Relaxin regulates endometrial structure and function in the rhesus monkey

The actions of relaxin are highly species specific. The role of relaxin in human endometrial function has not been well understood because of the paucity of in vivo studies in women or in suitable primate models. A model of early human pregnancy was established in ovariectomized, steroid-primed rhesus monkeys. Relaxin exerts dramatic uterine effects in this model, including a pronounced increase in uterine weight and stimulation of endometrial angiogenesis. In addition, relaxin negatively regulates expression of endometrial matrix metalloproteinases (MMP), causing decreased endometrial levels of MMP-1 and MMP-3 proteins and increased protein levels of their endogenous inhibitor, tissue inhibitor of metalloproteinase 1. This results in maintenance of endometrial collagen content. The negative effects of relaxin on MMP expression in the endometrium are in distinct contrast to the positive regulation of MMPs previously shown in fibroblasts from other tissues including the cervix. Relaxin also significantly inhibits endometrial levels of estrogen receptor alpha and significantly inhibits levels of progesterone isoforms B and A. The findings that relaxin stimulates new blood vessel formation while maintaining endometrial connective tissue integrity are consistent with a significant role of relaxin in the establishment and/or maintenance of early pregnancy.