Acceleration of Sperm Transit Time and Reduction of Sperm Reserves in the Epididymis of Rats Exposed to Sibutramine

Sibutramine is a drug globally used for the treatment of obesity. The aim of this study was to investigate male reproductive disorders caused by sibutramine in adult rats. Wistar rats were treated for 28 consecutive days (gavage) with 10 mg/kg of sibutramine. Control animals received only vehicle (dimethylsulfoxide and saline). The rats were sacrificed for evaluation of body and reproductive organ weights, sperm parameters, hormone levels (luteinizing hormone, follicle-stimulating hormone, and testosterone), testicular and epididymal histopathology, sexual behavior, fertility and in vitro contractility of the epididymal duct. Sibutramine decreased (P < .05) weights of the epididymis and ventral prostate, but not of other reproductive organs. The sperm number and transit time in the epididymal cauda were decreased (P < .001), but the daily sperm production was not altered. Moreover, morphology and sperm motility, histopathology of the testes and epididymis, sexual behavior, fertility, and serum hormone levels were not altered by the treatment. Sibutramine increased the potency of norepinephrine and, per se, increased the mechanical activity of the epididymal duct in vitro. Thus, although sibutramine in these experimental conditions did not interfere with the reproductive process of rats, it provoked acceleration of the sperm transit time and a decrease in the sperm reserves in the epididymal cauda. This alteration is probably related to the sympathomimetic effect of this drug, as shown by the in vitro assays. In humans, use of this drug might present a threat for male fertility because sperm reserves in men are naturally lower than those in rats.

Effects of altered epididymal sperm transit time on sperm quality

The epididymal sperm transit time seems to have an important role in the process of sperm maturation, and it seems that alterations to the transit can harm the process. The aim of the present work was to evaluate the influence of altered sperm transit time through the epididymis on sperm parameters and fertility of rats, as well as the role of testosterone in the alterations. Sprague-Dawley adult male rats were randomly assigned to four different groups and were treated for 12 days: (i) 10 mu g/rat/day DES, to accelerate the transit; (ii) 6.25 mg/kg/day guanethidine sulphate, to delay the transit; (iii) same treatment as group 1, plus androgen supplementation; (iv) control animals received the vehicles. Guanethidine treatment delayed the sperm transit time through the epididymal cauda, provoking increased sperm reserves in this region. Animals exposed to DES showed an acceleration of sperm transit time in the epididymis, and consequently decreased sperm density in both epididymal regions, the caput-corpus and cauda, and diminished sperm motility. In both cases sperm production was not altered. Testosterone supplementation was able to restore the transit time to values close to normality, as they were higher than in the control rats. The same occurred in relation to sperm motility. Rats exposed to DES presented lower fertility after in utero artificial insemination using sperm collected from the proximal cauda epididymis. Therefore, it was concluded that the acceleration of rat sperm transit time appeared to harm normal sperm maturation, thus decreasing sperm quality and fertility capacity, in an androgen-dependent way.

Orchidopexy restores morphometric-stereologic changes in the caput epididymis and daily sperm production in cryptorchidic mice, although sperm transit time and fertility parameters remain impaired

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Bupropion treatment increases epididymal contractility and impairs sperm quality with no effects on the epididymal sperm transit time of male rats

Bupropion is a dopamine (DA) and norepinephrine (NE) reuptake inhibitor used as smoking cessation and antidepressant drug with a lower incidence of male sexual dysfunction. We showed previously that sibutramine, a norepinephrine/serotonine reuptake inhibitor, reduced male rat fertility. As there are no studies evaluating the impact of bupropion treatment on spermatic parameters and male fertility, we evaluated the effects of bupropion treatment (15 and 30 mg kg(-1), 30 days) on sexual behavior, spermatic parameters and fertility of male Wistar rats and on the epididymal duct in vitro contractility. Bupropion 15 mg kg(-1) increased the serum luteinizing hormone level and the epididymal duct contractility, but the sperm quality was not affected. At 30 mg kg(-1) bupropion impaired sperm quality increasing the incidence of non-progressive sperm. The male sexual behavior and fertility were not modified at both bupropion doses. These results, in rats, suggest the importance of studies evaluating the effects of bupropion on the human male sperm quality.

Glutamate-induced obesity leads to decreased sperm reserves and acceleration of transit time in the epididymis of adult male rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Rat epididymal sperm quantity, quality, and transit time after guanethidine-induced sympathectomy

Guanethidine, a chemical that selectively abolishes peripheral noradrenergic nerves, was used to investigate the role of sympathetic innervation in the maintenance of epididymal sperm quantity and quality. Four groups of 10 adult male rats each were treated daily for 21 days, by i.p. injections, with either 0 (saline vehicle), 6.25, 12.5, or 25 mg/kg guanethidine. Norepinephrine content was reduced to undetectable levels in the cauda epididymidis in all guanethidine groups after 3 wk of treatment and was reduced to 7.4% of the control values after 1 wk of 6.25 mg/kg treatment. While body weight gain was significantly decreased at 12.5 and 25 mg/kg compared to that in controls, there was a significant increase in the weights of the seminal vesicles/coagulating glands in all treated groups. The number of homogenization-resistant spermatids per testis and the daily sperm production per testis remained unchanged. The weight of the epididymis was significantly increased at 6.25 and 12.5 mg/kg. Moreover, the number of cauda epididymal sperm and the transit time were increased significantly at 6.25 mg/kg (10.2 days) compared to values in the control cauda (6.3 days). Neither serum testosterone levels nor LH was affected in a dosage-related manner. There were no effects of guanethidine treatment on cauda epididymal sperm motility or morphology. A quantitative analysis of detergent-extracted cauda epididymal sperm proteins by SDS-PAGE revealed no differences, but there were diminutions in seven proteins in homogenates of caput/ corpus tissue. Histologic analysis of testis and epididymis sections revealed no differences between control and denervated animals. In a subsequent experiment the lowest effective dosage (6.25 mg/kg) was given to rats for 1 wk, and an increased number of cauda epididymal sperm and a delay in sperm transit were observed. Our results indicate that low-dosage guanethidine exposure denervates the epididymis within 1 wk, thereby delaying epididymal transit; however, neither 1- nor 3-wk exposure produces qualitative changes in the sperm.

Gastro-intestinal transit time in South American deer

The study of diet and physiological peculiarities of the digestive system of neotropical deer is not well known and the literature shows inconsistencies. To better understand the digestive system of these mammals the difference in the gastro-intestinal transit time of four species of neotropical deer (Mazama americana, Mazama gouazoubira, Mazama nana, Blastocerus dichotomus), kept ill captivity, was evaluated. Four plants (Neonotonia wightii, Morus albans, Medicago sativa, Leucaena leucocephala) were utilized and two variables were measured, mean time of the beginning of the elimination (BE) and mean time of permanence (TP). The results obtained for BE indicated similarity among the deer species, with significant differences between M. gouazoubira (mean = 13.62 hr) and M. Americana (mean = 19.25 hr). For the plants, the BE was faster with N. wightii and L. leucocephala, and slower for M. sativa. The TP results for B. dichotomus showed longer time when compared to the other species, whereas M. gouazoubira had a lower permanence. Overall, N. wightii had the highest retention time in the digestive tract of all the deer species studied. Associated with this observation, N. wightii had the highest quantity of plant fiber of the plants tested. In a similar fashion M. sativa showed the lowest TP in the digestive tract of the deer and had the lowest quantity of acid detergent fiber. The data from this study showed that, within species, the shape of the excretion curve of the plants was similar when the animals consumed N. wightii or M. sativa. Blastocerus dichotomus and M. gouazoubira had the highest and the lowest gastro-intestinal transit time, respectively. This suggests that these species characterize different abilities to digest high fiber food, and consequently, represent the two extremities in the morphophysiological adaptation within the deer species evaluated. This information is vital because it is important to know the digestive physiology to define the diet of captive animals, particularly regarding the quantity and quality of fiber. Zoo Biol 25:47-57, 2006. (C) 2005 Wiley-Liss, Inc.

Decreased Sperm Motility in Rats Orally Exposed to Single or Mixed Pesticides

The Brazilian Agency of Sanitary Vigilance (ANVISA) conducted a study that demonstrated the presence of residues of several pesticides in fresh fruits and vegetables that were available for purchase by the general populace. In order to evaluate potential adverse health effects of low-level exposure to agrochemicals, the reproductive toxicity of the pesticides dicofol, dichlorvos, permethrin, endosulfan, and dieldrin was evaluated in rats dosed with these chemicals individually or as mixtures. Sixty male Lewis rats (6 wk old, 200 x g) were randomly allocated to 8 groups: (1) control group, received basal diet; (2) 5 groups designated a to e received the diet containing each pesticide individually, at the respective effective doses: lowest-observed-adverse-effect level (LOAEL) for dieldrin and endosulfan, lowest-observed-effect level (LOEL) for dicofol, and lowest effect level (LEL) for dichlorvos and permethrin, respectively, depending on the published data; (3) effective dose group, which received a mixture of pesticides added to basal diet at the respective doses reported to produce adverse effects; and (4) low dose group, which received a pesticide mixture added to the basal diet, where each pesticide was at its no-observed-effect level (NOEL). After 8 wk of treatment, reproductive parameters were evaluated. Sperm morphology, daily sperm production (DSP), sperm transit time through the epididymis, hormonal levels, and histopathological evaluation of testis and epididymis did not differ significantly among the groups. However, sperm motility was significantly decreased in animals that received a mixture of dieldrin, endosulfan, dicofol, dichlorvos, and permethrin, as well as in the group receiving dicofol alone. Exposure to the individual pesticides endosulfan, dichlorvos, and permethrin did not markedly affect sperm motility. The impairment of sperm motility in the mixture of pesticides at the NOEL level indicates that reproductive effects not seen with individual pesticides may occur in presence of several pesticides due to an additive effect. However, the pesticide mixtures did not appear to affect DSP or spermatogenesis despite reduced sperm motility.

Sexual behaviour, sperm quantity and quality after short-term streptozotocin-induced hyperglycaemia in rats

Studies of diabetes mellitus in the streptozotocin rat model suggest that sexual dysfunctions may result from diabetes-induced alterations of the neuroendocrine-reproductive tract axis. Our investigation was performed to better define the effects of short-term hyperglycaemia on rat epididymal sperm quantity, quality and transit time, using both natural mating and artificial in utero insemination protocols. Male rats were made diabetic with streptozotocin (sc, 40 mg/kg), whereas controls received vehicle. Sexual behaviour was tested after 15 days and sperm fertilizing ability was checked 22 days after the injection through natural mating and artificial in utero insemination. Other parameters such as daily sperm production, testosterone levels, as well as sperm morphology and motility were also investigated. Fifty per cent of the diabetic animals showed no copulatory behaviour during tests and the number of animals reaching ejaculation was smaller in the diabetic group when compared with the control group (33% vs. 83%). Diabetes resulted in decreased body and reproductive organ weights, as well as diminished sperm counts in the testis and epididymis, that were associated with diminution of plasmatic testosterone levels. After natural mating, there was a decrease in the fertility in the diabetic adult male rats (25.5%) compared with control animals (81.5%). However, distal cauda epididymal sperm from diabetic rats displayed normal fertilization ability (91.5%) using in utero insemination. There were no effects of hyperglycaemia on sperm transit time in the epididymis and on spermatogenesis. Our results indicate that diabetes mellitus produces reproductive dysfunction, but does not compromise sperm fertilizing ability in the cauda epididymis in this experimental model.

Impairment on sperm quality and fertility of adult rats after antiandrogen exposure during prepuberty

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Pharyngeal clearance and pharyngeal transit time determined by a biomagnetic method in normal humans

Clearance and transit time are parameters of great value in studies of digestive transit. Such parameters are nowadays obtained by means of scintigraphy and videofluoroscopy, with each technique having advantages and disadvantages. In this study we present a new, noninvasive method to study swallowing pharyngeal clearance (PC) and pharyngeal transit time (PTT). This new method is based on variations of magnetic flux produced by a magnetic bolus passing through the pharynx and detected by an AC biosusceptometer (ACB). These measurements may be performed in a simple way. cause no discomfort. and do not use radiation. We measured PC in 8 volunteers (7 males and I female. 23-33 years old) and PTT in 8 other volunteers (7 males and I female. 21-29 years old). PC was 0.82 +/- 0.10 s (mean +/- SD) and PTT was 0.75 +/- 0.03 s. The results were similar for PC but longer for PTT than those determined by means of other techniques. We conclude that the biomagnetic method can be used to evaluate PC and PTT.