The type I BMP receptor BmprIB is essential for female reproductive function

Abstract

Maintenance of female reproductive competence depends on the actions of several hormones and signaling factors. Recent reports suggest roles for bone morphogenetic proteins (BMPs) in early stages of folliculogenesis. A role for the type I BMP receptor BmprIB as a regulator of ovulation rates in sheep has been described recently, but little is known about the roles of BMP signaling pathways in other aspects of reproductive function. We report here that BMPRIB is essential for multiple aspects of female fertility. Mice deficient in BmprIB exhibit irregular estrous cycles and an impaired pseudopregnancy response. BmprIB 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 granulosa cells. Unexpectedly, levels of mRNA for cyclooxygenase 2, an enzyme required for cumulus expansion, are increased. BmprIB mutants also exhibit a failure in endometrial gland formation. The expression of BmprIB in uterine linings suggests that these defects are a direct consequence of loss of BMP signaling in this tissue. In summary, these studies demonstrate the importance of BMP signaling pathways for estrus cyclicity, estradiol biosynthesis, and cumulus cell expansion in vivo and reveal sites of action for BMP signaling pathways in reproductive tissues.

Temporal regulation of BMP2, BMP6, BMP15, GDF9, BMPR1A, BMPR1B, BMPR2 and TGFBR1 mRNA expression in the oocyte, granulosa and theca cells of developing preovulatory follicles in the pig

“…This is in accordance with the phenotype observed in Bmp15 null mice where no apparent defects in follicular development were observed; but ovulation rate was lower and the ovulated oocytes showed reduced developmental potential (Yan et al 2001, Su et al 2004. Interestingly, the Bmpr1b null mice exhibited defects in cumulus expansion which, in turn, prevented in vivo fertilization (Yi et al 2001). Moreover, recent results obtained in two different mouse studies showed that BMP15 is likely involved in cumulus expansion (Gueripel et al 2006, Yoshino et al 2006.…”

EpithelialBmpr1aregulates differentiation and proliferation in postnatal hair follicles and is essential for tooth development

“…Bmpr1a null/+ males homozygous for bcre-32 were crossed with females of genotype Bmpr1a cl/cl . In addition, we used mice carrying a null allele of Bmpr1b (Bmpr1b null ) (Yi et al, 2001): Bmpr1a null/+ ; Bmpr1b null/+ males homozygous for bcre-32 were crossed with Bmpr1a cl/cl ; Bmpr1b null/+ females. PCR detection of wild-type, floxed and recombined Bmpr1a alleles was as described previously (Mishina et al, 2002).…”

Physiological effects of major genes affecting ovulation rate in sheep

“…The ALK6 knockout mouse does not display the same phenotype as the Booroola ewe [36]. ALK6 knockout mice appear to have normal ovarian follicular development and ovulation rates although there is a reduction in fertility perhaps caused by the failure of normal cumulus expansion.…”