Search

The potent immunomodulatory effect of the endocrine disruptor bisphenol A during development and consequences during life span are of increasing concern. Particular interests have been raised from animal studies regarding the risk of developing food intolerance and infection. We aimed to identify immune disorders in mice triggered by perinatal exposure to bisphenol A. Gravid mice were orally exposed to bisphenol (50 μg/kg body weight/day) from day 15 of pregnancy until weaning. Gut barrier function, local and systemic immunity were assessed in adult female offspring. Mice perinatally exposed to bisphenol showed a decrease in ileal lysozyme expression and a fall of fecal antimicrobial activity. In offspring mice exposed to bisphenol, an increase in colonic permeability was observed associated with an increase in interferon-γ level and a drop of colonic IgA cells and fecal IgA production. Interestingly, altered frequency of innate lymphoid cells type 3 occurred in the small intestine, with an increase in IgG response against commensal bacteria in sera. These effects were related to a defect in dendritic cell maturation in the lamina propria and spleen. Activated and regulatory T cells were decreased in the lamina propria. Furthermore, perinatal exposure to bisphenol promoted a sharp increase in interferon-γ and interleukin-17 production in the intestine and elicited a T helper 17 profile in the spleen. To conclude, perinatal exposure to bisphenol weakens protective and regulatory immune functions in the intestine and at systemic level in adult offspring. The increased susceptibility to inflammatory response is an interesting lead supporting bisphenol-mediated adverse consequences on food reactions and infections. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the role of apoptosis in the development of the newborn cochlear structures and hearing loss caused by prenatal cis-diaminedichloroplatinum (cisplatin) exposure. Pregnant albino guinea pigs were intraperitoneally injected with 1.5 mg/kg body weight cisplatin once a day for seven consecutive days at gestational day (GD) 51 to GD 57. At postnatal day (PND) 14, pups were examined in the distortion product otoacoustic emission (DPOAE) task. The temporal bones were then removed and immunohistochemically stained for caspase 3, using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method. Cisplatin used during pregnancy could induce hearing loss in newborn and cochlear hair cell apoptosis. In conclusion, apoptosis may play an important role in the development of hearing impairment, caused by perinatal cisplatin exposure. [ABSTRACT FROM AUTHOR]

Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are environmental pollutants that cause neurobehavioral deficits in humans. Because exposures to MeHg and PCBs occur through fish consumption, it is necessary to clarify the effects of the interaction of the two pollutants. Therefore, we investigated the effects of perinatal exposure to MeHg and PCBs on the neurobehavioral development in mice. Female mice (C57BL/6Cr) were divided into four groups according to the type of exposure: (1) vehicle control, (2) MeHg alone, (3) PCBs alone, and (4) MeHg + PCBs. The MeHg-exposed groups were fed with a diet containing 5 ppm MeHg (as Hg), from 4 weeks before mating, throughout pregnancy, and lactation. The PCB-exposed groups were given a commercial mixture of PCBs, Aroclor 1254, at 18 mg/kg body weight in corn oil by gavage every 3 days from day 5 after breeding and continued until postnatal day (PND) 20. Before weaning, an assessment of eye opening showed the interactive effects between MeHg and PCBs on PND 12: The coexposure group showed a similar response to the control group, whereas the MeHg- and PCB-exposed groups showed a high response than the former two groups. We also observed delay in development of grasp reflex by MeHg exposure on PNDs 12 and 14. When the offspring mice were 8 weeks old, the group exposed to PCBs alone showed increases in the frequencies of excrement defecation and urine traces in an open-field test. Analysis of the latency revealed the antagonistic interaction between the MeHg and PCBs: The latency increased by either MeHg or PCB exposure was decreased by coexposure. Treatment with MeHg decreased the distance walked by the mice, and MeHg interacted with PCBs. Moris’ water maze test showed that the MeHg-treated mice took a long time to reach the submerged platform; however, this MeHg exposure showed no interaction with PCB exposure. The spontaneous locomotion activity of the mice was not affected by the chemical exposure at 9 weeks of age. These behavioral changes were not accompanied by any histopathological changes at the levels of the frontal cortex-caudoputamen, hippocampus-amygdala, brainstem and cerebellum. These results show that perinatal coexposure to MeHg and PCBs produces no additive or synergistic effects. This phenomenon needs to be further investigated. [ABSTRACT FROM AUTHOR]

Because behavioral deficits associated with gestational exposure to polychlorinated biphenyls (PCBs) have been a concern, we studied the developmental and neurobehavioral effects of perinatal exposure to Aroclor 1254 (A1254), a commercial mixture of PCBs, in mice. The PCB mixture (A1254; 0, 6, 18, and 54 mg/kg body weight) was administered to pregnant mice (C57BL/6Cr) every 3 days by gavage from gestational day (GD) 6 to postnatal day (PND) 20. Compared with the control, treatment with A1254 did not alter the maternal body weight during the gestation and lactation periods. The body weight of the offspring did not differ among treatments. To assess the effects on offspring following such exposure, physical and neurobehavioral development (i.e., pinna detachment, hair growth, eye opening, incisor eruption, grasp reflex, righting reflex, walking, negative geotaxis, and cliff avoidance) was observed before weaning. At PND 7, poor adult-like responses in negative geotaxis were observed in all exposed groups. When the offspring were at 8-week old, the PCB-treated (18 mg/kg body weight) mice showed a decreased walking speed in the open-field test, and a prolonged time to reach the platform in the water maze test. Spontaneous locomotion activity was not affected by PCB exposure at 9 weeks . These results showed that perinatal exposure to PCBs produces several behavioral alterations in mice. Although dose-dependent changes were not observed, the neurobehavioral effects such as a decreased walking speed in the open-field test and a prolonged time to reach the platform in the water maze test remained in adulthood after the seeming recovery from the transient delay in development before weaning. [ABSTRACT FROM AUTHOR]

We previously performed dose–response studies of genistein, diisononyl phthalate, 4-nonylphenol, methoxychlor (MXC), and bisphenol A to examine the impact of maternal dietary exposure from gestational day 15 to postnatal day 10 on the development of rat reproductive system in later life. Among the chemicals MXC alone showed typical estrogenic effects only at the maternally toxic 1200 ppm. The present study was performed to examine the sensitivity of immunohistochemical analysis of pituitary cells of offspring similarly exposed to each chemical for detection of endocrine-disrupting effects. For this purpose, ratios of pituitary cells expressing luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL), were measured at 3 and 11 weeks of age. Ethinylestradiol (EE) at 0.5 ppm was used as a reference chemical. At week 3, decrease in the relative proportions of LH, FSH, and PRL cells in males and LH cells in females was evident with MXC at 1200 ppm. At week 11, increase was found for PRL cells from 240 ppm MXC, and FSH cells at 1200 ppm in females. On the other hand, EE increased the PRL cell percentage in females at week 3 but no effects were apparent at week 11. The other chemicals were without influence at either time point. The results suggest that the assessment of the pituitary cell populations might be a more sensitive approach to detect perinatal endocrine-disrupting effects than other methods. The difference in the pituitary effect between MXC and EE is discussed. [ABSTRACT FROM AUTHOR]