The Role of Relaxin in Normal and Abnormal Uterine Function During the Menstrual Cycle and Early Pregnancy

The hormone relaxin is a 6-kDa peptide with high structural similarity to insulin. It is primarily produced by the corpus luteum during pregnancy but is also synthesized by other reproductive organs such as the uterus, decidua, and placenta. Relaxin binds to its receptor RXFP1, which has been localized to a wide variety of reproductive and nonreproductive tissues. The peptide's many uterotropic effects include stimulating uterine growth and vascularization, remodeling extracellular matrix components, and regulating vascular endothelial growth factor in preparation for implantation. Evidence also supports a role for relaxin in the systemic maternal vascular adaptations required for a healthy pregnancy. Diminished relaxin levels in early pregnancy are linked with increased risks of miscarriage and the development of preeclampsia. In addition to pregnancy, relaxin may also play a functional role in the uterus during the menstrual cycle, and modified relaxin activity may contribute to gynecological disorders such as uterine fibrosis and endometriosis. Despite over 75 years of research, we still have a limited understanding of relaxin's broad roles in the uterus, particularly as there are significant species differences in its synthesis and activity, which restricts the use of animal models for human-centric questions. Here, we review current knowledge regarding relaxin actions in the human uterus during the menstrual cycle and in early pregnancy, with a focus on its potential roles in various gynecological disorders, as well as the pregnancy disorders such as preeclampsia, recurrent miscarriage, and early pregnancy loss.