The type IBMP receptor BmprIB is essential for female reproductive function

Maintenance of female reproductive competence depends on the actions of sev eral hormones and signaling factors. Recent reports suggest roles for bone morphogenetic proteins (BMPs) in early stages of folliculogenesis, A role f or the type I BMP receptor BmprlB as a regulator of ovulation rates in shee p has been described recently, but little is known about the roles of BMP s ignaling pathways in other aspects of reproductive function. We report here that BMPRIB is essential for multiple aspects of female fertility. Mice de ficient in BmprlB exhibit irregular estrous cycles and an impaired pseudopr egnancy response. BmprlB mutants produce oocytes that can be fertilized in vitro, but defects in cumulus expansion prevent fertilization in vivo. This defect is associated with decreased levels of aromatase production in gran ulosa cells. Unexpectedly, levels of mRNA for cyclooxygenase 2, an enzyme r equired for cumulus expansion, are increased. BmprlB mutants also exhibit a failure in endometrial gland formation. The expression of BmprlB in uterin e linings suggests that these defects are a direct consequence of loss of B MP signaling in this tissue. In summary, these studies demonstrate the impo rtance of BMP signaling pathways for estrus cyclicity, estradiol biosynthes is, and cumulus cell expansion in vivo and reveal sites of action for BMP s ignaling pathways in reproductive tissues.