Journal of Clinical Medicine (Sep 2022)
Moderate Aerobic Exercise Regulates Follicular Dysfunction by Initiating Brain-Derived Neurotrophic Factor (BDNF)-Mediated Anti-Apoptotic Signaling Pathways in Polycystic Ovary Syndrome
Abstract
Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women. Moderate aerobic exercise intervention is considered an initial treatment strategy for managing PCOS. Brain-derived neurotrophic factor (BDNF) is an important molecular mediator and a beneficial response to exercise. We aimed to investigate the expression pattern and underlying molecular mechanisms of this neurotrophic factor during follicle development in ovarian tissues. The PCOS model was established by subcutaneous injection of 60 mg/kg dehydroepiandrosterone (DHEA) into the neck of Sprague Dawley rats for 35 consecutive days. PCOS rats then received aerobic exercise for 8 weeks. Body/ovarian weight and peripheral serum hormone levels were observed. Immunohistochemistry combined with Western blot analysis and fluorescence quantitative polymerase chain reaction were used to detect the changes in BDNF-TrkB/p75NTR pathway, apoptosis, and inflammatory factors. We show that moderate aerobic exercise not only reverses the PCOS phenotype but also activates the BDNF-TrkB pathway and initiates downstream targets. p-TrkB upregulates and phosphorylates phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) to inhibit apoptosis. In addition, aerobic exercise therapy reduces the high expression of p75NTR in the ovarian tissue of PCOS rats and initiates the anti-apoptotic effect from the downstream pathway of NF-κB/JNK. Our in vitro results state that treatment with BDNF ameliorated dihydrotestosterone (DHT)-induced granulosa cells (GCs) apoptosis by provoking p-TrkB activation and upregulating the PI3K/AKT pathway. The present study suggests that moderate aerobic exercise regulates follicular dysfunction in PCOS-like rats. One possible mechanism is to initiate the BDNF-mediated anti-apoptotic signaling pathway.
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