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However, its precise physiological mechanisms remain largely elusive. In this study, using a mouse model of SD, it is demonstrated that SD induces the depletion of ovarian primordial follicles, a phenomenon not attributed to immune\u2010mediated attacks or sympathetic nervous system activation. Rather, the excessive secretion of stress hormones, namely norepinephrine (NE) and epinephrine (E), by overactive adrenal glands, has emerged as a key mediator. The communication pathway mediated by the KIT ligand (KITL)\u2010KIT between granulosa cells and oocytes plays a pivotal role in primordial follicle activation. SD heightened the levels of NE\/E that stimulates the activation of the KITL\u2010KIT\/PI3K and mTOR signaling cascade in an \u03b22 adrenergic receptor (ADRB2)\u2010dependent manner, thereby promoting primordial follicle activation and consequent primordial follicle loss in vivo. In vitro experiments further corroborate these observations, revealing that ADRB2 upregulates KITL expression in granulosa cells via the activation of the downstream cAMP\/PKA pathway. Together, these results reveal the significant involvement of ADRB2 signaling in the depletion of ovarian primordial follicles under sleep\u2010deprived conditions. Additionally, ADRB2 antagonists are proposed for the treatment or prevention of excessive activation of primordial follicles induced by SD.<\/jats:p>","DOI":"10.1002\/advs.202402393","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T07:25:20Z","timestamp":1725434720000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Sleep Deprivation Triggers the Excessive Activation of Ovarian Primordial Follicles via \u03b22 Adrenergic Receptor Signaling"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3414-1688","authenticated-orcid":false,"given":"Lichun","family":"Weng","sequence":"first","affiliation":[{"name":"The International Peace Maternity and Child Health Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200030 China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases  Shanghai 200030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanqing","family":"Hong","sequence":"additional","affiliation":[{"name":"The International Peace Maternity and Child Health Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200030 China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases  Shanghai 200030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"The International Peace Maternity and Child Health Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200030 China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases  Shanghai 200030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengqi","family":"Xiao","sequence":"additional","affiliation":[{"name":"The International Peace Maternity and Child Health Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200030 China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases  Shanghai 200030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuwan","family":"Zhang","sequence":"additional","affiliation":[{"name":"The International Peace Maternity and Child Health Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200030 China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases  Shanghai 200030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"The International Peace Maternity and Child Health Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200030 China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases  Shanghai 200030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju","family":"Huang","sequence":"additional","affiliation":[{"name":"Songjiang Hospital and Songjiang Research Institute Shanghai Key Laboratory of Emotions and Affective Disorders Shanghai Jiao Tong University School of Medicine  Shanghai 201600 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3810-2136","authenticated-orcid":false,"given":"Dongmei","family":"Lai","sequence":"additional","affiliation":[{"name":"The International Peace Maternity and Child Health Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200030 China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases  Shanghai 200030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,4]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202591"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2020.08.1429"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-021-02260-8"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2012.11.037"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/aogs.14008"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2023.02.014"},{"key":"e_1_2_9_6_1","volume":"2010","author":"Ari S.","year":"2010","journal-title":"Int. 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