Maternal exposure to a mixture of Bisphenol A and Diethyl Hexyl Phthalate predisposes female offspring to growth retardation and metabolic dysfunction in adulthood

Bisphenol A (BPA) is a chemical compound that has adverse health outcomes in adults when exposed during the perinatal period. However, its effect on cardiovascular function remains to be elucidated. In this study, we examined the effects of daily administration of BPA to pregnant mice from gestational days 11 to 19 on cardiometabolic outcomes in the adult offspring. Prenatal BPA exposure resulted in altered growth trajectory and organ size, increase adiposity and impaired glucose homeostasis in male and female offspring. In addition, these BPA offspring exhibited raised systolic blood pressure, and in the males this was accompanied by impaired vascular tone. The aortas in females, but not in males, from the BPA group also showed reduced estrogen receptor gene expression. These results indicate that prenatal exposure to BPA increased susceptibility of the offspring to developing cardiovascular and metabolic dysfunction later in life.

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Bisphenol A Exposure during Pregnancy Alters the Mortality and Levels of Reproductive Hormones and Genes in Offspring Mice

BioMed Research International ◽

10.1155/2017/3585809 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 12

Author(s):

Shuang Ma ◽

Wanyu Shi ◽

Xiaodan Wang ◽

Pengyan Song ◽

Xiuhui Zhong

Keyword(s):

Bisphenol A ◽

Reproductive Toxicity ◽

Female Offspring ◽

Reproductive Hormones ◽

Maternal Exposure ◽

Adult Offspring ◽

Mrna Levels ◽

Protein Levels ◽

Pregnant Mice ◽

Exposure During Pregnancy

The present study investigated the reproductive toxicity of bisphenol A (BPA) exposure to the mother on the offspring mice. BPA was given to pregnant mice at 50 mg/kg, 500 mg/kg, and 2500 mg/kg BW BPA daily by gavage during the whole gestation period. The offspring mice were sacrificed at 8 weeks of age. Results showed that exposure of BPA to the mother increased the mortality (P<0.05). Maternal exposure of BPA reduced the levels of T (♂) and FSH (♀) (P<0.01) and elevated E2 (♀) level in the adult offspring (P<0.01). BPA exposure caused testicular damage as shown by less Leydig cells and ovarian injury as shown by more vacuoles and less corpus granules in the adult offspring mice. Immunohistochemistry revealed that maternal exposure of BPA increased Bax and decreased Bcl-2 at the protein levels in testicular and ovary tissues in the offspring mice. BPA significantly reduced the expression of StAR in male offspring (P<0.05). Interestingly, the mRNA levels of Cyp11a were significantly decreased in 50 mg/kg groups and were increased in 500 mg/kg group in the males. Reduced Kitlg and elevated Amh at the mRNA levels were detected in the female offspring.

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Faculty Opinions recommendation of Pre-natal exposure of mice to bisphenol A elicits an endometriosis-like phenotype in female offspring.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.2788957.4297071 ◽

2010 ◽

Author(s):

Dariusz J Skarzynski ◽

Marta Siemieniuch

Keyword(s):

Bisphenol A ◽

Female Offspring

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MATERNAL EXPOSURE TO DDE MAY INCREASE WEIGHT AND BODY-MASS IN ADULT FEMALE OFFSPRING

Epidemiology ◽

10.1097/00001648-200407000-00299 ◽

2004 ◽

Vol 15 (4) ◽

pp. S117-S118 ◽

Cited By ~ 2

Author(s):

Wilfried Karmaus ◽

Ihuoma Eneli

Keyword(s):

Body Mass ◽

Adult Female ◽

Female Offspring ◽

Maternal Exposure

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A birth cohort study to investigate the association between prenatal phthalate and bisphenol A exposures and fetal markers of metabolic dysfunction

Environmental Health ◽

10.1186/1476-069x-13-84 ◽

2014 ◽

Vol 13 (1) ◽

Cited By ~ 44

Author(s):

Jillian Ashley-Martin ◽

Linda Dodds ◽

Tye E Arbuckle ◽

Adrienne S Ettinger ◽

Gabriel D Shapiro ◽

...

Keyword(s):

Cohort Study ◽

Bisphenol A ◽

Birth Cohort ◽

Birth Cohort Study ◽

Metabolic Dysfunction

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Pre-natal exposure of mice to bisphenol A elicits an endometriosis-like phenotype in female offspring

General and Comparative Endocrinology ◽

10.1016/j.ygcen.2010.03.030 ◽

2010 ◽

Vol 168 (3) ◽

pp. 318-325 ◽

Cited By ~ 67

Author(s):

Pietro G. Signorile ◽

Enrico P. Spugnini ◽

Luigi Mita ◽

Pasquale Mellone ◽

Alfredo D’Avino ◽

...

Keyword(s):

Bisphenol A ◽

Female Offspring

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Female offspring born to obese and insulin-resistant dams are not at increased risk for obesity and metabolic dysfunction during early development

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2017-0371 ◽

2018 ◽

Vol 96 (1) ◽

pp. 97-102 ◽

Cited By ~ 1

Author(s):

Hanin Aburasayn ◽

Rami Al Batran ◽

Keshav Gopal ◽

Malak Almutairi ◽

Amina Eshreif ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Female Offspring ◽

Metabolic Dysfunction ◽

Insulin Resistant ◽

The Metabolic Syndrome ◽

Rate Versus ◽

Increased Risk ◽

Study Completion ◽

Reduced Rate

The percentage of women who are obese at the time of conception or during pregnancy is increasing, with animal and human studies demonstrating that offspring born to obese dams or mothers are at increased risk for obesity and the metabolic syndrome. Our goal was to confirm in an experimental model of metabolic syndrome in the dam, whether the offspring would be at increased risk of obesity. Conversely, we observed that male offspring born to dams with metabolic syndrome had no alterations in their body mass profiles, whereas female offspring born to dams with metabolic syndrome were heavier at weaning, but exhibited no perturbations in energy metabolism. Moreover, they gained weight at a reduced rate versus female offspring born to healthy dams, and thus weighed less at study completion. Hence, our findings suggest that factors other than increased adiposity and insulin resistance during pregnancy are responsible for the increased risk of obesity in children born to obese mothers.

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Perinatal oral exposure to low doses of bisphenol A, S or F impairs gut barrier and immune functions in female offspring mice

10.21203/rs.2.17347/v1 ◽

2019 ◽

Author(s):

Yann Malaisé ◽

Corinne Lencina ◽

Christel Cartier ◽

Maïwenn Olier ◽

Sandrine Ménard ◽

...

Keyword(s):

Adverse Effects ◽

Immune Responses ◽

Bisphenol A ◽

Low Dose ◽

Intestinal Barrier ◽

Female Offspring ◽

Oral Exposure ◽

Gut Barrier ◽

Cellular Immune Responses ◽

Cellular Immune

Abstract Background Bisphenol A (BPA), one of the highest-volume chemicals produced worldwide, has been identified as an endocrine disruptor. Many peer-reviewing studies have reported adverse effects of low dose BPA exposure, particularly during perinatal period (gestation and/or lactation). We previously demonstrated that perinatal oral exposure to BPA (via gavage of mothers during gestation and lactation) has long-term consequences on immune response and intestinal barrier functions. Due to its adverse effects on several developmental and physiological processes, BPA was removed from consumer products and replaced by chemical substitutes such as BPS or BPF, that are structurally similar and not well studied compare to BPA. Here, we aimed to compare perinatal oral exposure to these bisphenols (BPs) at two doses (5 and 50 mg/kg body weight (BW)/day (d)) on gut barrier and immune system in female offspring mice at adulthood (Post Natal Day PND70). Methods Pregnant female mice were orally exposed to BPA, BPS or BPF at 5 or 50 μg/kg BW/d from 15th day of gravidity to weaning of pups at PostNatal Day (PND) 21. Gut barrier function and the humoral and cellular immune responses of adult offspring (PND70) were analysed at intestinal and systemic levels. Results In female offspring, perinatal oral BP exposure led to adverse effects on intestinal barrier and immune response that were dependant of the BP nature (A, S or F) and dose of exposure. Stronger impacts were observed with BPS at the dose of 5µg/kg BW/d on inflammatory markers in feces associated with an increase of anti-E. coli IgG, revealing a defect of gut barrier. BPA and BPF exposure induced prominent changes at low dose in offspring mice, in term of gut barrier functions and cellular immune responses, provoking an intestinal and systemic Th1/Th17 inflammation. Conclusion These findings provide, for the first time, a comparative study of long-time consequences of BPA, S and F perinatal exposure by oral route in offspring mice. This work warms that it is mandatory to consider immune markers and dose in risk assessment associated to new BPA’s alternatives. Keywords: Bisphenol A, Bisphenol S, Bisphenol F, Immune responses, Perinatal exposure, Intestine, Th1/Th17, immunoglobulin, cytokines

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