Hypoxia and the endometrium: An indispensable role for HIF-1α as therapeutic strategies

Hypoxia-inducible factor 1 alpha (HIF-1 alpha) is a major molecular mediator of the hypoxic response. In the endometrium, local hypoxic conditions induced by hormonal fluctuations and endometrial vascular remodeling contribute to the production of HIF-1 alpha, which plays an indispensable role in a series of physiological activities, such as menstruation and metamorphosis. The sensitive regulation of HIF-1 alpha maintains the cellular viability and regenerative capacity of the endometrium against cellular stresses induced by hypoxia and excess reactive oxygen species. In contrast, abnormal HIF-1 alpha levels exacerbate the development of various endometrial pathologies. This knowledge opens important possibilities for the development of promising HIF-1 alpha-centered strategies to ameliorate endometrial disease. Nonetheless, additional efforts are required to elucidate the regulatory network of endometrial HIF-1 alpha and promote the applications of HIF-1 alpha-centered strategies in the human endometrium. Here, we summarize the role of the HIF-1 alpha-mediated pathway in endometrial physiology and pathology, highlight the latest HIF-1 alpha-centered strategies for treating endometrial diseases, and improve endometrial receptivity.