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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

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 Thumbnail


Authors

Leyan Yan

Xiaolu Qu

Jianning Yu

KATIE WOAD katie.woad@nottingham.ac.uk
Assistant Professor

Zhendan Shi



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

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