DHEA promotes ovarian angiogenesis and improves ovarian function in POI rats by up-regulating HIF-1α/VEGF signalling

Abstract

Research QuestionDehydroepiandrosterone (DHEA) promotes tissue function recovery in different diseases by stimulating angiogenesis; however, its impact on ovarian angiogenesis and function in rats with premature ovarian insufficiency (POI) and the potential mechanisms of action remain uncertain. DesignDHEA was co-cultured with human microvascular endothelial cells (HMEC-1) cells to investigate its effects on cell proliferation, migration, and tube formation. A rat model of POI was established by intraperitoneal injection of cyclophosphamide (CTX), followed by continuous oral administration of DHEA for 28 d. Ovarian angiogenesis, follicular growth, and granulosa cell (GC) survival in ovarian tissues were assessed through haematoxylin-eosin staining, immunohistochemistry, and TUNEL. The effect of DHEA on the fertility of rats with POI was evaluated in pregnant animals. The expression levels of characteristic genes and proteins in the hypoxia-inducible factor (HIF)-1α/vascular endothelial growth factor (VEGF) pathway was determined using quantitative reverse transcription-PCR and western blotting. ResultsIn vitro experiments revealed that DHEA stimulated the proliferation, migration, and tube formation of HMEC-1 cells. In in vivo studies, DHEA treatment improved the disruption of estrous cycle and hormone imbalances in POI rats. Key genes in the HIF-1α/VEGF pathway exhibited upregulated expression, promoting ovarian angiogenesis in POI rats, and enhancing follicular development and GC survival, thereby restoring fertility in rats. ConclusionsDHEA can potentially restore ovarian function in CTX-induced POI rats by upregulating HIF-1α/VEGF signalling, which promotes the growth of blood vessels in the ovaries.