Hypoxia-inducible factors (HIFs) in early pregnancy: implications for miscarriage†

Miscarriage poses a significant threat to both maternal and fetal health. Its etiology remains unknown, and there are no established effective identification or prevention strategies. A low-oxygen environment in early pregnancy is a physiological necessity for embryonic and placental growth. Hypoxia-inducible factors are a family of classic hypoxia signaling molecules whose expression level may fluctuate abnormally because of an imbalance in oxygen levels. Its unusual fluctuations initiate multiple signaling pathways at the maternal womb. Hypoxia-inducible factors are a family of classic hypoxia-signaling molecules and immune tolerance. Notably, aberrant regulation of these processes may lead to miscarriage. This review aims to clarify how the hypoxia-inducible factor-1α mediates the aberrant regulation of biological processes, including autophagy, metabolic reprogramming, et al., and how these effects impact trophoblasts and other cells at the maternal-fetal interface. These findings provide new insights into potential therapeutic and preventive strategies for miscarriage.