228. In vivo evidence for a role of bone morphogenetic protein-4 in ovarian function

Abstract

Bone morphogenetic proteins (BMPs) were first identified on the basis of their bone inducing capacity, and later shown to be members of the transforming growth factor β (TGF β) super family. Nilsson et al.¹ studied the effect of BMP-4 on follicular development in rat ovaries and found that the addition of BMP-4 to whole ovary cultures led to more numbers of developing primary follicles but less numbers of primordial follicles. Their studies indicate that BMP-4 acts as a transition factor for the conversion of primordial follicles to primary follicles. To test this hypothesis in-vivo, we conducted passive immunization studies against BMP-4 in prepubertal female mice.

The mice were divided in to four groups (n = 5), and given daily SC injections of the following treatment: anti BMP-4 (50 μg), PMSG (10 IU) (pregnant mare serum gonadotropin) with and without anti BMP-4 (0.5 mg/mL) and PBS for 3 days. All experimentation was approved by animal ethics committee, University of New England, Armidale, NSW. On the fourth day the mice were killed and the ovaries removed and weighed. The mice treated with anti BMP-4 had significantly smaller ovaries (4.1 ± 0.4 mg) than the control group (8.6 ± 0.9 mg). PMSG stimulated ovarian weight (21.0 ± 1.2 mg) but anti BMP-4 (23.2 ± 1.3 mg) did not significantly affect the weight of the stimulated ovaries. This data confirms BMP-4 is important in ovarian function; however, it is unclear whether this effect is on the ovary directly or via FSH.

   (1) Nilsson, E. E., Skinner, M.K. (2003). Bone morphogenetic protein-4 acts as an ovarian follicle survival factor and promotes primordial follicle development. Biology of Reproduction 69, 1265–1272.