Decidualization is an intricate biological process where extensive morphological, functional, and genetic changes take place in endometrial stromal cells to support the development of an implanting blastocyst. Deficiencies in decidualization are associated with pregnancy complications and reproductive diseases. Decidualization is coordinately regulated by steroid hormones, growth factors, and molecular and epigenetic mechanisms. Transforming growth factor β (TGFβ) superfamily signaling regulates multifaceted reproductive processes. However, the role of TGFβ signaling in uterine decidualization is poorly understood. Recent studies using the Cre-LoxP strategy have shed new light on the critical role of TGFβ signaling machinery in uterine decidualization. Herein, we focus on reviewing exciting findings from studies using both mouse genetics and in vitro cultured human endometrial stromal cells. We also delve into emerging mechanisms that underlie decidualization, such as non-coding RNAs and epigenetic modifications. We envision that future studies aimed at defining the interrelationship among TGFβ signaling circuitries and their potential interactions with epigenetic modifications/non-coding RNAs during uterine decidualization will open new avenues to treat pregnancy complications associated with decidualization deficiencies.
Keywords: Activin; BMP; Decidualization; SMAD; TGF-beta; TGFBR1.