Relaxin regulation of endometrial structure and function in the rhesus monkey

Abstract

Despite the documented importance of the protein hormone relaxin in reproduction in various mammalian species, the role of relaxin in human reproduction is poorly understood, largely because of the lack of studies in women or in suitable non-human primate models. Here we describe the establishment of a non-human primate model of early human pregnancy and its use in defining the actions of relaxin. Results demonstrate that relaxin exerts dramatic uterine effects including pronounced increase in uterine weight and stimulation of endometrial angiogenesis and resident endometrial lymphocyte number. In addition, relaxin decreases endometrial levels of matrix metalloproteinases 1 and 3 and increases levels of their endogenous inhibitor, tissue inhibitor of metalloproteinase 1, resulting in maintenance of endometrial collagen content. Relaxin significantly inhibits endometrial levels of estrogen receptor alpha, but not beta, and of progesterone receptor isoforms A and B. The findings that relaxin stimulates new blood vessel formation and increases cytokine-containing lymphocyte number while maintaining endometrial connective tissue integrity are consistent with a significant role of relaxin in the establishment and/or maintenance of early pregnancy.

Fig. 1.

The effects of relaxin on monkey endometrial lymphocyte (A) and arteriole (B) number. Morphological assessments were performed as described in Materials and Methods. Each bar shows the mean value for one animal in either the control (open bar) or relaxin-treated (filled bar) group; at least five fields for each of at least three uterine sections per animal were assessed.

Fig. 2.

The effects of relaxin on monkey endometrial estrogen receptor α (Upper Left) and β (Upper Right) and progesterone receptor B (Lower Left) and A (Lower Right) expression. Western blot analyses were performed by using endometrial tissue from each monkey as described in Materials and Methods. Densitometric values from a representative blot are shown. Each bar shows the value for one animal in either the control (open bar) or relaxin-treated (filled bar) group.

Fig. 3.

The effects of relaxin on proMMP-1 (Upper Left), proMMP-3 (Upper Right), and TIMP-1 (Lower) expression. Data are expressed as in Fig. 2.