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

Abstract

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.

Immunocastration in adult boars as a model for late‐onset hypogonadism

“…20 Evidence also supports the use of IC boars as a model for the study of secondary hypogonadism in humans. [21][22][23] Regression of the reproductive tract in immunocastrated male pubertal pigs is consistent with a loss of functional activity, as shown by the histological changes in testicular tissue. [24][25][26] Research findings suggest that the timing of vaccination (during either early or late sexual development stage) may play a crucial role in the extent of suppression of reproductive function 25 ; however, the underlying physiological mechanisms are unclear and merit further investigation.…”

“…This is equivalent to pigs been suggested as a suitable animal model for translational research because of the similarities in their reproductive processes with those of humans 20 . Evidence also supports the use of IC boars as a model for the study of secondary hypogonadism in humans 21–23 . Regression of the reproductive tract in immunocastrated male pubertal pigs is consistent with a loss of functional activity, as shown by the histological changes in testicular tissue 24–26 .…”

The significance of single-cell transcriptome analysis in epididymis research

“…Currently, it had been demonstrated that sperm in the epididymal corpus area possess a similar ability to cauda sperm, including capacitation, oocyte fertilization, and survival during cryopreservation ( Kunkitti et al, 2015 ; Kunkitti et al, 2016a ; Kunkitti et al, 2016b ). The cauda of the epididymis served as the final storage site for matured sperm prior to ejaculation ( Souza et al, 2020 ). In many animal species, sperm could maintain fertility for several weeks within this environment ( Esponda and Bedford, 1986 ).…”