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

Yan, Leyan; Qu, Xiaolu; Yu, Jianning; Robinson, Bob; Woad, Kathryn; Shi, Zhendan

Abstract

Intense angiogenesis is critical for the development of the corpus luteum and is tightly regulated by numerous factors. However, the exact role transforming growth factor beta 1 (TGFB1) plays during this follicular-luteal transition remains unclear. This study hypothesized that TGFB1 acting through TGFBR1 and Smad2/3 signaling would suppress angiogenesis during the follicular-luteal transition. Using a serum-free luteinizing follicular angiogenesis culture system, TGFB1 (1 and 10ng.mL-1) markedly disrupted the formation of capillary-like structures, reducing endothelial cell network area and number of branch points (P[less than]0.001). Furthermore, TGFB1 activated canonical Smad signaling and inhibited endothelial nitric oxide synthase (NOS3) mRNA expression, but up-regulated latent TGF-beta binding protein, type I TGFB receptor (TGFBR1), SERPINE1 and SERPINB5 mRNA expression. TGFBR1 inhibitor, SB431542, reversed the SERPINE1 and SERPINB5 up-regulation by TGFB1. Additionally, TGFB1 reduced progesterone synthesis through decreasing STAR, CYP11A1 and HSD3B1 expression. These results show that TGFB1 regulated NOS3, SERPINE1, and SERPINB5 expression via TGFBR1 and Smad2/3 signaling and could be the mechanism by which TGFB1 suppresses endothelial networks. Thereby, TGFB1 may provide a critical homeostatic control of angiogenesis during the follicular-luteal transition. Our findings reveal the molecular mechanisms underlying the actions of TGFB1 in early luteinization which may lead to novel therapeutic strategies to reverse luteal inadequacy.

Citation

Yan, L., Qu, X., Yu, J., Robinson, B., Woad, K., & Shi, Z. (2021). 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. Reproduction, Fertility and Development, 33(10), 643-654. https://doi.org/10.1071/RD20325

• Journal Article Type: Article
• Acceptance Date: Apr 13, 2021
• Online Publication Date: May 19, 2021
• Publication Date: May 19, 2021
• Deposit Date: Apr 29, 2021
• Publicly Available Date: May 19, 2021
• Journal: Reproduction, Fertility and Development
• Print ISSN: 1031-3613
• Electronic ISSN: 1448-5990
• Publisher: CSIRO Publishing
• Peer Reviewed: Peer Reviewed
• Volume: 33
• Issue: 10
• Pages: 643-654
• DOI: https://doi.org/10.1071/RD20325
• Public URL: https://nottingham-repository.worktribe.com/output/5502675
• Publisher URL: https://www.publish.csiro.au/RD/RD20325
• Related Public URLs: https://www-publish-csiro-au.ezproxy.nottingham.ac.uk/RD/justaccepted/RD20325