A Review of Sympathetic and Parasympathetic Innervation in the Structural and Functional Maintenance of the Male Gonad

The nervous system controls and coordinates the functions of all body systems, including the male reproductive system. The male gonad, responsible for spermatogenesis and steroidogenesis, receives autonomous sympathetic and parasympathetic innervation, having a great influence on the structural and functional integrity of this organ. The testis receives autonomic innervation primarily at the superior and inferior poles, specifically by the superior and inferior spermatic nerves. This nervous control is wired into all testicular cell populations such as contractile cells (myoid cells), germ cells, and steroidogenic cells. Many studies have also described the influence of autonomic innervation on Sertoli cell control. Thus, any possible interference of physical or chemical agents whose action is directly or indirectly linked to the nervous control of the testicle can result in changes and/or damage to male reproduction, with emphasis on testicular impairment. The present chapter consists of a review of data about the effects of physical or chemical alterations on the autonomous innervation and its repercussions on male gonad. For this, it is necessary to understand the general aspect of the nervous system and the male gonad morphology and innervation, as well as the action of drugs or any methods that promote changes in the communication between these two systems

Slimmer or Fertile? Pharmacological Mechanisms Involved in Reduced Sperm Quality and Fertility in Rats Exposed to the Anorexigen Sibutramine

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. © 2013 Borges et al.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

<i>In vivo</i> sibutramine administration increases the potency of prazosin-induced antagonism of epididymal tension to tyramine.

<p>Concentration-reponse curves to tyramine in the absence and presence of prazosin 10 nM (PZS) in the epididymal cauda from vehicle (<b>A</b>) and sibutramine (<b>B</b>) treated rats. Numbers under the arrows indicate the reduction in the potency of tyramine-induced tension of epididymal segments evaluated at 37% of maximal response of control curves of both groups. Data are mean ± SEM of tissues from 3 rats/group.</p

Fertility assessment after <i>in utero</i> artificial insemination.

1<p>Values expressed as median and interquartile intervals *p<0.05 (Mann- Whitney test).</p>2<p>Values expressed as mean±SEM. (Student's t- test).</p

Effects of <i>in vitro</i> sibutramine on basal tonus activity of distal epididymal duct.

<p><b>A</b>: Tension developed in 5 min in the absence and presence of increasing concentrations of sibutramine. The data are expressed as the mean±SEM. *p<0.05, **p<0.01 vs control (ANOVA followed by Dunnett test). <b>B:</b> Tension developed in 5 min in the presence of sibutramine 3 µM and nifedipine 300 nM. Data are expressed as the mean±SEM. **p<0.01 vs control (Student's t- test).</p

<i>In vivo</i> prostate tension to methoxamine and the tension increased to NE by acute sibutramine administration.

<p><b>A:</b> Dose-response curves to methoxamine in the ventral prostate before (open symbols) and after (closed symbols) intravenous sibutramine 5 mg.kg⁻¹ administration (n = 4 rats). <b>B:</b> Dose-response curves to NE in the ventral prostate before (open symbols) and after (closed symbols) intravenous sibutramine 5 mg.kg⁻¹ administration (n = 5 rats). <b>A–B:</b> The data are expressed as the mean±SEM. * p<0.05 versus tension developed by the same NE dose before sibutramine administration (Student's t- test).</p

<i>In vivo</i> sibutramine administration decreases the tyramine-induced tension of epididymal cauda duct.

<p><b>A:</b> Concentration-response curves to norepinephrine in control and sibutramine-treated rats in the absence (open symbols) and in the presence (closed symbols) of cocaine 6 µM. <b>B:</b> Concentration-response curves to tyramine in control and sibutramine-treated rats before concentration-response curve to exogenous norepinephrine. <b>C:</b> Concentration-response curves to tyramine in control and sibutramine-treated rats after concentration-response curve to exogenous norepinephrine. <b>A–C:</b> The data are expressed as mean±SEM. Values of pEC₅₀ were not different between curves (Student's t- test). <b>D:</b> Maximal response (Emax) to tyramine before and after concentration-response curve to norepinephrine (NE) between control and sibutramine-treated rats. The data are expressed as the mean±SEM. *p<0.05 vs control (Student's t- test).</p