Hypoxia: involved but not essential for endometrial breakdown in mouse menstural-like model

Abstract

Menstruation is a specific physiological phenomenon that occurs in women. However, molecular mechanisms underlying this phenomenon are still unclear. According to the classical theory, tissue hypoxia resulting from vasoconstriction of the spiral arteries after progesterone (P4) withdrawal initiates the breakdown of the endometrium at the earliest stage of menstruation. However, this theory has been challenged by previous studies that have questioned the function and even the existence of hypoxia during menstruation. In this study, we not only provide convincing evidence that hypoxia exists during endometrial breakdown, but also further explore the role of hypoxia and hypoxia-inducible factor 1 (HIF1) in this process. Based on mouse menstrual-like model and experiments with human decidual stromal cells, we observed that P4 withdrawal induced both hypoxia and HIF1 activation; however, endometrial breakdown was triggered only by P4 withdrawal. Hypoxia significantly enhanced the mRNA expression of specific matrix metalloproteinases (MMPs) under the conditions of P4 withdrawal. In conclusion, hypoxia is involved but not an essential component of endometrial breakdown during menstruation.