Aberrant Expression Levels of Androgen Receptor and SRD5A2 in Epididymal Epithelial Cells of Crossbred Infertile Cattle–Yak

TL;DR

This study finds that infertility in hybrid cattle–yaks may be caused by lower levels of SRD5A2 in the epididymis, not AR deficiency.

Contribution

The study identifies SRD5A2 deficiency in hybrid cattle–yaks as a potential cause of infertility, distinct from AR expression.

Findings

AR signal intensity was higher in hybrid cattle–yaks compared to yaks, ruling out AR deficiency as a cause of infertility.

SRD5A2 signal intensity was lower in hybrid cattle–yaks, suggesting a disruption in androgen signaling and sperm maturation.

Stable AR and SRD5A2 levels in yaks indicate normal epididymal function in fertile animals.

Abstract

This study explores the infertility observed in hybrid male cattle–yaks, focusing on the roles of the androgen receptor (AR) and 5α-reductase isoform 2 (SRD5A2) in the epididymis. Although both species belong to the same subfamily and share chromosome numbers, hybrid males are sterile due to abnormalities in sperm production. Recent analyses of gene expression in both the testis and epididymis have provided insights into the mechanisms underlying this infertility. The maturation of sperm, which is crucial for fertilisation, is believed to be dependent on androgens, with the AR being activated by dihydrotestosterone, a derivative of testosterone processed by SRD5A2 in epididymal cells. This research involved comparing the immuno-expression levels of the AR and SRD5A2 in the epididymal caput of yaks and hybrid cattle–yaks. The findings revealed that in yaks, AR signal intensity remained stable during maturation, while in hybrid cattle–yaks, AR signal intensity was significantly higher in principal cells compared to yaks of the same age. This indicates that AR deficiency is not the cause of hybrid sterility. Conversely, this study found that SRD5A2 signal intensity was stable during maturation in yak epididymal epithelial cells, whereas hybrid cattle–yaks exhibited lower SRD5A2 levels in cells compared to yaks of the same age. This deficiency in SRD5A2 production is suggested to contribute to hybrid infertility by impairing AR signal transduction and disrupting sperm physiology.

Although yaks and cattle belong to the same Bovinae subfamily and have the same number of chromosomes, hybrid males are sterile because of the inactivation or abnormality of gene expression related to the production of healthy normal sperm. Recently, the analysis of gene expression not only in the testis but also in the epididymis has offered hints about the mechanism of infertility, because the epididymis supports the maturation of sperm in acquiring the capacity of fertilisation. Sperm maturation processes have been thought to be androgen-dependent, and the androgen receptor (AR) can be activated by dihydrotestosterone converted from plasma testosterone by the 5α-reductase isoform 2 (SRD5A2) in epididymal cells. In the present study, we investigated the immuno-expression levels of the AR and SRD5A2 in the epithelial cells of the hybrid cattle–yak epididymal caput in comparison with yak samples using image analysis. Epididymal tissues from yaks (1–3 years of age) and hybrid cattle–yaks (2 years of age) were used in this study. In yaks, AR signal intensity did not show any changes in epididymal epithelial cells during maturation. However, in 2-year-old hybrid cattle–yaks, AR signal intensity was significantly higher in the principal cells of the epididymis compared to that of yaks of the same age, indicating that hybrid sterility is not likely related to AR deficiency in the epididymal epithelium. On the other hand, SRD5A2 signal intensity was stable during maturation in the epithelial cells of the yak epididymis. However, the epididymal SRD5A2 signal intensity in the epithelial cells of the hybrid cattle–yak was lower than that of the yak. This suggests that a deficiency in SRD5A2 production in the epididymis may result in hybrid infertility, as it can subsequently cause incomplete AR signal transduction and altered spermatozoa physiology.

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