Abstract
Sperm acquire motility and fertility capacity during epididymal transit, under the control of androgens and sympathetic innervations. It is already known that the acceleration of epididymal sperm transit time can lead to lower sperm quality. In a previous work we showed that rats exposed to the anorexigen sibutramine, a non-selective serotonin-norepinephrine reuptake inhibitor, presented faster sperm transit time, lower epididymal sperm reserves and potentiation of the tension of epididymal duct to norepinephrine exposed acutely in vitro to sibutramine. In the present work we aimed to further investigate pharmacological mechanisms involved in these alterations and the impact on rat sperm quality. For this, adult male Wistar rats were treated with sibutramine (10 mg/kg/day) or vehicle for 30 days. Sibutramine decreased final body, seminal vesicle, ventral prostate and epididymal weights, as well as sperm transit time in the epididymal cauda. On the contrary of the in vitro pharmacological assays, in which sibutramine was added directly to the bath containing strips of distal epididymal cauda, the ductal tension was not altered after in vivo sub-chronic exposure to sibutramine. However, there is pharmacological evidence that the endogenous epididymal norepinephrine reserves were reduced in these animals. It was also shown that the decrease in prostate weight can be related to increased tension developed of the gland, due to sibutramine sympathomimetic effects. In addition, our results showed reduced sperm quality after in utero artificial insemination, a more sensitive procedure to assess fertility in rodents. The epididymal norepinephrine depletion exerted by sibutramine, associated with decreases in sperm transit time, quantity and quality, leading to reduced fertility in this experimental model, reinforces the concerns about the possible impact on fertility of man taking sibutramine as well as other non-selective serotonin-norepinephrine reuptake inhibitors, especially considering the lower reproductive efficiency of humans compared to males of other species.
Highlights
The epididymis is an organ of the male reproductive tract formed by highly convoluted duct that connects the efferent ducts to the vas deferens and performs a variety of functions, including sperm transport, maturation, protection, concentration and storage [1]
The contractions of the epididymal cauda induced by norepinephrine (NE) released by sympathetic nerve stimulation occur via activation of a1- adrenoceptor (a1-AR) [7]
Experiment 1 At the end of the experiment, significant reduction in the body weight gain was observed in the sibutramine-treated group (215.9165.95 g) when compared with control group (18.3863.88 g), as well as reductions in the weights of the epididymis, ventral prostate and seminal vesicle (Figure 1A)
Summary
The epididymis is an organ of the male reproductive tract formed by highly convoluted duct that connects the efferent ducts to the vas deferens and performs a variety of functions, including sperm transport, maturation, protection, concentration and storage [1]. This organ plays an important role in the acquisition of progressive sperm motility and fertilizing ability. The contractions of the epididymal cauda induced by norepinephrine (NE) released by sympathetic nerve stimulation occur via activation of a1- adrenoceptor (a1-AR) [7] Another organ that receives sympathetic and parasympathetic autonomic innervation is the prostate. The sympathetic stimulation (noradrenergic), via activation of a1-AR, contracts the prostatic smooth muscle cells releasing prostatic secretions into the urethra [8]
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