Abstract
BackgroundThe importance of estrogen in regulation of fluid absorption and sperm maturation in the rodent epididymis has been established from studies on estrogen receptor-alpha knockout mice. However, functional studies on the role of estrogen in primate epididymis have been few. The main objective of this study was therefore to extend these observations and systematically analyze the presence and function of estrogen receptors in modulating the function of the primate epididymis, using the bonnet monkey (Macaca radiata) as a model system.MethodsA steroidal estrogen receptor (ER) antagonist, ICI 182780 (ICI), was administered to adult male bonnet monkeys via mini-osmotic pumps for a duration of 30 to 180 days. The expression of key estrogen-regulated genes (ER-alpha, Na-K ATPase alpha-1 and Aquaporin-1) was examined at specific time points. Further, the effect of ICI in modulating fluid reabsorption in efferent ductules was monitored, and critical sperm-maturation parameters were also analyzed.ResultsOur studies in the bonnet monkey revealed that both ER-alpha and ER-beta were expressed in all the three regions of the epididymis. We observed an increase in ER-alpha mRNA and protein in the caput of ICI-treated monkeys. Steady state mRNA levels of the water-channel protein, Aquaporin-1, was significantly lower in the caput of ICI-treated monkeys compared to controls, whereas the mRNA levels of Na-K ATPase alpha-1 remained unchanged. In vitro incubation of efferent ductules with ICI resulted in two-fold increase in tubular diameter, indicating affected fluid reabsorption capacity. Furthermore, sperm from ICI-treated monkeys were immotile.ConclusionTaken together, our results point to an integral role for estrogen in modulating the functions of the bonnet monkey epididymis. This study also demonstrates possible differences in the epididymal physiology of rodents and non-human primates, and thus underscores the significance of reports such as these, that examine the physiology of non-human primates (as opposed to rodents), in an attempt to understand similar events in the human.
Highlights
The importance of estrogen in regulation of fluid absorption and sperm maturation in the rodent epididymis has been established from studies on estrogen receptor-alpha knockout mice
RT-PCR analysis for ERα, AQP-1 and Na+-K+ ATPase-α1 in the three regions of the epididymis In order to ascertain the presence of ERα in the bonnet monkey epididymis, RNA from the caput, corpus and cauda was subjected to RT-PCR analysis using specific primers
It has been well documented that the efferent ductules of rodents express components like AQP-1 and Na+-K+ ATPase, which are important for fluid absorption [3]
Summary
The importance of estrogen in regulation of fluid absorption and sperm maturation in the rodent epididymis has been established from studies on estrogen receptor-alpha knockout mice. The epididymis consists of tubules which form a conduit for spermatozoa traversing from the efferent ductules to the vas deferens. It is anatomically divided into three parts- the caput (the head), a narrow central portionthe corpus (the body) and the cauda (the tail). The epithelium lining of these tubules secretes ions and proteins, reabsorbs testicular fluid and creates a specialized luminal environment for the maturation of testicular spermatozoa [1]. These important functions of the efferent ductules and the epididymis are regulated by a complex interplay of growth factors and hormones
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