Pyriproxyfen induces intracellular calcium overload and alters antioxidant defenses in Danio rerio testis that may influence ongoing spermatogenesis.

We investigated the in vitro effects of pyriproxyfen on ionic balance in the testis of the zebrafish by measuring 45Ca2+ influx. In vivo pyriproxyfen treatment was carried out to study oxidative stress, and conduct morphological analysis of the testis and liver. Whole testes were incubated in vitro with/without pyriproxyfen (10-12, 10-9 or 10-6 M; 30 min) and 45Ca2+ influx determined. To study pyriproxyfen's mechanism of action, inhibitors/activators of ionic channels or pumps/exchangers, protein kinase inhibitors or a calcium chelator were added 15 min before the addition of 45Ca2+ and pyriproxyfen. We evaluated the in vivo effects of 7 day exposure to waterborne pyriproxyfen (10-9 M) on reactive oxygen species (ROS) formation, lipid peroxidation, and reduced glutathione content (GSH), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and γ-glutamyltransferase (GGT) activity. Morphological analyses of the testis and liver were carried out after in vivo exposure of D. rerio to pyriproxyfen. Pyriproxyfen increased 45Ca2+ influx by opening the voltage-dependent T-type channels (T-type VDCC), inhibiting sarco/endoplasmic reticulum 45Ca2+-ATPase (SERCA) and the NCX exchanger (forward mode) and by mobilizing calcium from stores. The involvement of potassium channels and protein kinase C (PKC) was also demonstrated in pyriproxyfen-induced intracellular calcium elevation. In vivo pyriproxyfen treatment of D. rerio increased lipid peroxidation, decreased GSH content and increased GST activity in testes, in addition to increasing the number and size of spermatogonia cysts and inducing hepatocyte basophilia and dilation of blood vessels in the liver. The toxicity of pyriproxyfen is mediated by calcium overload, increased lipid peroxidation, and a diminished antioxidant capacity in the testis, due to GSH depletion, and altered spermatogenesis. The development of high basophilia in the liver suggests that pyriproxyfen may have estrogenic activity, possibly acting as an endocrine-disruptor. These findings indicate that these alterations may contribute to pyriproxyfen toxicity and spermatogenesis disruption.

Effects of different doses of nandrolone decanoate on estrous cycle and ovarian tissue of rats after treatment and recovery periods.

This study tested the hypothesis that different doses of nandrolone decanoate (ND) will cause changes in the estrous cycle and ovarian tissue of adult rats; and investigated the duration of the recovery period that is sufficient to restore the damage in the animals treated with different doses. Wistar rats were treated with ND at doses of 1.87, 3.75, 7.5 and 15 mg/kg body weight, or received mineral oil (control group) for 15 days, subcutaneously. All animals were divided into three groups according to the treatment periods: (i) ND treatment for 15 days; (ii) ND treatment followed by a 30-day recovery; and (iii) ND treatment followed by a 60-day recovery. Estrous cycle was monitored daily, and at the end of each period, the animals were euthanized for histopathological analysis. During ND treatment and after 30-day recovery, all animals exhibited persistent diestrus. After a 60-day recovery, persistent diestrus was only maintained in the group that had received the highest dose. Ovarian weight was decreased significantly after the 30-day recovery, regardless of ND doses, compared with the control group. There was a reduction (P < 0.05) in the number of corpora lutea and antral and growing follicles, in contrast to an increase (P < 0.05) in atretic follicles in a dose- and time-dependent manner. Remarkable histopathological changes occurred in the ovaries of all ND-treated groups. In conclusion, the different doses of ND caused changes in the estrous cycle and ovarian tissue of rats, and recovery periods (30 and 60 days) were insufficient to completely restore the damage in the animals treated with the highest dose.

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.