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<p><i>BMPR1B</i> is considered to be the main effector gene affecting polytocous trait in sheep and other animals, and co-regulates reproductive performance with <i>BMP15</i>. Individuals containing the <i>BMPR1B</i> mutation had significantly higher lambing numbers than the wild type in Small-tailed Han sheep. However, the mode of regulation of <i>BMP15</i> in the three genotypes (<i>FecB</i> BB, <i>FecB</i> + + and <i>FecB</i> + B) of <i>BMPR1B</i> in the Small-tailed Han sheep remains unclear. To investigate the effect of <i>BMP15</i> on the proliferation of granulosa cells (GCs) from sheep with different <i>FecB</i> genotypes via the TGF-β/SMAD signaling pathway, we established an in vitro three-stage culture model (24h, 48h, 72h) using isolated GCs of three genotypes. We observed that <i>BMP15</i> promoted GCs proliferation across all genotypes, with proliferative activity increasing progressively over the culture period. This BMP15-mediated proliferative response was associated with the specific upregulation of key components within the TGF-β/SMAD pathway. Notably, the <i>FecB</i> BB genotype exhibited the highest proliferation efficiency. Furthermore, compared to the <i>FecB</i> + + and <i>FecB</i> + B genotypes, the <i>FecB</i> BB genotype displayed the highest mRNA and protein expression levels of both TGFβ receptor I (<i>TGFβ-R1</i>) and SMAD Family Member 4 (<i>SMAD4</i>). In summary, it was found that <i>BMP15</i> regulated GCs proliferation by affecting the expression of genes related to the TGF-β/SMAD signalling pathway. Compared with the <i>FecB</i> + + and <i>FecB</i> + B genotypes, the <i>FecB</i> BB genotype responded more strongly to BMP15 treatment, suggesting a genotype-dependent response. These results provided a basis for further investigation of the molecular mechanisms by which <i>BMP15</i> regulates GCs proliferation.</p>

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BMP15 regulates proliferation of sheep granulosa cells with different genotypes via the TGF-β/SMAD signaling pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月18日

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  • Qing Liu,
  • Guiling Cao,
  • Wentao Li,
  • Ziyi Liu,
  • Peng Wang,
  • Xiaoyun He,
  • Yufang Liu,
  • Mingxing Chu

摘要

BMPR1B is considered to be the main effector gene affecting polytocous trait in sheep and other animals, and co-regulates reproductive performance with BMP15. Individuals containing the BMPR1B mutation had significantly higher lambing numbers than the wild type in Small-tailed Han sheep. However, the mode of regulation of BMP15 in the three genotypes (FecB BB, FecB + + and FecB + B) of BMPR1B in the Small-tailed Han sheep remains unclear. To investigate the effect of BMP15 on the proliferation of granulosa cells (GCs) from sheep with different FecB genotypes via the TGF-β/SMAD signaling pathway, we established an in vitro three-stage culture model (24h, 48h, 72h) using isolated GCs of three genotypes. We observed that BMP15 promoted GCs proliferation across all genotypes, with proliferative activity increasing progressively over the culture period. This BMP15-mediated proliferative response was associated with the specific upregulation of key components within the TGF-β/SMAD pathway. Notably, the FecB BB genotype exhibited the highest proliferation efficiency. Furthermore, compared to the FecB + + and FecB + B genotypes, the FecB BB genotype displayed the highest mRNA and protein expression levels of both TGFβ receptor I (TGFβ-R1) and SMAD Family Member 4 (SMAD4). In summary, it was found that BMP15 regulated GCs proliferation by affecting the expression of genes related to the TGF-β/SMAD signalling pathway. Compared with the FecB + + and FecB + B genotypes, the FecB BB genotype responded more strongly to BMP15 treatment, suggesting a genotype-dependent response. These results provided a basis for further investigation of the molecular mechanisms by which BMP15 regulates GCs proliferation.