The Role of Hypoxia-Inducible Factor-1α (HIF-1α) in the Progression of Ovarian Cancer: Perspectives on Female Infertility.

PMID 40136686 | PMCID PMC11941611 | DOI 10.3390/cells14060437 · Cells · 2025

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Hypoxia-Inducible Factor-1α (HIF-1α) is crucial in the progression of ovarian cancer, especially in influencing its tumor microenvironment and promoting pathogenic pathways that worsen female infertility. In hypoxic settings, HIF-1α is stabilized and activates the transcription of genes associated with angiogenesis, metabolic reprogramming, epithelial-to-mesenchymal transition, and therapeutic resistance. Angiogenesis and glycolytic reprogramming mediated by HIF-1 tumor proliferation, survival, and metastasis. Its dysfunction concurrently impairs ovarian homeostasis, undermining follicular growth, hormone synthesis, and the ovarian vascular network, consequently contributing to infertility. Moreover, HIF-1α induces persistent inflammation and oxidative stress, promoting an environment damaging to reproductive health. Due to its dual function in ovarian cancer growth and infertility, HIF-1α is a potential therapeutic target. Strategies including small molecule inhibitors and nanoparticle-mediated delivery of drugs possess the potential to reduce HIF-1α activity, hence reducing cancer progression while protecting fertility. This review seeks to clarify the molecular basis of HIF-1α in ovarian cancer and its effects on female infertility, providing insights into novel treatment approaches that target both controlling the disease and preserving fertility.