{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:33:06Z","timestamp":1787027586918,"version":"build-2736575974"},"reference-count":30,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Major Science and Technology Projects of Yunnan Province","award":["202502AE090026"],"award-info":[{"award-number":["202502AE090026"]}]},{"name":"Major Science and Technology Projects of Yunnan Province","award":["202202AE090005"],"award-info":[{"award-number":["202202AE090005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Broodiness in poultry represents a major bottleneck for reproductive performance, governed by complex remodeling of the hypothalamic-pituitary-ovarian (HPO) axis. CYP11A1, the rate-limiting enzyme in steroidogenesis, is essential for hormone synthesis; however, its spatiotemporal dynamics within the HPO axis during reproductive transitions remain unclear. Using the Wuding chicken as a model, this study characterized the expression profile and cellular function of CYP11A1. We identified a distinct \u201covary-hypothalamus expression inversion\u201d pattern: CYP11A1 expression exhibited an ovary-dominant pattern during the egg-laying period to support folliculogenesis; however, this shifted to a hypothalamus-dominant pattern during the broodiness period. This inversion indicates its active role in central neurosteroid modulation rather than a passive response to HPO axis regression. In vitro assays in granulosa cells (GCs) demonstrated that CYP11A1 overexpression significantly upregulated AKT1 and mTOR transcription, promoted the G0\/G1 to S\/G2\/M cell cycle transition, and enhanced cell proliferation. Conversely, CYP11A1 knockdown arrested the cell cycle and suppressed the PI3K\/AKT\/mTOR pathway. Additionally, CYP11A1 coordinated the expression of steroidogenic genes (STAR, HSD3B1), reflecting a coupling between steroid metabolism and cell growth. These findings reveal CYP11A1 as a critical molecular node linking HPO axis remodeling, granulosa cell proliferation, and steroidogenesis, providing a potential target for molecular breeding to mitigate broodiness in indigenous chickens.<\/jats:p>","DOI":"10.3390\/ani16040657","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T08:51:09Z","timestamp":1771491069000},"page":"657","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatiotemporal Expression Inversion of CYP11A1 in the HPO Axis and Its Regulation of Granulosa Cell Proliferation via the PI3K\/AKT\/mTOR Pathway in Wuding Chickens"],"prefix":"10.3390","volume":"16","author":[{"given":"Enmin","family":"Wan","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Yunnan Agricultural University, Kunming 650201, China"},{"name":"Animal Genetics and Breeding Institute, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yunnan Agricultural University, Kunming 650201, China"},{"name":"Animal Genetics and Breeding Institute, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cailing","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yunnan Agricultural University, Kunming 650201, China"},{"name":"Animal Genetics and Breeding Institute, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinda","family":"Li","sequence":"additional","affiliation":[{"name":"Institutional Center for Shared Technologies and Facilities of Kunming Institute of Zoology (KIZ), Chinese Academy of Sciences (CAS), Kunming 650223, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyang","family":"Fan","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yunnan Agricultural University, Kunming 650201, China"},{"name":"Animal Genetics and Breeding Institute, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2127-0379","authenticated-orcid":false,"given":"Yongwang","family":"Miao","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yunnan Agricultural University, Kunming 650201, China"},{"name":"Animal Genetics and Breeding Institute, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hanlon, C., Takeshima, K., and B\u00e9d\u00e9carrats, G.Y. 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