Abstract
Busulfan is an alkane sulphonate currently used as an anticancer drug and to prepare azoospermic animal models, because it selectively destroys differentiated spermatogonia in the testes. However, few studies have focussed on the exact effects of busulfan treatment on the epididymis currently. The present study assessed the effect of busulfan on epididymal morphology and the blood–epididymis barrier in mice. We treated mice with a single injection of busulfan and detected the effect at different time points. We showed that busulfan was toxic to the morphological structure and function of the epididymis. Furthermore, busulfan treatment down-regulated the epididymal expression of vimentin and zonula occludens-1 (ZO-1) at the mRNA and protein levels. In addition, there was an increase in total androgen receptor (AR) levels, whereas the estrogen receptor-α (ER-α) levels were reduced, both in the caput and cauda regions after busulfan treatment, which may be secondary to the testicular damage. In conclusion, our study describes the effects of busulfan administration on the mouse epididymis and also provides a potential understanding of male infertility arising from chemotherapy-related defects in the epididymis.
Highlights
The epididymis plays an important role in post-testicular sperm maturation including the acquisition of forward motility and fertilizing ability [1,2]
In support of this view, early studies demonstrated that the caput and corpus provide microenvironments for sperm maturation, and that the cauda region primarily serves as a storage site for functional spermatozoa [5,6]
We found a significant increase in androgen receptor (AR) expression level 4 weeks after busulfan treatment in the caput and cauda regions of the mouse epididymis
Summary
The epididymis plays an important role in post-testicular sperm maturation including the acquisition of forward motility and fertilizing ability [1,2]. The epididymis is divided into four main anatomical regions: the initial segment (only present in rodents), the caput, the corpus and the cauda, with each epididymal region performing separate functions essential to the different steps of sperm maturation. The adult epididymal epithelium consists of different cell types, including principal, clear, basal, halo, narrow, and apical cells, which form a monolayer surrounding the lumen [3]. These cell types within the epididymal epithelium have individual functions, they communicate with each other to maintain sperm maturation and storage via different cell junctions [7].
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