Delayed onset of puberty in male offspring from bisphenol A-treated dams is followed by the modulation of gene expression in the hypothalamic-pituitary-testis axis in adulthood.

Bisphenol A (BPA) is a synthetic endocrine-disrupting chemical of high prevalence in the environment, which may affect the function of the hypothalamic-pituitary-testis (HPT) axis in adult rats. The aim of the present study was to evaluate whether exposure to BPA during hypothalamic sexual differentiation at doses below the reproductive no observable adverse effect level of the World Health Organization causes changes in the regulation of the HPT axis. For this, 0.5 or 5mgkg-1 BPA was injected subcutaneously to the mothers from gestational day 18 to postnatal day (PND) 5. In adulthood (PND90), the mRNA expression of genes related to HPT axis was evaluated in hypothalamus, pituitary and testis. Hypothalamic expression of gonadotrophin-releasing hormone (Gnrh) and estrogen receptor 2 (Esr2) mRNA was increased in both BPA-treated groups compared to control group. In the pituitary, follicle stimulating hormone beta subunit (Fshb) and androgen receptor (Ar) mRNA expression was increased compared to control group in rats treated with 0.5mgkg-1 of BPA, whereas estrogen receptor 1 (Esr1) mRNA expression was only increased in the group treated with 5mgkg-1of BPA, compared to control group. In the testis, there was increased expression of FSH receptor (Fshr) and inhibin beta B subunit (Inhbb) transcripts only in rats treated with 0.5mgkg-1 of BPA. Serum testosterone and LH concentrations were increased in the group treated with 5mgkg-1of BPA. The results of the present study demonstrate for the first time that perinatal exposure to low doses of BPA during the critical period of hypothalamic sexual differentiation modifies the activity of the HPT axis in the offspring, with consequences for later life in adult rats.

Acrylamide: A review about its toxic effects in the light of Developmental Origin of Health and Disease (DOHaD) concept.

The endocrine system is highly sensitive to endocrine-disrupting chemicals (EDC) which interfere with metabolism, growth and reproduction throughout different periods of life, especially in the embryonic and pubertal stages, in which gene reprogramming may be associated with impaired development and control of tissues/organs even in adulthood. Acrylamide is considered a potential EDC and its main source comes from fried, baked and roasted foods that are widely consumed by children, teenagers and adults around the world. This review aimed to present some aspects regarding the acrylamide formation, its toxicokinetics, the occurrence of acrylamide in foods, the recent findings about its effects on different systems and the consequences for the human healthy. The challenges to characterize the molecular mechanisms triggered by acrylamide and to establish safe levels of consumption and/or exposure are also discussed in the present review.

Lipopolysaccharide and lipotheicoic acid differentially modulate epididymal cytokine and chemokine profiles and sperm parameters in experimental acute epididymitis.

Bacterial infections are the most prevalent etiological factors of epididymitis, a commonly diagnosed inflammatory disease in the investigation of male infertility factors. The influence of early pathogenic mechanisms at play during bacterial epididymitis on reproductive outcomes is little understood. We report here that experimental epididymitis induced in rats by Gram-negative (LPS) and Gram-positive (LTA) bacterial products resulted in differential patterns of acute inflammation in the cauda epididymis. LPS elicited a strong inflammatory reaction, as reflected by upregulation of levels of mRNA for seven inflammatory mediators (Il1b, Tnf, Il6, Ifng, Il10, Nos2 and Nfkbia), and tissue concentration of six cytokines/chemokines (IL1A, IL1B, IL6, IL10, CXCL2 and CCL2) within the first 24 h post-treatment. Conversely, LTA induced downregulation of one (Nfkbia) and upregulation of six (Il1b, Il6, Nos2, Il4 Il10 and Ptgs1) inflammatory gene transcripts, whereas increased the tissue concentration of three cytokines/chemokines (IL10, CXCL2 and CCL2). The stronger acute inflammatory response induced by LPS correlated with a reduction of epididymal sperm count and transit time that occurred at 1, 7, and 15 days post-treatment. Our study provides evidence that early epididymal inflammatory signaling events to bacterial activators of innate immunity may contribute to the detrimental effects of epididymitis upon male fertility.

Dynamic changes in the spatio-temporal expression of the ß-defensin SPAG11C in the developing rat epididymis and its regulation by androgens.

Herein, we characterized the spatio-temporal expression, cellular distribution and regulation by androgens of the ß-defensin SPAG11C, the rat ortholog of the human SPAG11B isoform C, in the developing epididymis by using RT-PCR, in situ hybridization and immunohistochemistry. We observed that Spag11c mRNA was ubiquitously expressed in rat fetuses, but preferentially detected in male reproductive tissues at adulthood. SPAG11C (mRNA and protein) was prenatally mainly detected in the mesenchyme of the Wolffian duct, switching gradually after birth to a predominant localization in the epididymis epithelium during postnatal development. In the adult epididymis, smooth muscle and interstitial cells were also identified as sources of SPAG11C. Furthermore, SPAG11C was differentially immunolocalized on spermatozoa surface during their transit from testis throughout caput and cauda epididymis. Developmental and surgical castration studies suggested that androgens contribute to the epididymal cell type- and region-specific modulation of SPAG11C mRNA levels and immunolocalization. Together our findings provide novel insights into the potential role of ß-defensins in the epididymis.

Daily exposure to silver nanoparticles during prepubertal development decreases adult sperm and reproductive parameters.

As silver nanoparticles (AgNPs) have antimicrobial properties and potentiate the activity of some antibiotics, they are broadly used in both medical and nonmedical applications. In this study, prepubertal male Wistar rats were orally treated with 15 or 30 µg/kg/day AgNPs from postnatal day 23 (PND23) to PND58 and sacrificed at PND102. The acrosome integrity, plasma membrane integrity, mitochondrial activity and morphological alterations of the sperm were analyzed. Sexual partner preference, sexual behavior and the serum concentrations of FSH, LH, testosterone and estradiol were also recorded. The results were evaluated following the appropriate statistical analyses, and differences among the groups were considered significant when p < 0.05. AgNPs reduced the acrosome and plasma membrane integrities, reduced the mitochondrial activity and increased the abnormalities of the sperm in both treatment groups. AgNP exposure also delayed the onset of puberty, although no changes in body growth were observed in either treatment group. The animals did not show changes in sexual behavior or serum hormone concentrations. This study shows for the first time that prepubertal exposure to AgNPs causes alterations in adult sperm parameters. Importantly, the sperm appeared to be more sensitive to the toxic effects of AgNPs and demonstrated adverse effects following exposure to lower doses. Consequently, the effects of AgNPs on sperm should be considered in order to establish safety limits for the use of these particles.

Adult exposure to bisphenol A (BPA) in Wistar rats reduces sperm quality with disruption of the hypothalamic-pituitary-testicular axis.

Reproductive physiology involves complex biological processes that can be disrupted by exposure to environmental contaminants. The effects of bisphenol A (BPA) on spermatogenesis and sperm quality is still unclear. The objective of this study was to investigate the reproductive toxicity of BPA at dosages considered to be safe (5 or 25mg BPA/kg/day). We assessed multiple sperm parameters, the relative expression of genes involved in the central regulation of the hypothalamic-pituitary-testicular axis, and the serum concentrations of testosterone, estradiol, LH and FSH. BPA exposure reduced sperm production, reserves and transit time. Significant damage to the acrosomes and the plasma membrane with reduced mitochondrial activity and increased levels of defective spermatozoa may have compromised sperm function and caused faster movement through the epididymis. BPA exposure reduced the serum concentrations of testosterone, LH and FSH and increased the concentration of estradiol. The relative gene expression revealed an increase in gonadotropin releasing hormone receptor (Gnrhr), luteinizing hormone beta (Lhb), follicle stimulating hormone beta (Fshb), estrogen receptor beta (Esr2) and androgen receptor (Ar) transcripts in the pituitary and a reduction in estrogen receptor alpha (Esr1) transcripts in the hypothalamus. In this study, we demonstrated for the first time that adult male exposure to BPA caused a reduction in sperm production and specific functional parameters. The corresponding pattern of gene expression is indicative of an attempt by the pituitary to reestablish normal levels of LH, FSH and testosterone serum concentrations. In conclusion, these data suggest that at dosages previously considered nontoxic to reproductive function, BPA compromises the spermatozoa and disrupts the hypothalamic-pituitary-gonadal axis, causing a state of hypogonadotropic hypogonadism.

Efeitos in vivo de resina dental á base de metacrilato glicerolato (BISGMA) na Puberdade de ratos wistar / Nursing diagnosis in the post operative period of cardiac surgery

This study aimed to determine the effects of the application of sealant in dental element and its possible influence on the reproductive development and hormonal profile in male Wistar rats as experimental models. Thirty-two male Wistar rats were randomly allocated in four groups, from 23PND (Post Natal Day) to 53PND. They were treated with autopolymerizable or photopolymerizable dental sealant (BISGMA), estradiol cipionate (positive control) or saline solution (negative control). The effects were monitored by the body weight gain, serum concentration of testosterone and estradiol, and by the structure of the seminiferous tubules. Both dental sealants caused alterations in germinative epithelium of the seminiferous tubules, but they didn´t interfere in hormonal serum levels of testosterone or estradiol, neither in body development. It´s possible to conclude that the application of dental sealant in prepubertal period causes damages to the testicular structure, with reduction of the tubular epithelium.

O presente estudo teve como objetivos determinar os efeitos da aplicação de selante de cicatrículas e fissuras em elemento dentário sobre o desenvolvimento reprodutivo masculino pré-púbere e perfil hormonal. Utilizaram-se 32 ratos Wistar machos alocados em 4 grupos dos 23º aos 53º dias de idade e tratados com uma das duas formulações comerciais de selantes dentários à base de dimetacrilato (BISGMA), uma utopolimerizável e outro fotopolimerizável, um grupo com cipionato de estradiol (controle positivo) e outro com solução salina (controle negativo). As possíveis alterações foram avaliadas pelo ganho de peso corporal, concentração sérica de testosterona e estradiol e características estruturais dos testículos. Notou-se que a administração do selante nas suas duas formas, auto-polimerizável e foto-polimerizável, causou alteração no epitélio germinativo dos túbulos seminíferos, mas sem alterações nas concentrações hormonais de estradiol e testosterona. Com base nesse estudo, foi possível concluir que a administração de selantes dentários em ratos Wistar machos pré-púberes, acarreta danos ao epitélio dos túbulos seminíferos constatadas por mudanças na estrutura testicular com redução do epitélio tubular.