Structural modeling and mRNA expression of epididymal ß-defensins in GnRH immunized boars: A model for secondary hypogonadism in man.

ABSTRACT

Human secondary hypogonadism is associated with impaired testicular function, however, little is known about its impact on sperm epididymal maturation. Endocrine disruption in the epididymis could impair the secretion of key proteins, such as ß-defensins, responsible for spermatozoa maturation during epididymal transit. This study evaluated the sequence and structural similarities between porcine epididymal ß-defensins porcine ß-defensins (pBD3), pBD4, pBD125, and pEP2C and their human homologs using bioinformatics integrated with information derived from protein databanks. We then verified whether the expression of pBD3, pBD4, pBD125, and pEP2C genes in the testis and epididymis are influenced by disruption of the hypothalamic-pituitary-testicular (HPT) axis in a pig model for male human secondary hypogonadism. Upon modeling porcine ß-defensins, structural and functional analysis confirmed the presence of motifs associated with ß-defensin function, validating the models generated in silico. pBD3 and pBD4 showed acceptable structural alignments with human ß-defensins BDEF103 and BDEF110, respectively. In addition, evaluation of hormonal regulation of ß-defensins was assessed by analyzing the expression of these four ß-defensins in adult boars immunized against gonadotropin-releasing hormone (GnRH). Our results indicate that HPT axis disruption modifies the expression of pBD3, pBD4, pBD125, and pEP2C in boar testis and epididymis, suggesting an endocrine-dependent regulation of ß-defensins in swine epididymis. In conclusion, sequence and structural homology between pBD3 and pBD4 and their human homologs provide a basis for using the pig as a model for the study of human secondary hypogonadism. Further investigation of the human homologs in hypogonadal men could elucidate the connections between fertility and epididymal expression of ß-defensins.