enhances HDAC4 expression, and HDAC4 subsequently deacetylates PGC-1α at lysine residues 329/330. Deacetylated PGC-1α cooperates with nuclear respiratory factors NRF1/2 to drive transcription of key mitochondrial regulators (TFAM, TFB1M, TFB2M), ultimately promoting mitochondrial biogenesis. Disruption of the H4K5la/HDAC4/PGC-1α axis markedly impaired mitochondrial biogenesis and follicular development, evidenced by reduced ovarian weight, smaller follicle size, decreased antral follicle number, and impaired GC proliferation and estradiol (E2) production in FSH-treated mice. These findings identify a metabolic–epigenetic regulatory pathway in which histone lactylation links glycolysis to mitochondrial adaptation, providing mechanistic insight into FSH-dependent reproductive physiology.

Allele-specific expression (ASE) is a key regulatory mechanism linking genetic variation to phenotypic diversity. This study conducted a genome-wide ASE analysis in embryonic (brain, kidney, liver) and extraembryonic (chorion) tissues of Landrace × Meishan crossbred pigs. By integrating DNA sequencing of parental and F1 hybrids and RNA-sequencing of F1 tissues, a high-resolution ASE landscape was built via strict allele-specific SNP identification. Genomically, ASE genes (ASEG) were enriched on chromosomes 6, 7, 12, X and sparse on chromosome 11, and can be classified into extreme/moderate types by expression pattern and parental bias. Paternal ASEGs had higher expression levels, while maternal ones had higher abundance. Functionally, tissue-concordant ASEGs supported embryo/placenta basal development, tissue-specific ones matched organ core functions; maternal ASEGs were enriched in mitochondrial pathways, paternal ones in cell motility and RNA transcription. Besides, chorion had more allele-specific methylated regions than embryonic tissues, with opposite ASE directions. We proposed "orthogonal dual regulatory dimensions" for the relationship between ASE and tissue-specific expression. We also proposed regulatory models of extreme and moderate ASEGs, functional division modes between embryo and extraembryonic tissues, and between paternal and maternal alleles. This study clarifies tissue-specific ASE patterns and mechanisms, providing a framework for future ASE research.

Skeletal muscle differentiation relies on transient DNA strand breaks (DSBs), yet excessive DNA damage remains harmful to myogenic progression. The RNA-binding protein Zfp36l1 is expressed in skeletal muscle and contributes to muscle regeneration; nevertheless, its role in preserving genome stability during myogenic differentiation has not been defined. Here, we investigated the role and mechanism of Zfp36l1 in regulating DNA damage using C2C12 myoblast cells, combining loss- and gain-of-function assays, RNA-seq, and rescue experiments. The results revealed that Zfp36l1 expression is strongly induced during early myogenic differentiation, coinciding with the onset of physiological DSBs. Functional assays revealed that silencing Zfp36l1 aggravates DSB accumulation, reinforces G0/G1 cell cycle arrest, and promotes apoptosis, whereas Zfp36l1 overexpression attenuates these abnormalities. Transcriptomic profiling shows that Zfp36l1 knockdown impairs homologous recombination (HR)-mediated DNA repair by downregulating core repair factors, including Rad51 and Brca1. Gene set enrichment analysis further confirms significant suppression of the HR-dependent DSB repair pathway. Mechanistically, Zfp36l1 regulates HR repair by suppressing p21 expression, thereby relieving inhibition of E2F1-mediated Rad51 transcription. Co-silencing p21 restores Rad51 expression and reduces DNA damage in Zfp36l1-knockdown cells. Collectively, these findings identify Zfp36l1 as an essential safeguard of genome stability during myogenic differentiation by balancing DNA damage levels through the p21-E2F1-Rad51 signaling axis, and provide new insights into the regulatory basis of muscle development and genomic instability-associated muscle diseases.

Mitochondrial biogenesis is a fundamental process that ensures energy supply and supports steroidogenesis in ovarian cells. Lactate has recently been identified as a signaling metabolite that promotes mitochondrial biogenesis; however, the underlying regulatory mechanisms remain poorly defined. Here, we identify Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90α) lactylation as a key mediator that links glycolytic metabolism to mitochondrial function. Specifically, lactylation of HSP90α at K58 recruits ULK1, thereby enhancing phosphorylation at S39; lactylation at K616 prevents CDK5-mediated phosphorylation at S596. This dual regulation facilitates the nuclear translocation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and its isoform LRPGC1, which activate NRF1/2-dependent transcription of mitochondrial biogenesis genes, such as Tfb1m, Tfb2m, and Tfam. Functionally, mitochondrial mass expansion both enhances cellular energy metabolism and promotes cholesterol import into mitochondria, thereby driving estrogen biosynthesis. Together, these findings reveal a lactate-HSP90α-PGC1α/LRPGC1 axis that metabolically couples glycolysis to mitochondrial biogenesis and reproductive hormone production, providing insights into the epigenetic regulation of follicular development.

INTRODUCTION:Hypoxia, a condition characterized by inadequate oxygen supply to tissues, triggers various cellular responses, including apoptosis. The RNA demethylase FTO has been shown to exert anti-apoptotic effects, but its functions independent of RNA demethylase-particularly those involving protein-protein interactions-during hypoxia remain unclear. OBJECTIVES:This study aimed to elucidate the cytoprotective mechanism of FTO in preventing apoptosis under hypoxic stress. METHODS:NIH/3T3 cells, MEF cells, and mouse granulosa cells were cultured under hypoxia (1 % O2) and treated with inhibitors (chloroquine, MG132, cycloheximide) to identify FTO degradation pathways. RNA interference was used to knock down atg7, nedd4, and fto. Mass spectrometry identified FTO-associated proteins, and their interactions with FTO were analyzed with immunoprecipitation assays. FTO localization was examined through nuclear and cytoplasmic fractionation and fluorescence microscopy. Apoptosis was evaluated by flow cytometry (annexin V/PI). The role of FTO independent of its m6A demethylase activity was determined by inhibiting FTO function using FB23-2 or an H228A/D230A mutant lacking m6A demethylase activity. RESULTS:Upon hypoxia exposure, FTO relocated from the nucleus to the cytoplasm and underwent degradation through a regulatory pathway in which the E1-like ubiquitin-activating enzyme ATG7 and the E3 ubiquitin ligase NEDD4 cooperatively activated both the ubiquitin-proteasome system (UPS) and the autophagic-lysosomal pathway (ALP) in NIH/3T3 cells, MEF cells, and mouse granulosa cells. Furthermore, knocking down atg7 resulted in FTO accumulation in the cytoplasm, where FTO exerted its protective effect by binding with RACK1, which impairs the interaction between RACK1 and MTK1, thereby blocking activation of JNK1/2 and subsequently preventing apoptosis in hypoxic cells. CONCLUSION:This study reveals a novel function of cytoplasmic FTO in disrupting the RACK1-MTK1-JNK1/2-apoptosis cascade during hypoxia, positioning the functional context of FTO at the layer of protein-protein interactions, which extends its mechanistic role beyond RNA demethylation.

Background/Objectives: The avascular nature of the follicle creates a hypoxic microenvironment, establishing a niche where granulosa cells (GCs) rely on glycolysis to produce energy in the form of lactate (L-lactate). Autophagy, an evolutionarily conserved stress-response process, involves the formation of autophagosomes to encapsulate intracellular components, delivering them to lysosomes for degradation. This process plays a critical role in maintaining optimal follicular development. However, whether hypoxia regulates autophagy in GCs via lactate remains unclear. Methods: In this study, we investigated lactate-induced autophagy under hypoxia by utilizing glycolysis inhibitors or silencing related genes. Results: We observed a significant increase in autophagy in ovarian GCs under hypoxic conditions, indicated by elevated LC3II levels and reduced P62 levels. Suppressing lactate production through glycolytic inhibitors (2-DG and oxamate) or silencing lactate dehydrogenase (LDHA/LDHB) effectively reduced hypoxia-induced autophagy. Further investigation revealed that the HIF1-α/BNIP3/Beclin-1 axis is essential for lactate-induced autophagy under hypoxic conditions. Inhibiting HIF-1α activity using siRNAs or PX-478 downregulated BNIP3 expression and subsequently suppressed autophagy. Similarly, BNIP3 silencing with siRNAs repressed lactate-induced autophagy in hypoxic conditions. Mechanistically, immunoprecipitation experiments showed that BNIP3 disrupted pre-existing Bcl-2/Beclin-1 complexes by competing with Bcl-2 to form Bcl-2/BNIP3 complexes. This interaction released Beclin-1, which subsequently triggered lactate-induced autophagy under hypoxic conditions. Conclusions: These findings unveil a novel mechanism by which hypoxia regulates GC autophagy through lactate production, highlighting its potential role in sustaining follicular development under hypoxic conditions.

Body weight is an important trait associated with meat production in the poultry industry. To better understand the genetic basis of body weights in ducks, we estimated genetic parameters and performed a genome-wide association study. The phenotypic values of body weights at ages 0 weeks (bw0) and 8 weeks (bw8) were collected individually from 199 Loumen ducks, and their genotypes were assayed with whole genome re-sequencing. The heritability of bw0 and bw8 are 0.32 and 0.43, respectively, and the genetic correlation of bw0 and bw8 was very low (-7.256e-5). The genome-wide association study results identified eight SNPs significantly associated with bw0 and bw8. The two and nine genes nearest to the significant SNPs were selected as candidate genes: PIK3R5 and MYH10 for bw0, and LOC119717016, RHOJ, PPP2R5E, BRF1, LOC106018961, NUDT14, JAG2, CEP170B, and AKT1 for bw8. Together, the SNPs and candidate genes identified in this study advance understanding of the complex genetic architecture of bw0 and bw8, and provide important clues for future implementation of a genomic selection program in Loumen ducks.

Hypoxia-inducible factor 1α (HIF-1α) is a master regulator of cellular adaptation to hypoxia. Although prolyl hydroxylation-mediated degradation via the von Hippel–Lindau (VHL) ubiquitination complex is a well-established regulatory mechanism, the role of lactate-induced posttranslational modifications in HIF-1α stabilization remains incompletely understood. Here, we demonstrate that lactate induces lysine lactylation of HIF-1α at distinct residues across species—specifically, K644 in mice and K12 in humans and pigs—to increase protein stability by impairing VHL recognition. Mass spectrometry and mutagenesis analyses revealed that lactylation at these sites reduces K48-linked ubiquitination and proteasomal degradation, even when HIF-1α is hydroxylated. Structural modeling and functional assays revealed that lactylation sterically hinders VHL binding without affecting hydroxylation. Notably, lactylated HIF-1α exhibited increased transcriptional activity, as evidenced by increased promoter occupancy and upregulation of hypoxia-responsive genes (Vegfa, Glut1). Cross-species comparisons highlighted evolutionary divergence in lactylation sites while preserving the functional conservation of this modification. Our findings reveal that lactylation is a universal regulatory mechanism that overrides classical hydroxylation-dependent degradation, expanding our understanding of metabolic control over hypoxic signaling.

Sperm adhesion molecule 1(SPAM1) is a vital candidate gene that plays an important role in fertilization and hatchability of geese. In this study, we investigated for the first time the genetic variation of the SPAM1 gene and its association with egg production trait in Yangzhou geese. By using the direct sequencing technique, we detected three single nucleotide polymorphisms, g206 G>C, c123 T>A, and c159 T>C, located in the promoter and exon one regions, respectively. Six alleles and nine genotypes (GG, CC, GC, TT, TA, AA, TT, TC and CC) were obtained, respectively. The results indicated that the GG (g206 G>C) genotype had a significantly higher egg production rate during the 34-week egg-laying period. In the case of the SNPs c123 T > A and c159 T > C individuals with the AA and TT genotypes produced more eggs number, respectively. The SPAM 1 gene was highly expressed in the oviduct, abdominal fat, ovary and small intestine tissues. The mRNA expression level in the oviduct and ovary indicated that the geese with GG genotype recorded significantly lower expression levels (0.72 +/- 0.02; 0.93 +/- 0.02) compared to the geese with CC genotype (1.27 +/- 0.19, 1.11 +/- 0.06), respectively. Transcriptional activity results showed that both constructed vectors (pGL3-328G and pGL3-333C) had higher and more significant luciferase activity than the pGL3-basic vector. Future studies in Yangzhou and other native breeds of geese may be required to validate the association between these polymorphisms and egg production traits.

HMGB1, one of the most abundant nuclear non-histone proteins, also performs extracellular functions, and its nuclear export mechanisms have been extensively studied. Here, a novel mechanism of nuclear export for HMGB1 driven by lactylation is proposed. In addition, it is revealed that hypoxia-induced lactylation of HMGB1 facilitates its nuclear export in a complex with TIAR, promoting stress granule (SG) formation in the cytosol. Mass spectrometry revealed 12 lysine residues in HMGB1 undergoing lactylation, with K172 and K177 being the most susceptible. Functional studies using lysine-to-arginine mutants (K→R) demonstrated that lactylation at K177 is crucial for HMGB1-TIAR complex export, as K177R mutation completely blocked this export and subsequent SG formation. Notably, this lactylation-mediated mechanism is specific to hypoxic stress, while other stressors, such as sodium arsenite exposure and heat shock, triggered TIAR nuclear export and SG assembly independently of HMGB1. These findings reveal a previously unrecognized role of HMGB1 lactylation in mediating nuclear export and SG formation under hypoxia.

Mettl14, a key component of the m6A methyltransferase complex, plays a crucial role in regulating mRNA stability and splicing. Reduced expression of Mettl14 is associated with hepatocellular carcinoma and liver regeneration, yet the molecular mechanisms by which it regulates the hepatocyte cell cycle remain unclear. Using RNA-Seq and MeRIP-Seq in liver-specific Mettl14 knockout mice, we found that Mettl14 deficiency stabilizes Fam32a mRNA through m6A modifications, resulting in increased Fam32a protein levels. Elevated Fam32a expression accelerates the G1/S transition by modulating Cdkn1a splicing, specifically downregulating its variant 2. These findings uncover a novel m6A-dependent mechanism that regulates hepatocyte cell cycle progression and highlight the previously unrecognized role of Fam32a in promoting the G1/S transition.

Ovarian follicular development occurs under chronic hypoxia, imposing significant stress on granulosa cells (GCs) and leading to hypoxia-induced apoptosis, a key factor in follicular atresia and impaired fertility. However, the intrinsic mechanisms enabling GCs to resist hypoxic apoptosis remain unclear. Emerging evidence suggests lactate, beyond its traditional role as a glycolytic byproduct, functions as a critical mediator of cellular stress adaptation. Here, we investigated whether lactate confers protection to porcine granulosa cells (pGCs) by activating mitophagy under hypoxic conditions and elucidated the underlying molecular pathways. Using pGCs subjected to normoxia and hypoxia, combined with pharmacological inhibitors, RNA interference targeting LDHA, HIF-1α, and PINK1, mitochondrial membrane potential assays, apoptosis detection, Western blotting, and mitochondrial-lysosomal co-localization imaging, we demonstrated that lactate depletion exacerbates mitochondrial dysfunction and apoptosis under hypoxia. Conversely, exogenous lactate supplementation attenuated these effects by stabilizing HIF-1α and enhancing PINK1-Parkin-mediated mitophagy. Inhibition of mitophagy via 3-MA or PINK1 knockdown abolished lactate's protective effects, highlighting mitophagy as essential for lactate-mediated cell survival. Cross-species validation in murine granulosa cells (mGCs) in vitro and in vivo confirmed the conservation of lactate's protective mechanisms, where lactate depletion impaired mitochondrial function and increased follicular apoptosis, while lactate supplementation restored mitochondrial integrity and granulosa cell viability. Our findings reveal a novel lactate-HIF-1α-PINK1 signaling axis critical for pGCs resilience to hypoxic stress, offering new therapeutic targets for ovarian disorders such as polycystic ovary syndrome and ovarian aging.

Follicle-stimulating hormone (FSH) promotes follicular development by inducing the proliferation and differentiation of granulosa cells (GCs). This process is primarily attributed to the activation of the canonical G protein-coupled receptor (GPCR)/adenylyl cyclase/cAMP/PKA/CREB signaling pathway. Here, we revealed a novel mechanism wherein FSH promotes GCs proliferation and differentiation by stimulating cAMP response element-binding protein (CREB) lactylation. Specifically, FSH induced CREB lactylation at lysine 136 (K136la), leading to CREB phosphorylation at serine 133, which facilitated CREB/CBP/P300 complex formation for transcription activation. Moreover, K136la alone directly recruited CBP/P300, triggering transcriptional surges of proliferation and differentiation genes by binding with the cAMP response element (CRE), thereby stimulating GCs proliferation and differentiation. By contrast, a CREB mutation at K136 eliminated these effects. Blocking CREB lactylation using oxamate or C646 in vivo suppressed GCs proliferation, differentiation, and follicular development in mouse ovaries. These findings highlight the important role of lactylation between metabolic regulation and folliculogenesis, and its importance in mediating GPCR signaling, providing a theoretical basis for treating female infertility associated with defective follicular development.

This study established a method using ultra-performance liquid chromatography-tandem MS for the quantitative analysis of 9 harmful mycotoxins: zearalenone (ZEN), α-zearalanol, HT-2 toxin, T-2 toxin, ochratoxin A, fumonisin B1, deoxynivalenol, aflatoxin M1, and aflatoxin B1 in raw milk. The method exhibited good linearity, sensitivity, accuracy, and precision, making it suitable for trace analysis of these toxins in raw milk. We applied this method to analyze 200 raw milk samples from Heilongjiang Province, China, and found that they contained multiple mycotoxins, with a relatively high concentration of ZEN. To further explore the metabolism of these mycotoxins in dairy cows, we conducted a metabolic study on 12 lactating dairy cows. The results showed significant metabolic changes among the 9 mycotoxins, with ZEN demonstrating notably higher metabolic conversion rates compared with other mycotoxins in the transitions from feed to serum, from feed to milk, and from feed to feces. These findings provide new insights into the safety of raw milk and emphasize the importance of strict monitoring and regulation of these toxins in dairy products to protect human health. Simultaneously, we believe that future research should delve deeper into the metabolism of mycotoxins in dairy cows, which is crucial for ensuring public health safety.

It is known that asymmetrical maternal transcripts play an important role in the cell fate of the early embryo, but few studies are available in mammal oocytes especially in pig. To investigate the spatial factors in pig oocytes, the oriented bisection was established for collecting karyoplasts (NSOs) and cytoplasts (SSOs) with more than 95% efficiency. Subsequently, RNA-Seq and LC-MS/MS analysis were performed on NSOs and SSOs. Although no differentially expressed genes (DEGs) could be detected between NSOs and SSOs, 89 of the differentially expressed proteins (DEPs) were detected, that 58 proteins higher expressed but 31 proteins lower expressed in NSOs compared with SSOs. These DEPs mainly participated in the ‘cell cycle’ and ‘ribosome’ pathway, while the up-regulated DEPs were mainly GO in ‘spindle’ and ‘positive regulation of translation’, and the down-regulated DEPs were in ‘cytosolic small ribosomal subunit’ and ‘mRNA binding’. The up-regulated DEP SIRT5 which are related to the regulation of gene expression, epigenetic were further detected and revealed. A spatial asymmetry of maternal factors at the protein level was firstly detected in pig mature oocytes.

Extensive research has been conducted on the role of CXCR3 in immune responses and inflammation. However, the role of CXCR3 in the reproductive system, particularly in oocyte development, remains unknown. In this study, we present findings on the involvement of CXCR3 in the meiotic division process of mouse oocytes. We found CXCR3 was expressed consistently throughout the entire maturation process of mouse oocyte. Inhibition of CXCR3 impaired the asymmetric division of oocyte, while the injection of Cxcr3 mRNA was capable of restoring these defects. Further study showed that inhibition of CXCR3 perturbed spindle migration by affecting LIMK/cofilin pathway-mediated actin remodeling. Knockout of CXCR3 led to an upregulation of actin-binding protein and an increased ATP level in GV-stage oocytes, while maintaining normal actin dynamics during the process of meiosis. Additionally, we noticed the expression level of DYNLT1 is markedly elevated in CXCR3-null oocytes. DYNLT1 bound with the Arp2/3 complex, and knockdown of DYNLT1 in CXCR3-null oocytes impaired the organization of cytoplasmic actin, suggesting the regulatory role of DYNLT1 in actin organization, and the compensatory expression of DYNLT1 may contribute to maintain normal actin dynamics in CXCR3-knockout oocytes. In summary, our findings provide insights into the intricate network of actin dynamics associated with CXCR3 during oocyte meiosis.

Follicular fluid meiosis-activating sterol (FF-MAS) is a small molecule compound found in FF, named for its ability to induce oocyte resumption of meiosis. Granulosa cells (GCs) within the follicle are typically located in a hypoxic environment under physiologic conditions due to limited vascular distribution. Previous research suggests that hypoxia-induced cell cycle arrest and apoptosis in GCs may be crucial triggering factors in porcine follicular atresia. However, the impact of FF-MAS on GCs within follicles has not been explored so far. In this study, we uncovered a novel role of FF-MAS in facilitating GC survival under hypoxic conditions by inhibiting STAT4 expression. We found that STAT4 expression was upregulated in porcine GCs exposed to 1% O2. Both gain and loss of function assays confirmed that STAT4 was required for cell apoptosis under hypoxia conditions, and that the GC apoptosis caused by hypoxia was markedly attenuated following FF-MAS treatment through inhibition of STAT4 expression. Correlation analysis in vivo revealed that GC apoptosis was associated with increased STAT4 expression, while the FF-MAS content in follicular fluid was negatively correlated with STAT4 mRNA levels and cell apoptosis. These findings elucidate a novel role of FF-MAS-mediated protection of GCs by inhibiting STAT4 expression under hypoxia, which might contribute to the mechanistic understanding of follicular development.

Hypoxia that occurs during the luteinization process of granulosa cells (GC) contributes to the formation of lactate in follicles. Lysine lactylation (Kla), a post-translational modification directly regulated by lactate levels, is a metabolic sensor that converts metabolic information into gene expression patterns. In this study, we employed human chorionic gonadotropin (hCG) to induce GCs luteinization and discovered that hypoxia enhances hCG-mediated GCs luteinization by stimulating lactate production/lactylation. The elevated levels of luteinization markers (including progesterone synthesis, expression of CYP11A1 and STAR) were accompanied by increased lactate production as well as enhanced lactylation in mouse ovarian GCs after the injection of hCG in vivo. By treating GCs with hypoxia in vitro, we found that hypoxia accelerated hCG-induced GCs luteinization, which was inhibited after blocking lactate production/lactylation. Further investigations revealed that H3K18la might contribute to hCG-induced luteinization in hypoxic GCs by upregulating CYP11A1 and STAR transcription. Additionally, we identified that CREB K136la is also required for hCG-induced GCs luteinization under hypoxia. Finally, the in vitro findings were verified in vivo, which showed impaired GCs luteinization and corpus luteum formation after blocking the lactate/lactylation by intraperitoneal injection of oxamate/C646 in mice. Taken together, this study uncovered a novel role of protein lactylation in the regulation of GCs luteinization.

Follicle development, a crucial process in reproductive biology, hinges upon the dynamic proliferation of granulosa cells (GCs). Growth differentiation factor-8 (GDF8) is well-known as myostatin for inhibiting skeletal muscle growth, and it also exists in ovarian GCs and follicle fluid. However, the relationship between GCs proliferation and GDF8 remains elusive. Sulforaphane (SFN) is a potent bioactive compound, which in our study has been demonstrated to induce the expression of GDF8 in GCs. Meanwhile, we discover a novel role of SFN in promoting the proliferation of porcine GCs. Specifically, SFN enhances GCs proliferation by accelerating the progression of the cell cycle through the G1 phase to the S phase. By performing gene expression profiling, we showed that the promoting proliferative effects of SFN are highly correlated with the TGF-β signaling pathways and cell cycle. Among the ligand factors of TGF-β signaling, we identify GDF8 as a critical downstream effector of SFN, which acts through ALK5 to mediate SFN-induced proliferation and G1/S transition. In addition, we identify a noncanonical downstream pathway by which GDF8 induces the activation of MAPK/ERK to facilitate the cell cycle progression in GCs. Moreover, we reveal that the expression of GDF8 is regulated by SFN through epigenetic modifications of H3K27 acetylation. These findings not only provide mechanistic insights into the regulation of GCs proliferation but also establish a previously unrecognized role of GDF8 in follicle development, which have significant implications for developing strategies to improve female fertility.