Hormonal control of vas deferens fluid volume and aquaporin expression in rats
Precise regulation of vas deferens fluid volume which is important for sperm survival might be influenced by testosterone. In order to investigate changes in vas deferens fluid volume and aquoporins (AQP) isoforms expression under testosterone influence, orchidectomized Sprague–Dawley rats were given 125 and 250 µg/kg/day testosterone with or without flutamide, an androgen receptor blocker or finasteride, a 5alpha-reductase inhibitor for seven consecutive days. Following treatment completion, vas deferens was perfused and changes in the fluid secretion rate and osmolality were determined in the presence of acetazolamide. Rats were then sacrificed and vas deferens was harvested for histology, tissue expression and distribution analyses of AQP-1, AQP-2, AQP-5, AQP-7 and AQP-9 proteins by Western blotting and immunohistochemistry, respectively. Our findings indicate that testosterone causes vas deferens fluid secretion rate to increase, which was antagonized by acetazolamide. Fluid osmolality increased following testosterone treatment and further increased when acetazolamide was given. Co-administration of flutamide or finasteride with testosterone causing both fluid secretion rate and osmolality to decrease. Histology revealed increased size of vas deferens lumen with increased thickness of vas deferens stroma. Expression of AQP-1, AQP-2 and AQP-9 were detected in vas deferens but not AQP-5 and AQP-7, and the levels of these proteins were increased by testosterone treatment mainly at the apical membrane of vas deferens epithelium. In conclusion, increased in vas deferens fluid secretion rate under testosterone influence mediated via the up-regulation of AQP-1, 2 and 9 might be important for vas deferens fluid homeostasis in order to ensure normal male fertility.
KeywordsAQP isoforms Vas deferens Testosterone Acetazolamide
This study was funded by Fundamental research Grant Scheme (FP025-2014A)and PPP Grant (PG230-2015B), University of Malaya, Kuala Lumpur, Malaysia.
NSKR, NG and KK performed the research; NSKR, NG analyzed the data; NSKR wrote the preliminary manuscript while NS critically evaluates the manuscript and prepared the final proof.
Compliance with ethical standards
Conflict of interest
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
- Chinigarzadeh A, Muniandy S, Salleh N (2016) Estradiol, progesterone and genistein differentially regulate levels of aquaporin (AQP)-1, 2, 5 and 7 expression in the uteri of ovariectomized, sex-steroid. Defic Rats Steroids 115:47–55. https://doi.org/10.1016/j.steroids.2016.08.007 CrossRefGoogle Scholar
- Duan L, Di Q (2017) Acetazolamide suppresses multi-drug resistance-related protein 1 and P-glycoprotein expression by inhibiting aquaporins expression in a mesial temporal epilepsy rat model medical science monitor: international. Med J Exp Clin Res 23:5818–5825Google Scholar
- Gholami K, Muniandy S, Salleh N (2013) In-vivo functional study on the involvement of CFTR, SLC26A6, NHE-1 and CA isoenzymes II and XII in uterine fluid pH, volume and electrolyte regulation in rats under different sex-steroid influence. Int J Med Sci 10:1121–1134. https://doi.org/10.7150/ijms.5918 CrossRefGoogle Scholar
- Giribabu N, Karim K, Kilari EK, Kassim NM, Salleh N (2018) Anti-inflammatory, antiapoptotic and proproliferative effects of vitis vinifera seed ethanolic extract in the liver of streptozotocin-nicotinamide-induced type 2 diabetes in male rats. Can J Diabetes 42:138–149. https://doi.org/10.1016/j.jcjd.2017.04.005 CrossRefGoogle Scholar
- Gu F et al (2003) Testosterone up-regulates aquaporin-4 expression in cultured astrocytes vol 72. https://doi.org/10.1002/jnr.10603
- Hermo L, Schellenberg M, Liu LY, Dayanandan B, Zhang T, Mandato CA, Smith CE (2008) Membrane domain specificity in the spatial distribution of aquaporins 5, 7, 9, and 11 in efferent ducts and epididymis of rats. J Histochem Cytochem 56:1121–1135. https://doi.org/10.1369/jhc.2008.951947 CrossRefGoogle Scholar
- Hu Q, Jin J, Zhou H, Yu D, Qian W, Zhong Y, Zhang J, Tang C, Liu P, Zhou Y, Wang X, Sheng L (2018) Crocetin attenuates DHT-induced polycystic ovary syndrome in mice via revising kisspeptin neurons. Biomed Pharmacother 107:1363–1369. https://doi.org/10.1016/j.biopha.2018.08.135 CrossRefGoogle Scholar
- Khadijah Ramli NS, Giribabu N, Muniandy S, Salleh N (2018) Testosterone up-regulates vacuolar ATPase expression and functional activities in vas deferens of. Orchid Rats Theriogenol 108:354–361. https://doi.org/10.1016/j.theriogenology.2017.12.035 CrossRefGoogle Scholar
- Lu Y, Li D, W Bi Y, Yu ZM, li H X (2008a) Expression and immunohistochemical localization of aquaporin-1 in male reproductive organs of the mouse 37. https://doi.org/10.1111/j.1439-0264.2007.00827.x
- Mohd Mokhtar H, Giribabu N, Kassim N, Muniandy S, Salleh N (2014) Testosterone decreases fluid and chloride secretions in the uterus of adult female rats via down-regulating cystic fibrosis transmembrane regulator (CFTR) expression and functional activity J Steroid Biochem Mol Biol 144:361–372 https://doi.org/10.1016/j.jsbmb.2014.08.007 CrossRefGoogle Scholar
- Ramli NS, Giribabu N, Muniandy S, Salleh N (2016) Testosterone regulates levels of cystic fibrosis transmembrane regulator, adenylate cyclase, and cAMP in the seminal vesicles of orchidectomized rats. Theriogenology 85:238–246. https://doi.org/10.1016/j.theriogenology.2015.09.036 CrossRefGoogle Scholar
- Shahzad H, Giribabu N, Karim K, Muniandy S, Kassim NM, Salleh N (2017) Quercetin alters uterine fluid volume and aquaporin (AQP) subunits (AQP-1, 2, 5 & 7) expression in the uterus in the presence of sex-steroids in rats. Reprod Toxicol (Elmsford. NY) 69:276–285. https://doi.org/10.1016/j.reprotox.2017.03.012 CrossRefGoogle Scholar