1. Academic Validation
  2. SRA deficiency induces follicular dysplasia by disrupting the hypothalamic Kisspeptin-GPR54 system in mice

SRA deficiency induces follicular dysplasia by disrupting the hypothalamic Kisspeptin-GPR54 system in mice

  • Biol Reprod. 2025 Mar 9:ioaf049. doi: 10.1093/biolre/ioaf049.
Jing Jin 1 Xinhui Kou 2 Xinzhe Wang 1 Xue Yun 3 Yinyin Ding 1 Keshu Cai 4 Yongning Zhai 3 5 Huifang Zhou 1
Affiliations

Affiliations

  • 1 Department of Gynecology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, China.
  • 2 Department of Pharmacy, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518033, China.
  • 3 Department of Gynecology, Nanjing Lishui District Maternity and Child Health Care Hospital, Nanjing 211299, China.
  • 4 Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
  • 5 Department of Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing 210004, China.
Abstract

Purpose: To investigate how steroid receptor RNA activator (SRA) regulates follicular development in mice.

Methods: Systemic SRA knockout mice were introduced. SRA expression was reinstated in the anteroventral periventricular nucleus (AVPV) of the hypothalamus using lentiviral vectors. Subsequently, the estrous cycle, serum hormone levels, follicle development, and hypothalamic kisspeptin expression in mice were assessed. Kiss1 promoter activity was tested with a fluorescent reporter system in Neuro-2a cells.

Results: SRA deficiency caused a shift to shorter metestrus and longer diestrus phases, reduced numbers of large antral and preovulatory follicles, increased formation of atretic cyst-like follicles, lowered serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2), and decreased expression of hypothalamic AVPV-kisspeptin in mice. The reinstatement of SRA expression in the AVPV nucleus normalized kisspeptin expression, hormone levels, and follicle development. In Neuro-2a cells, SRA increased Kiss1 transcription upon E2 treatment, a response that was nullified by the Estrogen Receptor alpha (ERα) inhibitor.

Conclusion: SRA enhances ERα-mediated Kiss1 transcription in the AVPV nucleus to control the kisspeptin-GPR54 system in hypothalamus, essential for regulating ovulation through the hypothalamus-pituitary-ovary axis.

Keywords

Follicular dysplasia; Hypothalamus; Kisspeptin; Sra.

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