The FSH-mTOR-CNP signaling axis initiates follicular antrum formation by regulating tight junction, ion pumps, and aquaporins

  • J Biol Chem. 2023 Jul 4;105015. doi: 10.1016/j.jbc.2023.105015.
Xiaodong Wang  1 ,  Shanshan Zhou  1 ,  Zian Wu  1 ,  Ruiyan Liu  1 ,  Zaohong Ran  1 ,  Jianning Liao  1 ,  Hongru Shi  1 ,  Feng Wang  2 ,  Jianguo Chen  1 ,  Guoshi Liu  3 ,  Aixin Liang  1 ,  Liguo Yang  1 ,  Shujun Zhang  1 ,  Xiang Li  1 ,  Changjiu He  4
Affiliations
  • 1. National Center for International Research on Animal Genetics, Breeding and Reproduction / Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Sciences and Technology / Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.
  • 2. Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, USA.
  • 3. Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, China.
  • 4. National Center for International Research on Animal Genetics, Breeding and Reproduction / Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Sciences and Technology / Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China. Electronic address: [email protected].
PMID: 37414146 DOI: 10.1016/j.jbc.2023.105015
Abstract

The initial formation of the follicular antrum (iFFA) serves as a dividing line between gonadotropin-independent and gonadotropin-dependent folliculogenesis, enabling the follicle to sensitively respond to gonadotropins for its further development. However, the mechanism underlying iFFA remains elusive. Herein, we reported that iFFA is characterized by enhanced fluid absorption, energy consumption, secretion, and proliferation, and shares a regulatory mechanism with blastula cavity formation. By use of bioinformatics analysis, follicular culture, RNA interference, and Other techniques, we further demonstrated that the tight junction, ion pumps, and aquaporins are essential for follicular fluid accumulation during iFFA, as a deficiency of any one of these negatively impacts fluid accumulation and antrum formation. The intra-ovarian mTOR-CNP pathway, activated by FSH, initiated iFFA by activating tight junction, ion pumps, and aquaporins. Building on this, we promoted iFFA by transiently activating mTOR in cultured follicles and significantly increased oocyte yield. These findings represent a significant advancement in iFFA research, further enhancing our understanding of folliculogenesis in mammals.

Keywords
CNP; FSH; aquaporin; follicle; follicular antrum; ion pump; mTOR; tight junction.
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