Adverse Effects Of Maternal Exposure Research Articles

Prenatal exposure to a mixture of different phthalates increases the risk of mammary carcinogenesis in F1 female offspring

Phthalates metabolites have been detected in the urine of pregnant and breastfeeding women. Thus, this study evaluated the adverse effects of maternal exposure to a mixture of six phthalates (Pth mix) on the mammary gland development and carcinogenesis in F1 female offspring. Pregnant female Sprague-Dawley rats were exposed daily to vehicle or Pth mix (35.22% diethyl-phthalate, 21.03% di-(2-ethylhexyl)-phthalate, 14.91% dibutyl-phthalate, 15.10% diisononyl-phthalate, 8.61% diisobutyl-phthalate, and 5.13% benzylbutyl-phthalate) by gavage at 20 μg/kg, 200 μg/kg or 200 mg/kg during gestational day 10 (GD 10) to postnatal day 21 (PND 21). After weaning (PND 22), some female offspring were euthanized for mammary gland analyses while other females received a single dose of N-methyl-N-nitrosourea (MNU, 50 mg/kg) or vehicle and then tumor incidence and multiplicity were recorded until PND 180. Maternal Pth mix exposure increased the number of Ki-67 and progesterone receptor-positive epithelial cells in the mammary gland from Pth mix 200 at μg/kg and 200 mg/kg groups. In addition, tumor incidence and mean number were higher only in Pth mix at 200 mg/kg when compared to the vehicle-treated group, and percentage of tumor-free animals was lower in Pth mix at 200 μg/kg and 200 mg/kg groups. The findings indicate that perinatal Pth mixture exposure increased susceptibility to MNU-induced mammary carcinogenesis in adult F1 female offspring.

Prenatal and postnatal mothering by diesel exhaust PM2.5-exposed dams differentially program mouse energy metabolism

BackgroundObesity is one of the leading threats to global public health. It is consequent to abnormal energy metabolism. Currently, it has been well established that maternal exposure to environmental stressors that cause inappropriate fetal development may have long-term adverse effects on offspring energy metabolism in an exposure timing-dependent manner, known as developmental programming of health and diseases paradigm. Rapidly increasing evidence has indicated that maternal exposure to ambient fine particles (PM2.5) correlates to abnormal fetal development. In the present study, we therefore assessed whether maternal exposure to diesel exhaust PM2.5 (DEP), the major component of ambient PM2.5 in urban areas, programs offspring energy metabolism, and further examined how the timing of exposure impacts this programming.ResultsThe growth trajectory of offspring shows that although prenatal maternal exposure to DEP did not impact the birth weight of offspring, it significantly decreased offspring body weight from postnatal week 2 until the end of observation. This weight loss effect of prenatal maternal exposure to DEP coincided with decreased food intake but not alteration in brown adipose tissue (BAT) morphology. The hypophagic effect of prenatal maternal exposure to DEP was in concord with decreased hypothalamic expression of an orexigenic peptide NPY, suggesting that the prenatal maternal exposure to DEP impacts offspring energy balance primarily through programming of food intake. Paradoxically, the reduced body weight resulted from prenatal maternal exposure to DEP was accompanied by increased mass of epididymal adipose tissue, which was due to hyperplasia as morphological analysis did not observe any hypertrophy. In direct contrast, the postnatal mothering by DEP-exposed dams increased offspring body weight during lactation and adulthood, paralleled by markedly increased fat accumulation and decreased UCP1 expression in BAT but not alteration in food intake. The weight gain induced by postnatal mothering by DEP-exposed dams was also expressed as an increased adiposity. But it concurred with a marked hypertrophy of adipocytes.ConclusionPrenatal and postnatal mothering by DEP-exposed dams differentially program offspring energy metabolism, underscoring consideration of the exposure timing when examining the adverse effects of maternal exposure to ambient PM2.5.

Adverse effects of maternal exposure to bisphenol F on the anxiety- and depression-like behavior of offspring.

Bisphenol A (BPA), a well-known endocrine disruptor, is metabolized and eliminated rapidly from the body in adult animals. However, many authors have reported that perinatal BPA exposure alters development of the brain, reproductive system and behavior in the next generation. Recently, BPA substitutes, especially bisphenol F (BPF), have been used because of concerns about the influence of BPA on children, although the actual effects on the next generation are unknown. In this study, we observed behavioral adverse effects of the offspring of mice exposed to BPA or BPF in fetal period. Female C57BL/6 mice were given oral BPA or BPF (0 or 10 mg/kg body weight) daily from gestational day 11.5 to 18.5. The open field test, the elevated plus maze test and the forced swim test were performed at postnatal week 10. BPF exposure altered offspring behavior significantly, resulting in increases in anxiety and depressive state. The influence of BPF was stronger than that of BPA. We demonstrated novel evidence that BPF influences the behavior of offspring.

Prenatal exposure to PM10 and NO2 and children's neurodevelopment from birth to 24 months of age: Mothers and Children's Environmental Health (MOCEH) study

IntroductionPrevious studies have suggested adverse effects of maternal exposure to air pollution on neurodevelopment in early childhood. ObjectivesWe aimed to investigate the association between prenatal exposure to particulates of less than 10μm in diameter (PM10) and nitrogen dioxide (NO2) and neurodevelopment in children during the first 24months of their lives. MethodsThe MOCEH study is a prospective birth cohort study in South Korea. Average exposure levels to PM10 and NO2 during the entire pregnancy were estimated using the inverse distance weighting (IDW) method. A total of 520 mother–child pairs who completed neurodevelopmental assessments using the Korean Bayley Scale of Infant Development II (K-BSID-II) more than once at ages of 6, 12 and 24months were included. Mental developmental index (MDI) and psychomotor developmental index (PDI) from the K-BSID-II were used as outcome variables. ResultsThere were negative associations between maternal exposure to PM10 and MDI (β=−2.83; p=0.003) and PDI (β=−3.00; p=0.002) throughout the first 24months of life as determined by the generalized estimating equation (GEE) model. Maternal NO2 exposure was related with impairment of psychomotor development (β=−1.30; p=0.05) but not with cognitive function (β=−0.84; p=0.20). In a multiple linear regression model, there were significant effects of prenatal air pollution exposure on MDI (PM10: β=−4.60; p<0.001, NO2: β=−3.12; p<0.001) and PDI (PM10: β=−7.24; p<0.001, NO2: β=−3.01; p<0.001) at 6months, but no significant association was found at 12 and 24months of age. ConclusionsThe findings suggest that exposure to air pollution may result in delayed neurodevelopment in early childhood.

Potential Teratogenicity of Methimazole: Exposure of Zebrafish Embryos to Methimazole Causes Similar Developmental Anomalies to Human Methimazole Embryopathy

While methimazole (MMI) is widely used in the therapy for hyperthyroidism, several groups have reported that maternal exposure to MMI results in a variety of congenital anomalies, including choanal and esophageal atresia, iridic and retinal coloboma, and delayed neurodevelopment. Thus, adverse effects of maternal exposure to MMI on fetal development have long been suggested; however, direct evidence for the teratogenicity of MMI has not been presented. Therefore, we studied the effects of MMI on early development by using zebrafish as a model organism. The fertilized eggs of zebrafish were collected immediately after spawning and grown in egg culture water containing MMI at various concentrations. External observation of the embryos revealed that exposure to high concentrations of MMI resulted in loss of pigmentation, hypoplastic hindbrain, turbid tissue in the forebrain, swelling of the notochord, and curly trunk. Furthermore, these effects occurred in a dose-dependent manner. Precise observation of the serial cross-sections of MMI-exposed embryos elucidated delayed development and hypoplasia of the whole brain and spinal cord, narrowing of the pharynx and esophagus, severe disruption of the retina, and aberrant structure of the notochord. These neuronal, pharyngeal, esophageal, and retinal anomalous morphologies have a direct analogy to the congenital anomalies observed in children exposed to MMI in utero. Here, we show the teratogenic effects of MMI on the development of zebrafish and provide the first experimental evidence for the connection between exposure to MMI and human MMI embryopathy.

Dichloroacetonitrile induces oxidative stress and developmental apoptotic imbalance in mouse fetal brain

Dichloroacetonitrile (DCAN) is one of the disinfection by-products of chlorination of drinking water. Limited mechanistic studies exist on the developmental toxicity of haloacetonitriles (HANs). The present study was designed to investigate the potential adverse effects of maternal exposure to DCAN on mouse fetal brain. Based on initial dose–response experiment, DCAN (14 mg/kg/day) was administered orally to pregnant mice at gestation day (GD) 6, till GD 15. Maternal exposure to DCAN resulted in redox imbalance in fetal cortex and cerebellum, characterized by significant decrease in reduced glutathione (GSH), and elevation of malondialdehyde (MDA) level and superoxide dismutase (SOD) activity. Further, DCAN induced apoptosis indicated by significant enhancement of DNA fragmentation and active caspase-3 level in fetal cortex and cerebellum. Neuronal degeneration was indicated by positive cupric silver staining. In conclusion, maternal exposure to DCAN adversely affects mouse fetal brain as evidenced by induction of oxidative stress, apoptotic imbalance and neurodegeneration.

Traffic-related air pollution and pregnancy outcomes in the Dutch ABCD birth cohort study

ObjectivesThere is growing evidence for an adverse effect of maternal exposure to air pollution on pregnancy outcomes. As European data on this topic are limited, the aim of this study...

Chloroacetonitrile induces oxidative stress and apoptosis in mouse fetal liver

Chloroacetonitrile (CAN) is a disinfection by-product of chlorination of drinking water. The present study was designed to investigate the potential adverse effects of maternal exposure to CAN on fetal liver in mice. Based on an initial dose–response experiment, CAN (25 mg/(kg day)) was given orally to pregnant mice at gestation day (GD) 6, till GD 18. Fetuses were collected and fetal livers were used for assessing oxidative status, apoptosis and histopathological changes. Maternal exposure to CAN resulted in observed oxidative stress and redox imbalance in fetal liver tissues as marked by significant decrease in reduced glutathione (GSH) and elevation of oxidized glutathione (GSSG), malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in genomic DNA. Further, CAN induced apoptosis as indicated by a significant increase in binding of Hoechst reagent to damaged DNA fragments of fetal liver and enhancement of the activity of caspase-3 in cytosolic fractions of fetal livers. Histopathological examination of fetal livers of CAN-treated mice showed hepatocytes with vacuolated cytoplasm, karyolysis and karyorrhexis as well as depletion of their glycogen content. In conclusion, maternal exposure to CAN adversely affects mouse fetal livers as evidenced by the induction of oxidative stress, apoptosis and histopathological changes.

Effects of the GSTM1 and GSTT1 polymorphisms on the relationship between maternal exposure to environmental tobacco smoke and neonatal birth weight.

The purpose of the investigation was to determine whether genetic polymorphisms in enzymes that metabolize exogenous chemicals modulate the effects of environmental tobacco smoke (ETS) exposure on birth weight. A survey was conducted from 2000 to 2001 among 266 pregnant women who were hospitalized for delivery and on their singleton live births. We determined maternal GSTM1 and GSTT1 polymorphisms by polymerase chain reaction and measured the urinary cotinine of pregnant women at delivery by radioimmunoassay. Birth weight was found to decrease significantly with increasing concentrations of maternal urinary cotinine (P < 0.05). The interactive effect of exposure to ETS and the presence of the GSTT1 polymorphism was found to be significant by multivariate analysis (P < 0.01), whereas the interactive effect of exposure to ETS and the presence of GSTM1 polymorphism did not reach statistical significance (P = 0.21). A combination of the GSTM1-null and the GSTT1 null-genotypes was found to exacerbate the effect of maternal exposure to ETS on birth weight more than the presence of either genotype alone. Our data indicate that maternal exposure to ETS negatively affects neonatal birth weight, and the adverse effect of maternal exposure to ETS on neonatal birth weight could be modified by the maternal metabolic genotypes, GSTM1 and GSTT1.