BMP4 as a Potential Molecular Link between Obesity and Female Fertility

Bone morphogenetic protein 4 (BMP4) is a member of the transforming growth factor β (TGF-β) superfamily. Accumulating evidence indicates that BMP4 is widely expressed in female reproductive tissues, including the ovary and endometrium. Therefore, this review summarizes the roles of BMP4 in regulating the physiological functions of the ovary and endometrium, including folliculogenesis, ovarian steroidogenesis, endometrial decidualization and regulation of maternal-foetal immunity. Notably, increasing studies revealed that BMP4 is also critically involved in obesity. Given the continuously rising prevalence of obesity worldwide, this review further summarizes emerging evidence on the role of BMP4 in adipogenesis, the shift between white adipose tissue (WAT) and brown adipose tissue (BAT) and metabolic dysregulation. To further elucidate the role of BMP4, we also summarize the expression patterns and potential mechanisms in reproductive disorders and obesity. We found that dysregulated BMP4 expression has been reported in polycystic ovary syndrome (PCOS), recurrent spontaneous abortion (RSA) and obesity, suggesting a potential molecular link between obesity and female fertility. Hence, the potential role of BMP4 between obesity and women's fertility is further discussed and may provide direction for further reproductive-related research. This hypothesis may guide further studies to explore the underlying mechanisms and their translational implications.