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Many environmental and social factors have been reported to contribute to precocious puberty, such as early exposure to sexual content, influencing the timing of pubertal onset. However, the neuroendocrine regulatory mechanism behind this kind of stimulation has not been fully elucidated. In this study, immature female Sprague\u2013Dawley (SD) rats were subjected to odor and visual stimuli to mimic the girls\u2019 exposure to sex-related content, leading to an earlier onset of puberty. We further discovered a neural circuit between the amygdala and arcuate nucleus (ARC), where neurons, primarily from the medial amygdala (MeA), project to kisspeptin\/neurokinin B\/dynorphin (KNDy) neurons at ARC. Odor and visual temptation could activate acetylcholine neurons at the amygdala and then promote kisspeptin and GnRH expression in KNDy neurons at ARC. In turn, when the activity of VAChT or ChAT in MeA neurons was blocked, the stimulatory effect was subsequently weakened. Taken together, our study uncovers a novel modality of neural circuits to explain the molecular biology basis and effects of sexual content on central precocious puberty, and the potential pharmacological interventions may be considered as possible treatments and prevention.<\/jats:p>","DOI":"10.1021\/acsomega.5c01531","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T09:45:12Z","timestamp":1751967912000},"page":"30327-30334","source":"Crossref","is-referenced-by-count":1,"title":["Early Exposure\nof an Infantile Rat to Sex-Related\nContent Induces Precocious Puberty by Activation of Cholinergic Neurons\nin the Amygdala and KNDy Neurons in the Arcuate Nucleus"],"prefix":"10.1021","volume":"10","author":[{"given":"Yifen","family":"Shen","sequence":"first","affiliation":[{"name":"Soochow University , , , ,","place":["Suzhou, Jiangsu, China, 215200"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Yang","sequence":"additional","affiliation":[{"name":"Suzhou Ninth People\u2019s Hospital, Soochow University , , , ,","place":["Suzhou, Jiangsu, China, 215200"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, China, 200240"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Hu","sequence":"additional","affiliation":[{"name":"The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital , , , ,","place":["Zhengzhou, Henan, China, 450008"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Shen","sequence":"additional","affiliation":[{"name":"Soochow University , , , ,","place":["Suzhou, Jiangsu, China, 215200"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Li","sequence":"additional","affiliation":[{"name":"Suzhou Vocational Health College , , , ,","place":["Suzhou, Jiangsu, China, 215009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Soochow University , , , ,","place":["Suzhou, Jiangsu, China, 215006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Zhou","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, China, 200040"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2923-1641","authenticated-orcid":true,"given":"Yihang","family":"Shen","sequence":"additional","affiliation":[{"name":"Soochow University , , , ,","place":["Suzhou, Jiangsu, China, 215200"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"issue":"1","key":"2026081812224859400_cit1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000519039","article-title":"Genetic\nand Epigenetic Control of Puberty","volume":"16","author":"Manotas","year":"2022","journal-title":"Sexual development:\ngenetics, molecular biology, evolution, endocrinology, embryology,\nand pathology of sex determination and differentiation"},{"key":"2026081812224859400_cit2","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.omtn.2021.05.014","article-title":"The epigenetic\nrole of HTR1A antagonist in facilitaing GnRH expression for pubertal\ninitiation control","volume":"25","author":"Zhou","year":"2021","journal-title":"Molecular therapy. 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