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Updated: May 26, 2026

Z-Scores for Assessing Ovarian Reserve in Young Patients Undergoing Fertility Preservation
Published on: October 25, 2024
Brain Serotonin Deficiency Impairs Ovarian Reserve Function via the Hypothalamic-Pituitary-Ovarian Axis
Shuang-Shuang Cui1,2, Zhuo-Nan Yang1,2, Jin Xiao3
1Department of Obstetrics and Gynecology, NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
None:
Brain-derived serotonin (5-HT) is a key neurotransmitter that regulates diverse central and peripheral physiological processes, including endocrine function, mood, and circadian rhythms. Patients with anxiety and depression often exhibit reduced brain 5-HT levels, which contribute significantly to female infertility. However, the role of brain-derived 5-HT in maintaining ovarian reserve function remains unclear. We generated brain-specific Tph2 conditional knockout (Tph2-CKO) mice lacking 5-HT and observed reduced follicle numbers and anti-Müllerian hormone (AMH) levels, indicating diminished ovarian reserve (DOR). Mechanistically, Brain-derived 5-HT deficiency suppressed ovarian mTOR signaling, triggering excessive autophagy, mitochondrial dysfunction, and apoptosis. In the hypothalamus, reduced central 5-HT levels downregulated 5-HT receptor 7 (HTR7)-cAMP/PKA signaling, disrupted circadian rhythms, and decreased gonadotropin-releasing hormone (GnRH) expression, impairing hypothalamic-pituitary-ovarian (HPO) axis function. Ovarian follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) levels decreased, ultimately leading to DOR. Thus, 5-HT deficiency in the dorsal raphe nucleus disrupts the HPO axis via HTR7, leading to DOR.
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