Functional expression of G protein‐coupled receptor 30 in immature rat epididymal epithelium

Abstract

The aim of this study is to investigate the functional role of G protein-coupled receptor 30 (GPR30) in the epididymis. We found that GPR30 is expressed in the epithelium of the immature rat epididymis and is involved in chloride secretion into the caudal epididymis lumen. The short-circuit current (Isc) experiments showed that in primary cultured caudal epididymis epithelium, activation of GPR30 by its specific agonist G1 induced a mono-phasic current increase, and G15, the specific antagonist of GPR30, could completely inhibit the current induced by G1. The G1-induced Isc was largely blocked by application of the non-specific chloride channel inhibitor diphenylamine-dicarboxylic acid (DPC), or by the cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTR , suggesting that the current was mainly mediated through CFTR. In addition, after stimulating GPR30 by G1, the intracellular concentration of cAMP in the epithelium was significantly increased, indicating that the cAMP signal pathway is involved and could be responsible for the CFTR activation. Finally, to further investigate the function of GPR30 in vivo, G15 was administrated into rats subcutaneously. The osmotic pressure of the micro perfusion solution from epididymis was measured and the sperms were collected. Results showed that there was an osmotic pressure increase of the perfusion solution from G15 treated rats. When the GPR30 was inhibited by G15 endogenously, the motility of sperms decreased. Our data demonstrated that GPR30 is involved in the formation of caudal epididymis fluid micro-environment thus affecting sperm motility.

Aerobic exercises regulate the epididymal anion homeostasis of high-fat diet-induced obese rats through TRPA1-mediated Cl− and HCO3− secretion

“…In line with the pro-secretion function of TRPA1 in the colon, the activation of CFTR was a downstream event of TRPA1 activation ( Figure 4 ). CFTR is a cAMP-regulated channel that ensures transepithelial transport of Cl − and HCO 3 − [ 30 , 42 ]. AC activation is an important upstream cellular event before the opening of CFTR.…”

Function and therapeutic potential of GPCRs in epididymis

“…GPER has been detected in many male reproductive structures, such as the testes (Cassault-Meyer et al , 2014;Gautier et al , 2016;Lucas et al , 2010), spermatozoa (Arkoun et al , 2014;Cassault-Meyer et al , 2014;Gautier et al , 2016), and prostate (Rago et al , 2016). It has also been found in the efferent ductules and epididymis (Cao et al , 2017;Hess et al , 2011;Katleba et al , 2015;Krejcirova et al , 2018;Lu et al , 2016;Malivindi et al , 2018;Martinez-Traverso et al , 2015;Menad et al , 2017;Pereira et al , 2014;Rago et al , 2018), indicating that GPER may play important roles in sperm maturation, protection and storage (Table 1). For instance, in the corpus epididymis of postnatal pigs, GPER participates in sperm maturation by affecting the formation of the blood-epididymal barrier (Katlebaet al , 2015).…”

Function and therapeutic potential of G protein‐coupled receptors in epididymis

“…GPER has been detected in many male reproductive structures, such as the testes (Cassault-Meyer, Gress, Seralini, & Galeraud-Denis, 2014;Gautier et al, 2016;Lucas et al, 2010), spermatozoa (Arkoun et al, 2014;Cassault-Meyer et al, 2014;Gautier et al, 2016), and prostate (Rago, Romeo, Giordano, Ferraro, & Carpino, 2016). It has also been found in the efferent ductules and epididymis (Cao et al, 2017;Hess et al, 2011;Katleba et al, 2015;Krejcirova et al, 2018;Lu et al, 2016;Malivindi, Aquila, & Rago, 2018;Martinez-Traverso & Pearl, 2015;Menad et al, 2017;Pereira et al, 2014;Rago et al, 2018), indicating that GPER may play important roles in sperm maturation, protection and storage (Table 1). For instance, in the corpus epididymis of postnatal pigs, GPER participates in sperm maturation by affecting the formation of the blood-epididymal barrier (Katleba et al, 2015).…”

“…For instance, in the corpus epididymis of postnatal pigs, GPER participates in sperm maturation by affecting the formation of the blood-epididymal barrier (Katleba et al, 2015). In the caudal epididymal epithelium in immature rats, GPER induces a pathway involved in cAMP-CFTR-chloride secretion to regulate osmotic pressure in response to a perfusion solution and thus affects sperm motility (Figure 1) (Cao et al, 2017).…”