ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Reproduction
Ovarian Rev-erbα: A Central Regulator of Fertility Following Chrono-disruption
Provisionally accepted
Shalini Gupta1
Saumyata Kumawat2
Vipashu Kaushal2
Rashmi Arora2
Sumit Kumar3
Rahul Sharma2Anshu Bhardwaj2
NEERAJ KHATRI2
Pawan Gupta2*- 1Washington University in St Louis, St. Louis, United States
- 2Institute of Microbial Technology (CSIR), Chandigarh, India
- 3Cincinnati Children's Hospital Medical Center, Cincinnati, United States
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Circadian rhythm disruption in the form of shift work, nutritional imbalance, stress of modern lifestyle can affect hormone secretions, cause menstrual irregularities, impaired follicle development and ovarian hypoplasia. The mechanistic role of circadian rhythm disruption in the reproductive problems is not adequately studied. Nuclear receptors are known to play important role in female reproduction and in the maintenance of pregnancy. Rev-erbα, a circadian nuclear receptor is an important component of the circadian clock and maintains the circadian rhythm. We assessed the potential prophylactic and therapeutic function of Rev-erbα in upholding female fertility by orchestrating a sequence of events that culminate in successful pregnancy. We have generated a circadian rhythm disrupted female mice model for fertility study. Rev-erbα ligand SR9011 improves the fertility index of circadian rhythm disrupted female mice. Moreover, SR9011 treatment in circadian rhythm disrupted mice restores the impaired ovarian follicular cell proliferation and division, regulates steroidogenesis for steroid hormone production, improves progesterone and melatonin secretion, and ameliorates the adverse effects of circadian disruption on folliculogenesis. SR9011 attenuated circadian rhythm disrupted mice follicular atresia and helps in follicle development. Rev-erbα is a key regulator contributing to impaired oocyte retrieval, as observed in mice treated with the Rev-erbα antagonist SR8278. We conclude that Rev-erbα signaling and mechanistic role in the female reproduction could lead to more persuasive strategies for the treatment of female infertility. Rev-erbα is a sought-after druggable target, exhibiting a diverse range of potential therapeutic uses that has now drawn significant attention in the treatment of female infertility.
Keywords: Clock genes, folliculogenesis, REV-ERBα, Superovulation, therapeutic
Received: 10 Nov 2025; Accepted: 14 Jan 2026.
Copyright: © 2026 Gupta, Kumawat, Kaushal, Arora, Kumar, Sharma, Bhardwaj, KHATRI and Gupta. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Pawan Gupta
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