Low doses of bisphenol A can impair postnatal testicular development directly, without affecting hormonal or oxidative stress levels.

Bisphenol A (BPA) is considered a potent endocrine disruptor, causing changes in the endocrine system due to its oestrogenic activity. Male individuals may be susceptible to endocrine, morphological and physiological alterations during testicular postnatal development. The aim of the present study was to evaluate whether exposure to BPA during the peripubertal period can damage testicular development. To this end, male Wistar rats were treated with BPA via gavage at doses of 20 or 200µgkg-1 on Postnatal Days (PND) 36-66. The control group was treated with Oil+DMSO under the same conditions. On PND 67, rats were killed. The blood was collected for hormonal analysis, the testis for sperm count, oxidative stress, histopathological and immunohistochemical analyses for ki-67 and sperm of the vas deferens for morphological analysis. Both doses of BPA resulted in abnormal sperm morphology and seminiferous tubules, with the highest dose increasing the height of the germinal epithelium and reducing the number of spermatozoa at Stages IX-XIII of spermatogenesis. In conclusion, both doses of BPA administered during the peripubertal period impaired testicular development without any effects on hormone levels (luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone levels) or oxidative stress.

Exposure to aluminium chloride during the peripuberal period induces prostate damage in male rats.

Aluminium (Al) is an important metal, but it can be toxic including for prostate tissue. This study aimed to evaluate whether exposure to aluminium chloride (AlCl3) during the peripubertal period affects ventral prostate development in rats. Male Wistar rats (30 days old) were distributed into three experimental groups: control (sterile 0.9% saline solution), AL7 (7 mg AlCl3/kg) and AL34 (34 mg AlCl3/kg). Animals were treated intraperitoneally from postnatal day (PND) 36-66 (peripubertal period). At PND67, the animals were anaesthetized and euthanized. Blood was collected for testosterone levels. The ventral prostate (VP) was removed, weighed and processed for histochemistry and immunohistochemistry to detect androgen (AR) and Ki67. Stereological and histopathological analyses, mast cell counts, and determinations of myeloperoxidase (MPO) and N-acetyl glycosidase (NAG) activity and IL-6 levels were performed. The AL34 group presented a reduction in body weight and increase in MPO activity compared to the other groups. In both the AL7 and AL34 groups, there was reorganization of the prostatic tissue compartments. There was no significant difference in prostate weight, number of granulated or degranulated mast cells, or testosterone levels. In conclusion, the exposure to aluminium chloride during the peripubertal period impairs the prostatic development.

Maternal hypoxia developmentally programs low podocyte endowment in male, but not female offspring.

Fetal hypoxia is a common complication of pregnancy. We have previously reported that maternal hypoxia in late gestation in mice gives rise to male offspring with reduced nephron number, while females have normal nephron number. Male offspring later develop proteinuria and renal pathology, including glomerular pathology, whereas female offspring are unaffected. Given the central role of podocyte depletion in glomerular and renal pathology, we examined whether maternal hypoxia resulted in low podocyte endowment in offspring. Pregnant CD1 mice were allocated at embryonic day 14.5 to normoxic (21% oxygen) or hypoxic (12% oxygen) conditions. At postnatal day 21, kidneys from mice were immersion fixed, and one mid-hilar slice per kidney was immunostained with antibodies directed against p57 and synaptopodin for podocyte identification. Slices were cleared and imaged with a multiphoton microscope for podometric analysis. Male hypoxic offspring had significantly lower birth weight, nephron number, and podocyte endowment than normoxic male offspring (podocyte number; normoxic 62.86 ± 2.26 podocytes per glomerulus, hypoxic 53.38 ± 2.25; p < .01, mean ± SEM). In contrast, hypoxic female offspring had low birth weight but their nephron and podocyte endowment was the same as normoxic female offspring (podocyte number; normoxic 62.38 ± 1.86 podocytes per glomerulus, hypoxic 61.81 ± 1.80; p = .88). To the best of our knowledge, this is the first report of developmentally programmed low podocyte endowment. Given the well-known association between podocyte depletion in adulthood and glomerular pathology, we postulate that podocyte endowment may place offspring at risk of renal disease in adulthood, and explain the greater vulnerability of male offspring.

A High Fat Diet during Adolescence in Male Rats Negatively Programs Reproductive and Metabolic Function Which Is Partially Ameliorated by Exercise.

An interaction between obesity, impaired glucose metabolism and sperm function in adults has been observed but it is not known whether exposure to a diet high in fat during the peri-pubertal period can have longstanding programmed effects on reproductive function and gonadal structure. This study examined metabolic and reproductive function in obese rats programmed by exposure to a high fat (HF) diet during adolescence. The effect of physical training (Ex) in ameliorating this phenotype was also assessed. Thirty-day-old male Wistar rats were fed a HF diet (35% lard w/w) for 30 days then subsequently fed a normal fat diet (NF) for a 40-day recovery period. Control animals were fed a NF diet throughout life. At 70 days of life, animals started a low frequency moderate exercise training that lasted 30 days. Control animals remained sedentary (Se). At 100 days of life, biometric, metabolic and reproductive parameters were evaluated. Animals exposed to HF diet showed greater body weight, glucose intolerance, increased fat tissue deposition, reduced VO2max and reduced energy expenditure. Consumption of the HF diet led to an increase in the number of abnormal seminiferous tubule and a reduction in seminiferous epithelium height and seminiferous tubular diameter, which was reversed by moderate exercise. Compared with the NF-Se group, a high fat diet decreased the number of seminiferous tubules in stages VII-VIII and the NF-Ex group showed an increase in stages XI-XIII. HF-Se and NF-Ex animals showed a decreased number of spermatozoa in the cauda epididymis compared with animals from the NF-Se group. Animals exposed to both treatments (HF and Ex) were similar to all the other groups, thus these alterations induced by HF or Ex alone were partially prevented. Physical training reduced fat pad deposition and restored altered reproductive parameters. HF diet consumption during the peri-pubertal period induces long-term changes on metabolism and the reproductive system, but moderate and low frequency physical training is able to recover adipose tissue deposition and reproductive system alterations induced by high fat diet. This study highlights the importance of a balanced diet and continued physical activity during adolescence, with regard to metabolic and reproductive health.

Spermatic and testicular damages in rats exposed to ethanol: influence of lipid peroxidation but not testosterone.

Chronic consumption of ethanol causes morphological and physiological changes in the reproductive system of mammals. Vitamin C has an antioxidant role in organisms by neutralizing the ROS (reactive oxygen species) produced by oxidizing agents and this vitamin has an important function in the male reproductive system. The aim of this study was to evaluate whether vitamin C could prevent or attenuate the alterations in the male reproductive system caused by ethanol consumption. To test this hypothesis, male rats were divided into three experimental groups and treated by gavage for 63 days. The ethanol (E) and ethanol+vitamin C (EC) groups received 2 g/kg of ethanol (25%v/v) daily. In addition to ethanol, the EC group received vitamin C at a dose of 100 mg/day, diluted in water. The control group (C) received only the vehicle. On the 64th experimental day, the animals were anesthetized and euthanized, and blood was collected for plasmatic hormonal analysis. The testis, epididymis, vas deferens, and seminal vesicles were removed and weighed. Sperm from the vas deferens was submitted to morphological and motility analysis. The testis and epididymis were used for oxidative stress and histopathological analysis, sperm count, morphometric analysis of the testis, and stereological analysis of the epididymis. The results showed that vitamin C has a protective effect in the testes of adult male rats, entirely normalizing the parameters of sperm count, spermatogenesis kinetics, lipid peroxidation levels, and sperm motility, as well as partially normalizing the histopathological damage in the testis, epididymis, and sperm morphology. Thus, we concluded that lipid peroxidation is a major mechanism by which ethanol affects the testes and sperm, whereas no plasmatic testosterone alterations were found.