2. Academic Validation
  3. Semaphorin 4C regulates ovarian steroidogenesis through RHOA/ROCK1-mediated actin cytoskeleton rearrangement

Semaphorin 4C regulates ovarian steroidogenesis through RHOA/ROCK1-mediated actin cytoskeleton rearrangement

  • Mol Hum Reprod. 2023 Mar 9;gaad010. doi: 10.1093/molehr/gaad010.
Dan Chen 1 2 3,  Chuqing Wu 1 2 3,  Simin Wei 1 2 3,  Yican Guo 1 2 3,  Meng Wu 1 2 3,  Su Zhou 1 2 3,  Fangfang Fu 1 2 3,  Weicheng Tang 1 2 3,  Liru Xue 1 2 3,  Jinjin Zhang 1 2 3,  Yan Li 1 2 3,  Jun Dai 1 2 3,  Yuanyuan Li 1 2 3 4,  Shuangmei Ye 1 2 3,  Shixuan Wang 1 2 3
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
  • 2 National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, Hubei, 430030, China.
  • 3 Ministry of Education, Key Laboratory of Cancer Invasion and Metastasis, Wuhan, Hubei, 430030, China.
  • 4 Department of Gynecology, The Third Affiliated Hospital of Zhengzhou University, Henan International Joint Laboratory of Ovarian Malignancies, Zhengzhou, Henan, China.
PMID: 36892447 DOI: 10.1093/molehr/gaad010
Abstract

Semaphorins are a family of evolutionarily conserved morphogenetic molecules that were initially found to be associated with axonal guidance. Semaphorin 4C (Sema4C), a member of the fourth subfamily of semaphorins, has been demonstrated to play multifaceted and important roles in organ development, immune regulation, tumour growth and metastasis. However, it is completely unknown whether Sema4C is involved in the regulation of ovarian function. We found that Sema4C was widely expressed in the stroma, follicles and corpus luteum of mouse ovaries, and its expression was decreased at distinct foci in ovaries of mice of mid-to-advanced reproductive age. Inhibition of Sema4C by the ovarian intrabursal administration of recombinant adeno-associated virus (AAV)-shRNA significantly reduced oestradiol, progesterone and testosterone levels in vivo. Transcriptome Sequencing analysis showed changes in pathways related to ovarian steroidogenesis and the actin Cytoskeleton. Similarly, knockdown of Sema4C by siRNA interference in mouse primary ovarian granulosa cells (GCs) or thecal interstitial cells (TICs) significantly suppressed ovarian steroidogenesis and led to actin Cytoskeleton disorganization. Importantly, the cytoskeleton-related pathway RHOA/ROCK1 was simultaneously inhibited after downregulation of Sema4C. Furthermore, treatment with a ROCK1 agonist after siRNA interference stabilized the actin Cytoskeleton and reversed the inhibitory effect on steroid Hormones described above. In conclusion, Sema4C may play an important role in ovarian steroidogenesis through regulation of the actin Cytoskeleton via the RHOA/ROCK1 signalling pathway. These findings shed new LIGHT on the identification of dominant factors involved in the endocrine physiology of female reproduction.

Keywords

RHOA/ROCK1; Sema4C; Semaphorins; actin cytoskeleton; granulosa cells; ovarian steroidogenesis; thecal interstitial cells.

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