Relaxin Regulation of Endometrial Structure and Function in the Rhesus Monkey

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 101; no. 13; pp. 4685 - 4689
• Main Authors: Goldsmith, Laura T., Weiss, Gerson, Palejwala, Smita, Plant, Tony M., Wojtczuk, Andrea, Lambert, W. Clark, Ammur, Nael, Heller, Debra, Skurnick, Joan H., Edwards, Dean, Cole, Donna M., Lieberman, Seymour
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 30.03.2004; National Acad Sciences
• Subjects: Anatomy & physiology; Animals; Biological Sciences; Body Weight; Connective tissues; Endocrinology; Endometrium; Endometrium - anatomy & histology; Endometrium - blood supply; Endometrium - physiology; Epithelial cells; Estradiol - pharmacology; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogen receptors; Female; Hormones; Humans; Lymphocytes; Macaca mulatta; Mammals; Monkeys & apes; Neovascularization, Physiologic - drug effects; Organ Size - drug effects; Ovariectomy; Pregnancy; Primates; Progesterone - pharmacology; Progesterone receptors; Proteins; Receptors, Estrogen - antagonists & inhibitors; Receptors, Estrogen - drug effects; Receptors, Estrogen - physiology; Relaxin - physiology; Reproduction; Uterus - anatomy & histology; Uterus - drug effects
• DOI: 10.1073/pnas.0400776101
• ISSN: 0027-8424

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 α, but not β, 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.