Effects of Spironolactone (Aldosterone Antagonist) on Electrolyte and Water Content of the Cauda Epididymidis and Fertility of Male Rats

Abstract

It has previously been shown that the rat cauda epididymidis actively reabsorbs Na+ in exchange with K+. This coupled Na+/K+ transport is stimulated by aldosterone. These transport processes create a low Na+ and high K+ environment which appears to be (in part) responsible for sperm quiescence during storage. The effects of aldosterone antagonist, spironolactone, on the electrolyte and water content of the cauda epididymidis, sperm motility initiation and fertility of male rats were investigated in the present study. It was found that treatment of rats with spironolactone (10 mg/kg per day for 4 to 17 days) led to a significant fall in K+ (18%) and sperm (21.5%) concentrations in the cauda epididymal fluid. However, the Na+ concentration remained unchanged. The fall in sperm concentration may be taken to indicate an increase in fluid volume which is secondary to an inhibition of water absorption. When corrected for an increase in volume, there was no change in the amount of K+ in the fluid but the amount of intraluminal Na+ was increased. Despite a fall in K+ and sperm concentration, the capacity of the cauda sperm to initiate motility and fertility of the animals were apparently not affected by spironolactone treatment. It is concluded that the fertility capacity of spermatozoa is rather resistant to drugs which interfere with electrolyte and water transport across the caudal epididymal epithelium.

Adrenal independence of fluid and electrolyte reabsorption in the ductuli efferentes testis of the rat

“…The absence of an effect of adrenalectomy or spironolactone treatment on the masses of the testis and accessory glands in this study is in agreement with published reports in the rat which show that adrenalectomy (Feek, Tuzi & Edwards, 1989) and spironolactone treatment (Menard, Stripp & Gilette, 1974) do not affect chronic circulating testosterone levels, or mass of the testes or seminal vesicles (Wong & Lee, 1982). Turner & Cesarini (1983), however, did report a small but significant effect on seminal vesicle (but not testis) weight.…”

Circulating aldosterone induces the apical accumulation of the proton pumping V-ATPase and increases proton secretion in clear cells in the caput epididymis

“…If we assume that they are, then this would suggest that in the epididymis, direct effects of aldosterone would be restricted to clear cells. However, previous studies have shown long-term modulation of electrolyte and fluid transport in epididymal principal cells by aldosterone (3,29,58,65), indicating potential NR3C2-and HSD11␤2-independent signaling. Recent studies have indicated the existence of other aldosterone receptors in addition to the classic NR3C2 (32,56), and it remains possible that the response of epididymal principal cells to aldosterone could be attributed to these still incompletely characterized receptors.…”

“…Adrenalectomy or spironolactone treatment caused a decrease in Na ϩ reabsorption, which was followed by a decrease in water absorption resulting in a decrease in sperm concentration in the epididymis. The effect of adrenalectomy was partially reversed with aldosterone replacement (3,29,58,65). Importantly, the effect of spironolactone was not affected by simultaneous treatment with testosterone, demonstrating the specificity of spironolactone as a mineralocorticoid receptor (MR) antagonist in these experiments (58).…”

Epididymal Phenotype in Luteinizing Hormone Receptor Knockout Animals and Its Response to Testosterone Replacement Therapy1

“…Mature sperm are stored in distal cauda epididymis [1,2]. Although androgens are very important [1,2,7], other regulatory molecules are also involved in controlling epididymal functions [1,2,[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24].…”