Dynamic expression of bone morphogenetic protein 4 in reproductive organs of female mice

Various members of the bone morphogenetic protein (BMP) family have been shown to regulate mammalian follicular development by affecting granulosa cell proliferation and steroidogenesis. In situ hybridization studies have shown expression of BMPR1A, BMPR1B, and BMPR2 in the granulosa cells and oocyte of most of the follicles in the ovary, suggesting that these cells have the capacity to respond to BMP signaling. Although much is known about BMP4 signaling, its expression pattern in the female reproductive tract (FRT) is still unclear. The objective of the current study was to characterize the expression of BMP4 and its downstream target proteins (pSMAD1/5/8) in the FRT. In the ovary, BMP4 protein was detected in all the stages of follicular development. Staining for pSMAD1/5/8 was observed in granulosa cells and oocytes of all the stages of follicular development including primordial follicles, suggesting that these follicles are responsive to autocrine/paracrine BMP signaling. In the uterus, BMP4 and pSMAD1/5/8 staining was observed in all three compartments and strongest expression was observed during the estrus phase. BMP4- and pSMAD1/5/8-specific staining was also observed in oviductal epithelium. Different forms (apparent MW: 50, 35, and 15  kDa) of BMP4 were detected in mouse ovary by western blot analysis. In conclusion, these results have defined BMP4 and pSMAD1/5/8 protein expression in the mouse FRT and highlighted the importance of BMP4 in folliculogenesis.