Deletion of fetoplacental Fshr inhibits fetal vessel angiogenesis in the mouse placenta.

It has been shown in both human and mouse placentas that follicle stimulating hormone receptor (FSHR) is expressed in fetal vascular endothelium. There are conflicting reports, however, on the role of FSH to stimulate angiogenesis in vitro in cultured endothelial cells from umbilical veins. Therefore, in this study we undertook an in vivo approach utilizing Fshr null mice to definitively address this question. In the context where all pregnant dams have identical Fshr genotypes, we generated fetuses and associated fetal portions of placenta that were Fshr wt or Fshr null and analyzed angiogenesis within the placental labyrinths. Quantitative morphometric analyses of placentas obtained at mid-gestation revealed that the percentage of the placenta composed of labyrinth is significantly decreased in Fshr null placentas relative to wt placentas. Furthermore, data presented demonstrate that within the Fshr null labyrinths, fetal vessel angiogenesis was significantly reduced relative to wt labyrinths. The results obtained with this combination of in vivo and genetic approaches conclusively demonstrate that signaling through endothelial FSHR does indeed stimulate angiogenesis and that placental Fshr is essential for normal angiogenesis of the fetal placental vasculature.