Figure 7

Estrogen and its inhibition in the male reproductive tract: a summary. In adult males, germ cells, as well as Leydig cells (LC) contain P450 aromatase and actively synthesize estrogen (E2), which produces a relatively high concentration in rete testis fluid. This luminal estrogen targets estrogen receptors that are abundant throughout the male reproductive tract, but particularly ERα that is localized in the efferent ductule epithelium, where its expression is more abundant than even the female reproductive tract. In the testis, E2 may also feedback to influence the function of LC and spermatids, either round spermatids (rs) or elongated spermatids (es). Estrogen's primary function in the male tract is the regulation of fluid reabsorption in the efferent ductules via ERα, which increases the concentration of sperm prior to entering the epididymis. Disruption of ERα, either in the knockout (αERKO) or by treatment with a pure antiestrogen ICI 182,780, results in a decrease in Na+ transport from lumen to interstitium and thus a decrease in water (H₂O) and fluid reabsorption. This inhibition is mediated by a decrease in the expression of NHE3 mRNA and protein and also decreases in carbonic anhydrase II (CAII) and aquaporin I (AQP-1) proteins. There is also an increase in cystic fibrosis transmembrane conductance regulator protein and mRNA, which adds to the NHE3 effect by secreting Cl^- into the lumen by the cystic fibrosis transmembrane conductance regulator (CFTR) [64]. This inhibition of fluid reabsorption results in the dilution of cauda epididymal sperm, disruption of sperm morphology, and eventual decreased fertility. In addition to this primary regulation of luminal fluids and ions, estrogen is also responsible for maintaining a differentiated epithelial morphology through an unknown mechanism.