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Abstract Background Carbamazepine (CBZ) is a first-line antiepileptic drug (AED), although it is also used for the treatments of psychiatric disorders and neuropathic pain. The CBZ utilization has been associated with male reproductive damage, including hormonal alterations, sexual dysfunction and reduction of sperm quality. The wide and long-term use of the CBZ is a common schedule in children and adolescents and alters the testosterone level in adult rats and humans. The objective of this work was to evaluate the CBZ side effects on the ventral prostate of rats from pre-puberty to sexual maturation, since the prostate is an androgen-dependent organ. Methods Twenty three day-old male albino Wistar rats received CBZ diluted in propylene glycol (20 mg/Kg/i.p via). The treatment lasted 20, 40 and 70 days, according to the different stages of the rat sexual maturation. At the end of each treatment period, ventral prostates were removed and histologically processed. The prostate sections were submitted to the histopathological, morphological and stereological analyses using image analysis system. Results Reductions of the glandular epithelium, glandular lumen and fibromuscular stroma volume of the ventral prostate were observed in adult rats treated with CBZ since the weaning. Triggering and degranulation of mast cells were observed in the fibromuscular stroma of prepubertal and pubertal CBZ treated rats. Conclusions The results suggest a direct effect of the CBZ on rat ventral prostate, evidenced by increase of mast cell and macrophage populations during pre-puberty and puberty causing a ventral prostate accentuated damage in the adult phase.

Carcinogenesis is frequently linked to genetic background, however, exposure to environmental risk factors has gained attention as the etiologic agent for several types of cancer, including prostate. The intrauterine microenvironment has been described as a preponderant factor for offspring health; and maternal exposure to insult has been linked to chronic disease in older offspring. Using a model of maternal exposure to low-protein diet (LPD; 6% protein), we demonstrated that impairment of offspring rat prostatic growth on postnatal day (PND) 21 was associated with prostate carcinogenesis in older offspring (PND 540). One explanation is that maternal LPD consumption exposed offspring to an estrogenic intrauterine microenvironment, which potentially sensitized prostate cells early during glandular morphogenesis, increasing cellular response to estrogen in older rats. The onset of accelerated prostatic growth, observed on PND 21, associated with an unbalanced estrogen/testosterone ratio and increased circulating IGF-1 in older offspring appears to contribute to the development of prostate carcinoma in groups on gestational low protein and gestational and lactational low protein diets (33 and 50%, respectively). Our study strongly indicated maternal exposure to LPD as a potential risk factor for induction of slow-growing prostate carcinogenesis in rat offspring later in life. [ABSTRACT FROM AUTHOR]

ABSTRACT In the present study, it was evaluated the susceptibility of prostatic lesions in male adult rats exposed to Di- N-butyl-phthalate during fetal and lactational periods and submitted to MNU plus testosterone carcinogenesis protocol. Pregnant females were distributed into four experimental groups: CN (negative control); CMNU (MNU control); TDBP100 (100 mg/kg of DBP); TDBP500 (500 mg/kg of DBP). Females from the TDBP groups received DBP, by gavage, from gestation day 15 (GD15) to postnatal day 21 (DPN21), while C animals received the vehicle (corn oil). CMNU, TDBP100, and TDBP500 groups received a single intraperitoneal injection of MNU (50 mg/kg) on the sixth postnatal week. After that, testosterone cypionate was administered subcutaneously two times a week (2 mg/kg) for 24 weeks. The animals were euthanized on PND220. Distal segment fragments of the ventral (VP) and dorsolateral prostate (DLP) were fixed and processed for histopathological analysis. Protein extracts from ventral prostate were obtained, and western blotting was performed to AR, ERα, MAPK (ERK1/2), and pan-AKT. Stereological analysis showed an increase in the epithelial compartment in TDBP100 and TDBP500 compared to CN. In general, there was increase in the incidence of inflammation and metaplasia/dysplasia in the DBP-treated groups, mainly in DLP, compared to CN and CMNU. Proliferation index was significant higher in TDBP500 and PIN (prostatic intraepithelial neoplasia) was more frequent in this group compared to CMNU. Western blot assays showed an increase in the expressions of AR and MAPK (ERK1/2) in the TDBP100 compared to CN, and ERα and AKT expressions were higher in the TDBP500 group compared do CN. These results showed that different doses of DBP during prostate organogenesis in Wistar rats could increase the incidence of premalignant lesions in initiated rats inducing distinct biological responses in the adulthood. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1185-1195, 2016. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) has increased in recent years. Although the cellular and molecular mechanisms involved in GDM-increased risk factors to offspring remained poorly understood, some studies suggested an association between an increase in oxidative stress induced by maternal hyperglycemia and complications for both mothers and newborns. Here, we investigated the impact of maternal hyperglycemia followed by maternal insulin replacement during lactation on the expression of antioxidant enzymes and mast cell number in offspring ventral prostate (VP) at puberty. Pregnant rats were divided into three groups: control (CT); streptozotocin-induced maternal hyperglycemia (MH); and MH plus maternal insulin replacement during lactation (MHI). Male offspring were euthanized at postnatal day (PND) 60 and the VP was removed and processed for histology and Western blotting analyses. Maternal hyperglycemia delayed prostate maturation, and increased mast cell number catalase (CAT), superoxide dismutase (SOD), glutatione-s-transferase (GST-pi), and cyclooxygenase-2 (Cox-2) expression in the offspring of hyperglycemic dams. Maternal insulin replacement restored VP structure, mast cell number and antioxidant protein expression, except for Cox-2, which remained higher in the MHI group. Thus, an increase in oxidative stress induced by intrauterine hyperglycemia impacts prostate development and maturation, which persists until puberty. The overall improvement of maternal metabolism after insulin administration contributes to the restoration of prostate antioxidant enzymes and secretory function. Taken together, our results highlighted that imbalanced physiological maternal-fetal interaction contributes to the impairment of reproductive performance of the offspring from diabetic mothers. Anat Rec, 300:291-299, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)