Investigating the Role of Bone Morphogenetic Protein Receptor IB and Putative Ligands in Reproductive Development and Steroidogenic Regulation in Male Mice

The aim of this research is to elucidate the function of BMPR-IB using passive neutralization of BMPR-IB in vivo and in vitro placing specific attention to its role in the male reproductive system, given the importance of BMPR-IB in females and the lack of publications available for its function in males. BMP and BMP receptor mRNA expression was also screened in male reproductive tissues to establish the presence and relative quantitation of these genes. We hypothesize that BMPR-IB has important roles in male reproduction based on a limited amount research investigating BMPs and their receptors in this area and the fact that the receptor has crucial roles in females. The significance of any findings could be translated in numerous fields and includes a greater understanding of normal male reproductive physiology, a better understanding of abnormalities present in male infertility and cancer of male reproductive organs as well as the identification of possible future therapeutic targets

Steroidogenic Enzyme Gene Expression and Testosterone Production are Developmentally Modulated by Bone Morphogenetic Protein Receptor-1B in Mouse Testis

Bone morphogenetic proteins (BMPs) and receptors (BMPR-1A, BMPR-1B, BMPR-2) have been shown to be vital for female reproduction, while their roles in males are poorly described. Our study was undertaken to specify the function of BMPR-1B in steroidogenic enzyme gene expression, testosterone production and reproductive development in male mice, given that Bmpr1b mRNA is expressed in mouse testis and Bmpr1b knockout results in compromised fertility. Male mice were passively immunized for 6 days with anti-BMPR-1B in the presence or absence of exogenous gonadotrophins. We then measured the effects of anti-BMPR-1B on testicular hydroxysteroid dehydrogenase isoforms (Hsd3b1, Hsd3b6, and Hsd17b3) and aromatase (Cyp19) mRNA expression, testicular and serum testosterone levels, and testis and seminal vesicle weight. In vitro testosterone production in response to anti-BMPR-1B was determined using testicular culture, and Leydig cell culture in the presence or absence of gonadotrophins. In Leydig cell culture the contribution of seminiferous tubules and Leydig cells were examined by preconditioning the media with these testicular constituents. In adult mice, anti-BMPR-1B increased testosterone and Hsd3b1 but decreased Hsd3b6 and Cyp19 mRNA. In adult testicular culture and seminiferous tubule conditioned Leydig cell culture, anti BMPR-1B reduced testosterone, while in normal and Leydig cell conditioned Leydig cell culture it increased testosterone levels. In pubertal mice, anti-BMPR-1B reduced gonadotrophin stimulated seminal vesicle growth. In conclusion, BMPR-1B has specific developmental functions in the autocrine and paracrine regulation of testicular steroidogenic enzyme gene expression and testosterone production in adults and in the development of seminal vesicles during puberty