Activin and inhibin signaling: From regulation of physiology to involvement in the pathology of the female reproductive system

Activins and inhibins - comprising activin A, B, AB, C and E, and inhibin A and B isoforms - belong to the transforming growth factor beta (TGFβ) superfamily. They regulate several biological processes, including cellular proliferation, differentiation and invasiveness, to enhance the formation and functioning of many human tissues and organs. In this review, we have discussed the role of activin and inhibin signaling in the physiological and female-specific pathological events that occur in the female reproductive system. The up-to-date evidence indicates that these cytokines regulate germ cell development, follicular development, ovulation, uterine receptivity, decidualization and placentation through the activation of several signaling pathways; and that their dysregulated expression is involved in the pathogenesis and pathophysiology of the numerous diseases, including pregnancy complications, that disturb reproduction. Hence, some of the isoforms have been suggested as potential biomarkers and therapeutic targets for the management of some of these diseases. Tackling the research directions highlighted in this review will enhance a detailed comprehension and the clinical utility of these cytokines.