Rahman Md Ataur, Jalouli Maroua, Bhajan Sujay Kumar, Al-Zharani Mohammed, Harrath Abdel Halim
Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.
Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia.
Cells. 2025 Mar 14;14(6):437. doi: 10.3390/cells14060437.
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.
缺氧诱导因子-1α（HIF-1α）在卵巢癌进展中至关重要，尤其是在影响其肿瘤微环境以及促进使女性不孕症恶化的致病途径方面。在缺氧环境中，HIF-1α会被稳定下来，并激活与血管生成、代谢重编程、上皮-间质转化和治疗抗性相关的基因转录。HIF-1介导的血管生成和糖酵解重编程促进肿瘤增殖、存活和转移。其功能失调同时会损害卵巢内稳态，破坏卵泡生长、激素合成以及卵巢血管网络，从而导致不孕症。此外，HIF-1α会引发持续性炎症和氧化应激，促进对生殖健康有害的环境形成。由于其在卵巢癌生长和不孕症中的双重作用，HIF-1α是一个潜在的治疗靶点。包括小分子抑制剂和纳米颗粒介导的药物递送在内的策略具有降低HIF-1α活性的潜力，从而在保护生育能力的同时减少癌症进展。本综述旨在阐明HIF-1α在卵巢癌中的分子基础及其对女性不孕症的影响，为针对控制疾病和保护生育能力的新型治疗方法提供见解。
