VEZF1 Suppresses proliferation and induces premature luteinization of porcine granulosa cells

  • Theriogenology. 2026 Oct 1:263:118009. doi: 10.1016/j.theriogenology.2026.118009.
Jingxin Sun  1 ,  Jialong Li  1 ,  Yi Liu  1 ,  Luyao Wang  1 ,  Haifei Wang  2 ,  Shenglong Wu  2 ,  Wenbin Bao  2 ,  Aiwen Jiang  3
Affiliations
  • 1. Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, China.
  • 2. Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, China; Joint International Research Laboratory of Agriculture & Agri-Product Safety, Yangzhou University, Yangzhou, 225009, China.
  • 3. Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, China. Electronic address: [email protected].
PMID: 42202716 DOI: 10.1016/j.theriogenology.2026.118009
Abstract

Normal follicular development forms the foundation for female reproductive performance, a process critically supported by angiogenesis. However, vascular endothelial zinc finger 1 (VEZF1), a key transcription factor regulating angiogenesis, was unexpectedly found to negatively regulate the survival of porcine ovarian granulosa cells (GCs) in our previous study. This study aimed to further explore whether and how VEZF1 regulates porcine GC growth. Using cell cycle analysis, cell proliferation assays, and RNA-seq analysis, we found that VEZF1 expression was significantly downregulated during follicular development (p < 0.01). Overexpression of VEZF1 arrested the cell cycle at the G0/G1 phase, reduced the proportion of S-phase cells, and inhibited cell proliferation (p < 0.05), whereas knockdown of VEZF1 exerted the opposite effects. Overexpression of VEZF1 downregulated Cytochrome P450 family 19 subfamily A member 1 (CYP19A1), but upregulated Cytochrome P450 family 11 subfamily A member 1 (CYP11A1) and Steroidogenic acute regulatory protein (STAR) protein expression, accompanied by increased progesterone levels. Mechanistically, VEZF1 activated the cAMP/PKA signaling pathway through upregulating luteinizing hormone/choriogonadotropin receptor (LHCGR) and Adenylate Cyclase 8 (ADCY8). In summary, this study demonstrated that VEZF1 acts as a negative regulator of GC proliferation, and its overexpression induces premature luteinization of GCs accompanied by the loss of proliferative activity. These findings establish VEZF1 as a key regulator of follicular development and lay the foundation for further exploring the application of VEZF1 in regulating reproductive performance in sows.

Keywords
Angiogenesis; Granulosa cells; Luteinization; VEZF1; cAMP/PKA.
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