Changes in porcine cauda epididymal fluid proteome by disrupting the HPT axis: Unveiling potential mechanisms of male infertility

Male infertility or subfertility is frequently associated with disruption of the hypothalamic–pituitary–testis axis events, like secondary hypogonadism. However, little is known how this condition affects the proteomic composition of the epididymal fluid. In the present study, we evaluated the proteomic changes in the cauda epididymal fluid (CEF) in a swine model of secondary hypogonadism induced by anti‐GnRH immunization using multidimensional protein identification technology. Seven hundred and eighteen proteins were identified in both GnRH‐immunized and control groups. GnRH immunization doubled the number of proteins in the CEF, with 417 proteins being found exclusively in samples from GnRH‐immunized boars. CEF from GnRH‐immunized boars presented an increase in the number of proteins related to cellular and metabolic processes, with affinity to organic cyclic compounds, small molecules, and heterocyclic compounds, as well changed the enzymatic profile of the CEF. Also, a significant increase in the number of proteins associated to the ubiquitin–proteasome system was identified in CEF from GnRH‐immunized animals. These results bring strong evidence of the impact of secondary hypogonadism on the epididymal environment, which is responsible for sperm maturation and storage prior ejaculation. Finally, the differently expressed proteins in the CEF are putative seminal biomarkers for testicular and epididymal disorders caused by secondary hypogonadism. The data obtained in the present study using a swine model for secondary hypogonadism provides novel insights into the changes in the cauda epididymis milieu and the possible implications on sperm maturation, storage, and quality. Such approach allowed us to (a) understand the changes in the proteomic landscape of the cauda epididymal fluid caused by GnRH immunological blocking and to (b) identify biomarker candidates for this condition in man.