5alpha-reductase 2 inhibition impairs brain defeminization of male rats: Reproductive aspects

The present study was carried out to determine whether 5alpha-reductase 2 (5alpha-R2) metabolic pathway plays a key role in brain sexual differentiation. The inhibition of 5alpha-R2 by finasteride (20 mg/kg/day) from gestational day 19 to postnatal day 5 has long-term effects on sexual behavior and reproductive physiology detected only in adult life. Sexual maturation assessed by timing of preputial separation was unchanged. Finasteride-treated males were able to mate with untreated females which became pregnant but exhibited increased rate of pre-implantation loss. The subfertility observed was probably due to abnormally shaped sperm, since the sperm number was not altered. While plasma testosterone was enhanced, LH levels were not changed. The copulatory potential was not affected and all finasteride-treated rats presented male sexual behavior. Despite this, 53% of them showed homosexual behavior when pretreated with estradiol, suggesting an incomplete brain defeminization. These results indicate that 5alpha-R2 acts in brain sexual differentiation of male rats. Moreover, we suggest that 5alpha-R2 not only produces essential metabolites that act together with estradiol in brain sexual differentiation but also protects the brain from the damaging effects of estradiol excess. (c) 2005 Elsevier B.V. All rights reserved.

Copulatory efficiency and fertility in male rats exposed perinatally to flutamide

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

Influence of different doses of retinoic acid on cardiac remodeling

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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)

Paternal treatment with cisplatin impairs reproduction of adult male offspring in rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

GH overexpression causes muscle hypertrophy independent from local IGF-I in a zebrafish transgenic model

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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 Gestational and Lactational Fenvalerate Exposure on Immune and Reproductive Systems of Male Rats

The aim of this study was to determine the consequent reproductive developmental and immunotoxic effects due to exposure to fenvalerate during pregnancy and lactation in male offspring of maternal-treated rats. Pregnant rats were treated daily by oral gavage with 40 or 80 mg/kg of fenvalerate or corn oil (vehicle, control), from d 12 of pregnancy to d 21 of lactation. Immune and reproductive developmental effects were assessed in male offspring at postnatal days (PND) 40 (peripuberty), 60 (postpuberty), and 90 (sexual maturity). Treatment with the higher dose (80 mg/kg) resulted in convulsive behavior, hyperexcitability, and mortality in 45% of the dams. Fenvalerate was detected in the fetus due to placental transfer, as well as in pups due to breast-milk ingestion, persisting in male offspring until PND 40 even though pesticide treatment was terminated on PND 20. However, fenvalerate did not produce marked alterations in age of testicular descent to the scrotum and prepucial separation, parameters indicative of puberty initiation. In contrast, at puberty, there was a reduction in testicular weight and sperm production in male offspring of maternal-treated rats. At adulthood, the sperm counts and fertility did not differ between control and treated groups. Testosterone levels were not changed at any time during reproductive development. Similarly, no apparent exposure-related effects were detected in the histological structures of the lymphohematopoietic system. Data indicate that fenvalerate, in this experimental model, interfered with initial development of the male reproductive system, but that these effects on sperm production or fertility did not persist into adulthood. There was no apparent evidence that fenvalerate altered testosterone levels or produced a disruption in male endocrine functions.

Developmental exposure to diuron causes splenotoxicity in male Sprague-Dawley rat pups

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

Assessment of Female Reproductive Endpoints in Sprague-Dawley Rats Developmentally Exposed to Diuron: Potential Ovary Toxicity

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

In utero protein restriction causes growth delay and alters sperm parameters in adult male rats

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

Developmental changes in cold tolerance and ability to autoresuscitate from hypothermic respiratory arrest are not linked in rats and hamsters

In adult mammals, severe hypothermia leads to respiratory and cardiac arrest, followed by death. Neonatal rats and hamsters can survive much lower body temperatures and, upon artificial rewarming, spontaneously recover from respiratory arrest (autoresuscitate), typically suffering no long-term effects. To determine developmental and species differences in cold tolerance (defined here as the temperature of respiratory arrest) and its relation to the ability to autoresuscitate, we cooled neonatal and juvenile Sprague-Dawley rats and Syrian hamsters until respiration ceased, followed by rewarming. Ventilation and heartbeat were continuously monitored. In rats, cold tolerance did not change throughout development, however the ability to autoresuscitate from hypothermic respiratory arrest did (lost between postnatal days, P, 14 and 20), suggesting that the mechanisms for maintaining breathing at low temperatures was retained throughout development while those initiating breathing on rewarming were altered. Hamsters, however, showed increased cold tolerance until P26-28 and were able to autoresuscitate into adulthood (provided the heart kept beating throughout respiratory arrest). Also, hamsters were more cold tolerant than rats. We saw no evidence of gasping to initiate breathing following respiratory arrest, contributing to the hypothesis that hypothermic respiratory arrest does not lead to anoxia. (C) 2012 Elsevier B.V. All rights reserved.

Respiratory rhythm of brainstem-spinal cord preparations: Effects of maturation, age, mass and oxygenation

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

Differentiation of Leydig Cells in the Mongolian Gerbil

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

Short-Term Antiandrogen Flutamide Treatment Causes Structural Alterations in Somatic Cells Associated with Premature Detachment of Spermatids in the Testis of Pubertal and Adult Guinea Pigs

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