GnRH immunization alters the expression and distribution of protein disulfide isomerases in the epididymis

Abstract

SUMMARYHypogonadism is defined as the inadequate gonadal production of testosterone. Low serum testosterone leads to infertility by impairing spermatogenesis and reducing sperm count, however, the impact of hypogonadism in epididymal sperm maturation is poorly understood. From the testis, spermatozoa are transported into the epididymis where they find a specific microenvironment composed of a complex mixture of proteins that facilitate sperm storage and maturation. Inside the epididymal ductule, spermatozoa undergo several changes, resulting in their becoming capable of fertilizing eggs. Protein disulfide isomerases (PDIs) are known to participate in the folding and assembly of secreted proteins in the endoplasmic reticulum. However, little is known about the control and function of PDIs in the testis and epididymis, particularly during male development. The aim of this work was to compare the expression and distribution of PDI and PDIA3 (ERp57) in the testis and epididymis of healthy and GnRH-immunized boars. We detected higher amounts of PDIA3 and PDI in sperm preparations and fluid from the proximal regions of the epididymis of healthy boars. However, we observed an increase in PDIA3 expression in the testis and cauda epididymis in the immunocastrated group. GnRH-immunized boars showed a marked increase in PDI content in cauda spermatozoa and fluid, indicating a possible endocrine dysregulation of PDI. The results of our study suggest that PDIs are associated with epididymal sperm maturation and may be attractive candidates for monitoring male fertility.

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

“…However, there is a gap in understanding how the epididymal milieu is impacted in pathological conditions, such as HPT‐axis disruption. By comparing the CEF proteome of healthy and GnRH‐immunized boars, a model for human secondary hypogonadism (Schorr‐Lenz et al, 2016; Weber, Alves, Abujamra, & Bustamante‐Filho, 2018), we observed a considerable effect in the protein composition, both quantitatively and qualitatively. Together with a better understanding of the impacts of HPT‐axis disruption in the CEF, differentially expressed proteins are putative seminal biomarkers for secondary hypogonadism.…”

Structural modeling and mRNA expression of epididymal β‐defensins in GnRH immunized boars: A model for secondary hypogonadism in man

“…Thus, in the current study, we evaluated the sequence and structural similarities of pBD3, pBD4, pBD125, and pEP2C with human homologs using state‐of‐the‐art bioinformatic tools integrated with information derived from protein databanks. Also, we verified if their expression in the testis and epididymis are regulated by the HPT axis in a pig model for male human secondary hypogonadism based in the immunization against GnRH (Schorr‐Lenz et al, ).…”

The epididymis and its role on sperm quality and male fertility

“…Not all of these major secreted proteins remain in the fluid: in the boar, RNAse 10 is present in the anterior caput fluid but is reabsorbed in the next zones, and almost no protein can be found distal to the caput region (Castella et al, 2004). The same pattern was observed for chaperones belonging to the protein disulfide isomerase (PDI) family in sperm and epididymal fluid from boars (Schorr-Lenz et al, 2016).…”