Testosterone Upregulates Anion Secretion Across Porcine Vas Deferens Epithelia In Vitro1

Abstract

Testosterone induces and maintains prostaglandin endoperoxide synthase 2 (PTGS2, also known as cyclooxygenase 2) expression in vas deferens epithelial cells, but it remains unknown whether this has a physiological role in the context of male reproductive biology. Prostaglandins induce concentration-dependent increases in anion secretion in porcine vas deferens epithelial cell (1 degrees PVD) monolayers, where bicarbonate contributes to cAMP-stimulated anion secretion. Moreover, bradykinin induces anion secretion across 1 degrees PVD monolayers that is indomethacin sensitive, and both PTGS2 and PTGS1 are expressed in this model system. Therefore, it was hypothesized that testosterone modulates anion secretion across vas deferens epithelia via PTGS-dependent pathways and prostaglandin synthesis. Porcine vas deferens epithelial cells were isolated and cultured as monolayers on permeable supports until assayed in modified Ussing chambers. RNA and protein were isolated concurrently for semiquantitative expression analysis. Testosterone upregulated basal and bradykinin-induced short-circuit current across 1 degrees PVD monolayers, indicative of anion secretion. Testosterone also induced greater transepithelial electrical resistance. Increases in anion secretion were associated with preferential upregulation of PTGS2 at the mRNA and protein levels. In addition, testosterone induced greater basal and bradykinin-induced anion secretion across vas deferens epithelial cells isolated from the distal segment of the duct. Taken together, these results suggest that testosterone upregulates epithelial responsiveness to acute modulations of anion secretion (likely bicarbonate secretion), which ultimately modifies the environment to which sperm are exposed.

Non-obstructive vas deferens and epididymis loss in cystic fibrosis rats

“…Testosterone production begins at approximately E15.5 in the male rat fetus and is believed to stabilize the Wolffian duct by inhibiting its involution. A perinatal testosterone surge may also activate fluid and electrolyte transport through CFTR in tissues such as the vas deferens [15][16] (see also below). In female rats, onset of Wolffian duct involution becomes apparent by E17.5-E18.5 [17][18][19] .…”

Rats undernourished in utero have altered Ca2+signaling and reduced fertility in adulthood

“…Alterations in ionic transport processes – possibly those of Ca 2+ – could also have affected the normal regulation of the luminal environment to which sperm cells are exposed (Pierucci‐Alves et al. , ). This proposal is supported by the observation that intracellular Ca 2+ seems to be a key regulator of transepithelial fluxes in the efferent ducts and epididymis (Belleannée et al.…”

“…Possibly, and despite the preserved plasma ionized Ca 2+ , the vas deferens was adversely impacted in terms of Ca 2+ -modulated processes, as demonstrated for bone (Ashton et al 2007). Alterations in ionic transport processespossibly those of Ca 2+could also have affected the normal regulation of the luminal environment to which sperm cells are exposed (Pierucci-Alves et al 2009. This proposal is supported by the observation that intracellular Ca 2+ seems to be a key regulator of transepithelial fluxes in the efferent ducts and epididymis (Belleann ee et al 2009), as it is in other epithelia (Jung and Lee 2014).…”

“…In this context, the vas deferens deserves special attention because it tightly regulates the luminal environment to which sperm cells are exposed (Pierucci‐Alves et al. , ) during their storage (Peirce et al. ) and passage from the epididymis to the urethra (Westfall and Westfall ; Koslov and Andersson ).…”

“…Although there is a general understanding of the links between nutritional status and sex hormone regulation, little is known about the mechanisms that lead to the dysfunction of male reproductive organs, and much less is known regarding possible adaptive responses. In this context, the vas deferens deserves special attention because it tightly regulates the luminal environment to which sperm cells are exposed (Pierucci-Alves et al 2009 during their storage (Peirce et al 2003) and passage from the epididymis to the urethra (Westfall and Westfall 2001;Koslov and Andersson 2013). For these reasons, alterations in this organwhich is less investigated than others in the genital tractare critical for fertility impairment (Sato et al 2005;Chen et al 2012).…”