Copulatory efficiency and fertility in male rats exposed perinatally to flutamide

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

Reproductive effects in male rats exposed to diuron

Diuron is a ureic herbicide considered to have very low toxicity. The present study evaluated several aspects of reproductive toxicity of diuron in adult male rats. Diuron was diluted in corn oil and administered by oral gavage to groups of 18-20 rats at doses of 0, 125 or 250 mg/kg per day for 30 days; the control group received only the corn oil vehicle. At the end of the treatment period, approximately half the animals from each group were assigned to one of two terminal assessment lines: (1) reproductive organ, liver and kidney weights; measurement of diuron concentrations in liver and kidney; plasma testosterone determinations; evaluation of daily sperm production per testis; sperm number and sperm transit time in the epididymis; or (2) sexual behavior assessment during cohabitation with a receptive female; fertility and pregnancy outcome after natural mating; testicular, epididymal, kidney and liver histopathology; sperm morphology. After 30 days of oral diuron treatment, there were no treatment-related changes in body weights, but dose-related diuron residues were detected in the liver of all treated rats and absolute and relative liver weights were increased in both groups. There were no statistically significant differences between the treated and control groups obtained in plasma testosterone concentrations, or in parameters of daily sperm production, sperm reserves in the epididymis, sperm morphology or measured components of male sexual behavior. on the other hand, the number of fetuses in the litters from diuron-treated rats was slightly smaller than litters from control rats. Therefore, although the results did not indicate that diuron exposure resulted in direct male reproductive toxicity in the rat, they suggest that additional studies should be undertaken to investigate the possible effects on fertility and reproductive performance. (c) 2006 Elsevier B.V. All rights reserved.

Fertility of rat epididymal sperm after chemically and surgically induced sympathectomy

Guanethidine, a chemical that selectively blocks sympathetic noradrenergic neurons, was used to investigate the role of sympathetic innervation in the fertility of rat epididymal sperm, using both natural mating and in utero insemination protocols. This animal model correlates, at least in part, with spinal cord injury (SCI) in men. Adult male rats were treated daily by i.p. injections, for 21 or 42 days, with 0 or 6.25 mg/kg guanethidine. To compare the effects of guanethidine-induced sympathectomy with those following surgically induced sympathectomy, the inferior mesenteric ganglion and the proximal hypogastric nerves were removed in another group of rats. Both chemically and surgically induced sympathectomy increased the weight of the epididymis and seminal vesicles/coagulating glands as well as the number and the transit time of cauda epididymal sperm. Neither serum testosterone levels nor LH was affected by treatment with guanethidine. Using natural mating, no litters were produced by guanethidine-treated rats. Chemically denervated rats failed to produce copulatory plugs or ejaculate into the uterus. However, distal cauda epididymal sperm from chemically or surgically denervated rats displayed normal fertilization ability (80%) using in utero inseminations. In addition, the sperm of denervated rats did not show abnormal sperm chromatin structure using an assay that detects DNA damage. We conclude that sympathectomy delays the transit of sperm through the cauda epididymidis and produces ejaculatory dysfunction but does not compromise sperm quality in the distal cauda epididymidis. Moreover, these data provide compelling evidence that there is no association between the prolonged transit time of sperm within the epididymis, i.e., pre-ejaculatory sperm aging, and the fertility of those sperm, which has important implications for artificial insemination using sperm from men with SCI.

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.

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.

Long-term effects of developmental exposure to di-n-butyl-phthalate (DBP) on rat prostate: Proliferative and inflammatory disorders and a possible role of androgens

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

Early Changes Induced by Short-Term Low-Dose Cadmium Exposure in Rat Ventral and Dorsolateral Prostates

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

Effects of methylmercury on male reproductive functions in Wistar rats

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

Lobe Variation Effects of Experimental Diabetes and Insulin Replacement on Rat Prostate

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

Persistent Impairment of Testicular Histology and Sperm Motility in Adult Rats Treated with Cisplatin at Peri-Puberty

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Chronic caffeine intake increases androgenic stimuli, epithelial cell proliferation and hyperplasia in rat ventral prostate

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

Prostate carcinogenesis induced by N-methyl-N-nitrosourea (mnu) in gerbils: Histopathological diagnosis and potential invasiveness mediated by extracellular matrix components

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

Functional and Morphological Reproductive Aspects in Male Rats Exposed to Di-n-Butyl Phthalate (DBP) in Utero and During Lactation

The potential adverse reproductive effects, with emphasis on the epididymis, of in utero and lactational exposure to 100 mg/kg/d di-n-butyl phthalate (DBP) in adult male rat offspring were investigated. The fetal testis histopathology was also determined. The selected endpoints included reproductive organ weights, sperm motility and morphology, sperm epididymal transit time, sperm quantity in the testis and epididymis, hormonal status, fetal testis and epididymal histopathology and stereology, and androgen receptor (AR), aquaporin 9 (AQP9), and Ki-67 immunoreactivities. Pregnant females were divided into two groups: control (C) and treated (T). The treated females received DBP (100 mg/kg/d, by gavage) from gestation day (GD) 12 to postnatal day (PND) 21, while control dams received the vehicle. Some pregnant dams were killed by decapitation on GD20, and testes from male fetuses were collected for histopathogy. Male rats from other dams were killed at PND 90. Fetal testes from treated group showed Leydig-cell clusters, presence of multinucleated germinative cells, and increase of the interstitial component. Testosterone levels and reproductive organ weights were similar between the treated and control adult groups. DBP treatment did not markedly affect relative proportions of epithelial, stromal, or luminal compartments in the epididymis; sperm counts in the testis and epididymis; sperm transit time; or sperm morphology and motility in adult rats. The AR and AQP9 immunoreactivities and proliferation index were similar for the two groups. These results showed that fetal testes were affected by DBP as evidenced by testicular histopathologic alterations, but reproductive parameters and epididymal structure/function were not significantly altered in the adult animals exposed to 100 mg/kg DBP in utero and during lactation.

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)