Transforming growth factor-β1 disrupts angiogenesis during the follicular–luteal transition through the Smad–serpin family E member 1 (SERPINE1)/serpin family B member 5 (SERPINB5) signalling pathway in the cow

Intense angiogenesis is critical for the development of corpus luteum and tightly regulated by numerous factors. However, exact role transforming growth factor-β1 (TGFB1) plays during this follicular–luteal transition remains unclear. This study hypothesised that TGFB1, acting through TGFB receptor 1 (TGFBR1) Smad2/3 signalling, would suppress transition. Using a serum-free luteinising follicular culture system, TGFB1 (1 10 ng mL–1) markedly disrupted formation capillary-like structures, reducing endothelial cell network area number branch points (P < 0.001 compared with control). Furthermore, activated canonical Smad signalling inhibited nitric oxide synthase (NOS3) mRNA expression, but upregulated latent TGFB-binding protein TGFBR1, serpin family E member (SERPINE1) B 5 (SERPINB5) expression. SB431542, TGFBR1 inhibitor, reversed TGFB1-induced upregulation SERPINE1 SERPINB5. In addition, reduced progesterone synthesis decreasing expression steroidogenic acute regulatory (STAR), cytochrome P450 11 subfamily A (CYP11A1) 3β-hydroxysteroid dehydrogenase (HSD3B1) These results show regulates NOS3, SERPINB5 via could be mechanism which suppresses networks. Thereby, may provide homeostatic control The findings reveal molecular mechanisms underlying actions in early luteinisation, lead to novel therapeutic strategies reverse luteal inadequacy.