Decoding implantation and menstruation: the tale of two opposing signals

Human endometrium is a unique tissue that undergoes sequential phases of proliferation, and secretory changes followed by tissue shedding and bleeding during menstruation. Tissue remodeling is a distinct feature of human endometrium in the secretory phase which prepares endometrium for implantation during the "receptive phase" of the cycle. A discrete dissolution of extracellular matrix (ECM) by a host of enzymes called matrix metalloproteases (MMP) is required for a successful implantation. In the absence of implantation, as a result of progesterone withdrawal, human endometrium loses its receptive state in the premenstrual period and subsequently undergoes a generalized breakdown of ECM by MMPs during menstruation. The homeostasis of ECM of endometrium and the delicate balance between its synthesis and degradation appear to be mediated by reciprocal interaction between TGF-beta and ebaf (lefty) signaling. While TGF-beta acts as a pro-fibrogenic cytokine and maintains the integrity of ECM in endometrium, expression of lefty is associated with events that lead to destruction of ECM facilitating tissue shedding.