ERβ Regulation of Indian Hedgehog Expression in the First Wave of Ovarian Follicles

• Published in: Cells (Basel, Switzerland) Switzerland), 2024-04, Vol.13 (7), p.644
• Main Authors: Chakravarthi, V Praveen, Dilower, Iman, Ghosh, Subhra, Borosha, Shaon, Mohamadi, Ryan, Dahiya, Vinesh, Vo, Kevin, Lee, Eun B, Ratri, Anamika, Kumar, Vishnu, Marsh, Courtney A, Fields, Patrick E, Rumi, M A Karim
• Format: Article
• Language: English
• Subjects: Bioinformatics; Cellular signal transduction; Down-regulation; Estrogen; estrogen receptor β; Estrogens; Follicles; Gene expression; Genetic aspects; Genomics; Granulosa cells; Hedgehog protein; Hedgehog proteins; Hybridization; Indian hedgehog; Kinases; Obstetrical research; ovarian development; Ovaries; Ovulation; Physiological aspects; primordial follicle activation; Receptors; the first wave of ovarian follicles; transcriptome analysis; Transcriptomes
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells13070644

Increased activation of ovarian primordial follicles in knockout ( ) rats becomes evident as early as postnatal day 8.5. To identify the ERβ-regulated genes that may control ovarian primordial follicle activation, we analyzed the transcriptome profiles of rat ovaries collected on postnatal days 4.5, 6.5, and 8.5. Compared to wildtype ovaries, ovaries displayed dramatic downregulation of Indian hedgehog ( ) expression. IHH-regulated genes, including , and were also downregulated in ovaries. This was associated with a downregulation of steroidogenic enzymes , , and . The expression of remained very low in ovaries despite the high levels of and , which are known upregulators of expression in the granulosa cells of activated ovarian follicles. Strikingly, the downregulation of the gene in ovaries began to disappear on postnatal day 16.5 and recovered on postnatal day 21.5. In rat ovaries, the first wave of primordial follicles is rapidly activated after their formation, whereas the second wave of primordial follicles remains dormant in the ovarian cortex and slowly starts activating after postnatal day 12.5. We localized the expression of mRNA in postnatal day 8.5 wildtype rat ovaries but not in the age-matched ovaries. In postnatal day 21.5 rat ovaries, we detected mRNA mainly in the activated follicles in the ovaries' peripheral regions. Our findings indicate that the expression of in the granulosa cells of the activated first wave of ovarian follicles depends on ERβ.