119. THE EFFECT OF BMPR-IB IMMUNIZATION IN IMMATURE FEMALE MICE

Abstract

The female reproductive system is regulated by well known endocrine signaling components and the less well understood autocrine and paracrine signaling components by growth factors and their receptors. The type I Bone Morphogenetic Protein Receptor IB (BMPR-IB) is a serine/threonine kinase that facilitates the signaling of various TGF-β family members. BMPR-IB is believed to have a substantial role in reproduction as demonstrated by the hyperprolific effect on ovulation in Booroola ewes which harbor a natural BMPR-IB receptor mutation, as well as the sterility induced by the BMPR-IB knockout in female mice. Maturation of the ovary and enhancement of follicular growth are known to be dependent on gonadotrophin stimulation from the pituitary. This study aims to elucidate the role of BMPR-IB in the female reproductive system by passive immune neutralization. Immature female mice (21 days old) were passively immunized against BMPR-IB via subcutaneous injections of 100 μl PBS containing anti BMPR-IB Ig in the absence and presence of equine chorionic gonadotrophin (eCG). The preparations where administered on day one and three of a four day experiment. On day four mice were asphyxiated with CO₂ and the ovaries were removed and weighed. In immature mice immunization against BMPR-IB ovarian weights were not different from control, while eCG significantly increased ovarian weight compared to the controls. In combination immunization against BMPR-IB further augmented the gonadotrophin-stimulated increase in ovarian weight to a significant degree. The suppressive effect of BMPR-IB signaling on follicular development in response to gonadotrophin stimulation indicates a possible developmental role of this receptor in the initiation of follicle growth in response to increased circulatory gonadotrophins and prevention of precocious puberty.