Bisphenol S (BPS) has been introduced into the industry as a safer alternative to bisphenol A (BPA). However, the recent studies have reported a possible association between BPS and disturbed glucose ...homeostasis, indicating that it may be a risk factor for type 1 and type 2 diabetes mellitus, obesity, and gestational diabetes mellitus. Nevertheless, the role of BPS in glucose metabolism remains controversial. In this study, we investigated the glucose metabolism of male Wistar rats born from dams that were BPS‐exposed (groups: BPS‐L (0.05 mg/kg/day), BPS‐H (20 mg/kg/day)) during pregnancy and lactation. We observed that both BPS treated groups of animals presented a significant decrease in anogenital distance/weight1/3, as compared to control animals, although no alterations in testosterone levels were observed. Furthermore, the BPS‐L group presented a significant decrease in body weight from postnatal day (PND) 21 to adult stage. In addition, a significant increase in glucose tolerance, pancreatic β‐cell proliferation, the frequency of small islets, and the average β‐cell size at PND 36 was observed in this group. However, no changes in insulin serum levels and percentage of β‐cells were recorded. Furthermore, these changes were not preserved at the adult stage (PND 120). The results suggest that the administration of low doses of BPS during the perinatal period induced an estrogenic like effect, with males apparently becoming more female‐like in their responses to a glucose challenge.
•Associations between bisphenol exposure and BTB protein expression are controversial.•BPA high dose exposure is associated with negative expression of BTB proteins.•Non-monotonic dose response curve ...of bisphenols effect in ZO-1 protein expression was observed.•More studies with lower bisphenol concentrations are needed.
Bisphenols are a group of environmental endocrine-disrupting chemicals that produce alterations in the expression of intercellular junction proteins of the Blood-Testis Barrier (BTB) involved in spermatogenesis. The association between bisphenol exposure and BTB protein expression is controversial. Therefore, we performed this systematic review and meta-analysis to clarify bisphenol effects on Sertoli cell BTB protein expression in vitro. The Standardized Mean Difference (SMD) with a 95 % confidence interval (95 % CI) was used to evaluate the association between alterations in the BTB protein expression and bisphenol exposure in vitro. Six articles were included in the meta-analysis. Bisphenol-A (BPA) exposure at 200 μM was associated with significant decrease in BTB protein expression (SMD = −2.70, 95 %CI: −3.59, −1.80, p het = 0.46, p = <0.00001). In the moderate (40−50 μM) and low dose (<25 μM), no significant associations were obtained. We also found a non-monotonic dose-response curve of bisphenol effect in ZO-1 protein expression; low and high doses presented a significant decrease compared to control, while moderate dose presented no change. The current temporary Tolerable Daily Intake (tTDI) of BPA is 4 μg/kg bw/day. The 5–25 μM doses of BPA are equivalent to ∼1–5 mg/kg bw, respectively. Although the low dose group (<25 μM) assessed doses below the previous NOAEL value, these doses are above the current tTDI. Thus, it is necessary to conduct more studies with lower bisphenol concentrations to avoid underestimating the potential adverse effects of bisphenols at doses below tTDI.
Bisphenols such as bisphenol A (BPA), S (BPS), C (BPC), F (BPF), AF (BPAF), tetrabromobisphenol, nonylphenol, and octylphenol are plasticizers used worldwide to manufacture daily-use articles. ...Exposure to these compounds is related to many pathologies of public health importance, such as infertility. Using a protector compound against the reproductive toxicological effects of bisphenols is of scientific interest. Melatonin and vitamins have been tested, but the results are not conclusive. To this end, this systematic review and meta-analysis compared the response of reproductive variables to melatonin and vitamin administration as protectors against damage caused by bisphenols. We search for controlled studies of male rats exposed to bisphenols to induce alterations in reproduction, with at least one intervention group receiving melatonin or vitamins (B, C, or E). Also, molecular docking simulations were performed between the androgen (AR) and estrogen receptors (ER), melatonin, and vitamins. About 1234 records were initially found; finally, 13 studies were qualified for review and meta-analysis. Melatonin plus bisphenol improves sperm concentration and viability of sperm and increases testosterone serum levels compared with control groups; however, groups receiving vitamins plus bisphenols had lower sperm concentration, total testis weight, and testosterone serum levels than the control. In the docking analysis, vitamin E had the highest negative MolDock score, representing the best binding affinity with AR and ER, compared with other vitamins and melatonin in the docking. Our findings suggest that vitamins could act as an endocrine disruptor, and melatonin is most effective in protecting against the toxic effects of bisphenols.
•Significant decrease in implantation sites was observed in the B♀-B♂ group.•The B♀-B♂ group showed a decrease in talin apical/basal expression ratio in UEC.•The B♀-B♂ group showed a decrease in ...occluding apical expression in UEC.•The B♀-B♂ group showed a decrease in E-cadherin apical/lateral expression ratio in UEC.•The B♀-B♂ group showed a decrease in E-cadherin expression in the blastocyst.
The aim was to evaluate the effect of perinatal BPA exposure of one or both parents on the implantation index and expression of talin, occludin and E-cadherin in the uterine epithelial cells (UEC) of the offspring. Pregnant Wistar dams (F0) received BPA or vehicle from gestational day (GD) 6 to lactation day 21. F1 animals were mated forming four groups: Control dam-Control sire (C♀-C♂), BPA dam -Control sire (B♀-C♂), Control dam -BPA sire (C♀-B♂), BPA dam -BPA sire (B♀-B♂). F1 dams were sacrificed at GD 6. Significantly decreased number of implantation sites was observed in the B♀-B♂ group as compared to the C♀-C♂ group, which correlated with decreased talin apical/basal expression ratio, occludin apical expression, and E-cadherin apical/lateral expression ratio in the UEC. Furthermore, decreased E-cadherin expression in the blastocyst was observed. Our data suggest that reduced protein expressions in F1 BPA offspring could result from decreased progesterone serum levels.
Serotonin (5-hydroxytryptamine; C(10)H(12)N(2)O (5-HT)) is produced in the CNS and in some cells of peripheral tissues. In the mammalian male reproductive system, both 5-HT and tryptophan hydroxylase ...(TPH) have been described in Leydig cells of the testis and in principal cells of the caput epididymis. In capacitated hamster sperm, it has been shown that 5-HT promotes the acrosomal reaction. The aim of this work was to explore the existence of components of the serotoninergic system and their relevance in human sperm physiology. We used both immunocytochemistry and western blot to detect serotoninergic markers such as 5-HT, TPH1, MAO(A), 5-HT(1B), 5-HT(3), and 5HT(T); HPLC for TPH enzymatic activity; Computer Assisted Semen Analysis assays to measure sperm motility parameters and pharmacological approaches to show the effect of 5-HT in sperm motility and tyrosine phosphorylation was assessed by western blot. We found the presence of serotoninergic markers (5-HT, TPH1, MAO(A), 5-HT(1B), 5-HT(2A), 5-HT(3), 5-HT(T), and TPH enzymatic activity) in human sperm. In addition, we observed a significant increase in tyrosine phosphorylation and changes in sperm motility after 5-HT treatment. In conclusion, our data demonstrate the existence of components of a serotoninergic system in human sperm and support the notion for a functional role of 5-HT in mammalian sperm physiology, which can be modulated pharmacologically.
▶ BPA administered to dams induce irregular estrous cycle of the offspring. ▶ BPA induces changes in uterine morphology and apoptosis pattern of the offspring. ▶ BPA induces a down regulation of ERα ...in uterine epithelial cells of the offspring. ▶ BPA administered chronically to dams modifies the reproductive cycle of the offspring.
Bisphenol A (BPA) is an estrogenic agonist compound that induces changes in diverse reproductive parameters in rats. The aim of the present study was to determine the effects of BPA given in drinking water containing 10
mg/L (approximate dose 1.2
mg/kg BW/day), administered chronically to rats during pregnancy and lactation, on reproductive tract parameters of the offspring. 79.2% of the female offspring from BPA-treated mothers presented irregular estrous cycles. As compared to the control group, a significant increase in the thickness of the uterine epithelia and stroma was observed in the BPA group. Additionally, 60% of the female offspring from BPA mothers did not undergo abundant uterine epithelial apoptosis during the estrus phase of the cycle while control animals did. In addition, a down regulation of ERα expression was observed in epithelial cells on estrus day. The results indicate that BPA, when administered chronically in water beverages to dams, modifies the reproductive cycle of the offspring during young adulthood.
Oral exposure to synthetic and natural endocrine disruptors (ED) at different stages of life is related to alterations in the reproductive system. Ruminants represent a model for studying the effects ...of ED in humans due to some similarities in their development. Ruminants are considered of great importance due to continuous exposure to pasture and contaminated soils and human consumption of their meat. The present review aims to describe ED effects in ruminants’ reproduction, when they are consumed in the perinatal, postnatal-pre-adulthood, and adult stages. Feeding with phytoestrogens (PE) rich forage has no nocive consequences on the male reproductive system at any stages of life; in females, they produce more significant harmful effects when administered in adulthood. In the perinatal and postnatal-pre-adulthood stages, negative effects of synthetic ED were found in both males and females. This review presents study opportunities for further research related to oral exposure to ED.
La exposición oral a disruptores endocrinos (DE) sintéticos y naturales en las distintas etapas de la vida está relacionada con alteraciones en el sistema reproductivo. Los rumiantes representan modelos adecuados para estudiar el impacto de los DE en los humanos por algunas similitudes en su desarrollo, se consideran de gran importancia por la exposición continua a pastura y suelo contaminado, y por el consumo humano de su carne. El objetivo de la presente revisión es describir los efectos producidos por consumir DE en etapa perinatal, posnatal-preadultez y adultez en rumiantes. La alimentación con forraje rico en fitoestrógenos (FE), no tiene efectos nocivos sobre la reproducción de machos en ninguna etapa de la vida; en las hembras, producen mayores efectos nocivos cuando se administran en la adultez. En la etapa perinatal y posnatal-preadultez, se encontraron efectos negativos de los DE sintéticos, tanto en machos como en hembras. La presente revisión da a conocer las oportunidades de estudios para continuar con investigaciones relacionadas a la exposición oral a DE.
This study investigated whether the coadministration of vitamin E (VitE) diminishes the harmful effects provoked by plasticizer bisphenol S (BPS) in the serum metabolites related to hepatic and renal ...metabolism, as well as the endocrine pancreatic function in diabetic male Wistar rats. Rats were divided into five groups (
= 5-6); the first group was healthy rats (Ctrl group). The other four groups were diabetic rats induced with 45 mg/kg bw of streptozotocin: Ctrl-D (diabetic control); VitE-D (100 mg/kg bw/d of VitE); BPS-D (100 mg/kg bw/d of BPS); The animals from the VitE + BPS-D group were administered 100 mg/kg bw/d of VitE + 100 mg/kg bw/d of BPS. All compounds were administered orally for 30 days. Body weight, biochemical assays, urinalysis, glucose tolerance test, pancreas histopathology, proximate chemical analysis in feces, and the activity of antioxidants in rat serum were assessed. The coadministration of VitE + BPS produced weight losses, increases in 14 serum analytes, and degeneration in the pancreas. Therefore, the VitE + BPS coadministration did not have a protective effect versus the harmful impact of BPS or the diabetic metabolic state; on the contrary, it partially aggravated the damage produced by the BPS. VitE is likely to have an additive effect on the toxicity of BPS.
Recent evidence suggests that hormonal effects on mitochondria could be mediated by mitochondrial estrogen receptors (mtERs). These receptors are new candidates for the beneficial estrogenic effects ...on mitochondria in different physiological conditions. The aim of this investigation was to study mtER expression during brain aging. We analyzed mtERα and mtERβ expression in cortical, hippocampal and hypothalamic mitochondria of young adult (3months) and aged (18months) female Wistar rats by Western blot. In addition, we explored the interaction of mtERβ with respiratory complex V by using coimmunoprecipitation assays. The results show that mtERα and mtERβ are present in young and aged brain mitochondria. We also demonstrate that mtERs are expressed as variants and have a brain region specific distribution. The predominant mtER variants detected were of 61 and 55KDa for mtERα and of 63 and 52KDa for mtERβ. However, we did not observe differences in the mtERα or β content between the two age groups studied. Additionally, we show that mtERβ interacts with complex V.
The overall results demonstrate that there is a differential expression of mtERα and mtERβ variants in different brain areas, indicating that they may participate in different functions in the brain during aging.