Prenatal Exposures of Male Rats to the Environmental Chemicals Bisphenol A and Di(2-Ethylhexyl) Phthalate Impact the Sexual Differentiation Process

Background: The general population (including children) is exposed to chemical mixtures. Plasticizers such as Bisphenol A (BPA) and Phthalates (mainly Bis(2-ethylhexyl) phthalate-DEHP) are widespread contaminants classified as endocrine disrupters which share some toxicological profiles and coexist in food and environment. Methods: To identify hazards of DEHP and BPA mixtures, the juvenile toxicity test—where rodents are in peripubertal phase of development, resembling childhood—was selected using exposure data from biomonitoring study in children. Biological activity and potential enhanced and/or reduced toxicological effects of mixtures due to common mechanisms were studied, considering endpoints of metabolic, endocrine and reproductive systems. The degree of synergy or antagonism was evaluated by synergy score calculation, using present data and results from the single compound individually administered. Results: In metabolic system, synergic interaction predominates in female and additive in male rats; in the reproductive and endocrine systems, the co-exposure of BPA and DEHP showed interactions mainly of antagonism type. Conclusions: The present approach allows to evaluate, for all the endpoints considered, the type of interaction between contaminants relevant for human health. Although the mode of action and biological activities of the mixtures are not completely addressed, it can be of paramount usefulness to support a more reliable risk assessment.

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Effect of prenatal exposure to bisphenol A on the serum testosterone concentration of rats at birth

Human & Experimental Toxicology ◽

10.1191/0960327106ht638oa ◽

2006 ◽

Vol 25 (7) ◽

pp. 369-373 ◽

Cited By ~ 31

Author(s):

M Tanaka ◽

S Nakaya ◽

M Katayama ◽

H Leffers ◽

S Nozawa ◽

...

Keyword(s):

Bisphenol A ◽

Sexual Differentiation ◽

Neonatal Period ◽

Serum Testosterone ◽

In Utero ◽

Female Rats ◽

Male Rats ◽

Testosterone Concentration ◽

Fetal Serum ◽

And Control

In the rat, testosterone (T) in the neonatal period plays an important role in sexual differentiation and there is a serum T surge in male rats 2 hours after birth. Pregnant female rats were exposed to various doses of bisphenol A (BPA) from gestational day 1 (GD1) through 2 hours after parturition. About half of the BPA-exposed and control dams were subjected to cesarean section on GD22. The male fetuses on GD22 were immediately sacrificed and blood was collected. The other half of the BPA-treated and control dams delivered at GD23 (parturition day). The male pups were sacrificed 2 hours after birth. Serum T concentration was determined by radioimmunoassay (RIA). The BPA concentration in the fetal serum on GD22 increased inversely to the T levels in the serum. The T concentration in the pups' serum 2 hours after birth decreased inversely to the BPA concentration in the serum. However, there were no differences in the serum T concentration among the various doses of BPA. These results suggest that exposure to BPA in utero inhibits the T surge in the neonatal period and we speculate that exposure to BPA in utero disrupts the endocrine environment in the neonatal male.

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Environmental exposures to endocrine disrupting chemicals (EDCs) and their role in endometriosis: a systematic literature review

Reviews on Environmental Health ◽

10.1515/reveh-2020-0046 ◽

2020 ◽

Vol 0 (0) ◽

Cited By ~ 1

Author(s):

Diksha Sirohi ◽

Ruqaiya Al Ramadhani ◽

Luke D. Knibbs

Keyword(s):

Bisphenol A ◽

Phthalate Esters ◽

Endocrine Disrupting Chemicals ◽

Environmental Pollutants ◽

Positive Association ◽

Environmental Chemicals ◽

Reproductive Age ◽

Organochlorinated Pesticides ◽

Endocrine Disrupting ◽

The Relationship

AbstractPurposeEndocrine-related diseases and disorders are on the rise globally. Synthetically produced environmental chemicals (endocrine-disrupting chemicals (EDCs)) mimic hormones like oestrogen and alter signalling pathways. Endometriosis is an oestrogen-dependent condition, affecting 10–15% of women of the reproductive age, and has substantial impacts on the quality of life. The aetiology of endometriosis is believed to be multifactorial, ranging from genetic causes to immunologic dysfunction due to environmental exposure to EDCs. Hence, we undertook a systematic review and investigated the epidemiological evidence for an association between EDCs and the development of endometriosis. We also aimed to assess studies on the relationship between body concentration of EDCs and the severity of endometriosis.MethodFollowing PRISMA guidelines, a structured search of PubMed, Embase and Scopus was conducted (to July 2018). The included studies analysed the association between one or more EDCs and the prevalence of endometriosis. The types of EDCs, association and outcome, participant characteristics and confounding variables were extracted and analysed. Quality assessment was performed using standard criteria.ResultsIn total, 29 studies were included. Phthalate esters were positively associated with the prevalence of endometriosis. The majority (71%) of studies revealed a significant association between bisphenol A, organochlorinated environmental pollutants (dioxins, dioxin-like compounds, organochlorinated pesticides, polychlorinated biphenyls) and the prevalence of endometriosis. A positive association between copper, chromium and prevalence of endometriosis was demonstrated in one study only. Cadmium, lead and mercury were not associated with the prevalence of endometriosis. There were conflicting results for the association between nickel and endometriosis. The relationship of EDCs and severity of endometriosis was not established in the studies.ConclusionWe found some evidence to suggest an association between phthalate esters, bisphenol A, organochlorinated environmental pollutants and the prevalence of endometriosis. Disentangling these exposures from various other factors that affect endometriosis is complex, but an important topic for further research.

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Neuroendocrine disruption by bisphenol A and/or di(2-ethylhexyl) phthalate after prenatal, early postnatal and lactational exposure

Environmental Science and Pollution Research ◽

10.1007/s11356-021-12408-9 ◽

2021 ◽

Author(s):

Anil Yirun ◽

Gizem Ozkemahli ◽

Aylin Balci ◽

Pinar Erkekoglu ◽

Naciye Dilara Zeybek ◽

...

Keyword(s):

Bisphenol A ◽

Lactational Exposure ◽

Ethylhexyl Phthalate

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Study of Endocrine Disruptors in the Sediment of a South Brazilian River

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.1120-1121.862 ◽

2015 ◽

Vol 1120-1121 ◽

pp. 862-866

Author(s):

Irajá Do Nascimento ◽

Nathália Christine Vieceli ◽

Michele Schmitz ◽

Fernanda Glaeser

Keyword(s):

Gas Chromatography ◽

Bisphenol A ◽

Endocrine Disruptors ◽

River Sediment ◽

Flame Ionization Detection ◽

River Contamination ◽

Ionization Detection ◽

Flame Ionization ◽

Organic Extracts ◽

Ethylhexyl Phthalate

This study investigated the occurrence of di (2-ethylhexyl) phthalate (DEHP) di-n-butylphthalate (DBP) and bisphenol A (BPA) in river sediment. The samples were collected from three selected points and extracted by sonication, using n-hexane and ethanol. The organic extracts were analyzed by gas chromatography with flame ionization detection (GC/FID). DBP and BPA were not detected. The average concentrations of DEHP range from 0.72 (±0.04) to 27.90 (± 3.05) ng g-1 of sediment. The best solvent for the extractions was n-hexane. However ethanol also shows good extraction yields of DEHP. These results showed an important anthropic contribution for the river contamination by endocrine disruptors.

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Uptake of Phthalate Esters, Di(n-butyl)phthalate and Di(2-ethylhexyl)phthalate, as Environmental Chemicals in Monkeys in Japan

Bulletin of Environmental Contamination and Toxicology ◽

10.1007/s001280000057 ◽

2000 ◽

Vol 64 (5) ◽

pp. 679-685 ◽

Cited By ~ 5

Author(s):

K. Asaoka

Keyword(s):

Phthalate Esters ◽

Environmental Chemicals ◽

Butyl Phthalate ◽

Ethylhexyl Phthalate

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Behavioral Alterations in Response to Fear-Provoking Stimuli and Tranylcypromine Induced by Perinatal Exposure to Bisphenol A and Nonylphenol in Male Rats

Environmental Health Perspectives ◽

10.1289/ehp.6961 ◽

2004 ◽

Vol 112 (11) ◽

pp. 1159-1164 ◽

Cited By ~ 99

Author(s):

Takayuki Negishi ◽

Katsuyoshi Kawasaki ◽

Shingo Suzaki ◽

Haruna Maeda ◽

Yoshiyuki Ishii ◽

...

Keyword(s):

Bisphenol A ◽

Male Rats ◽

Perinatal Exposure ◽

Behavioral Alterations

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Altered sexual differentiation of hepatic uridine diphosphate glucuronyltransferase by neonatal hormone treatment in rats

Biochemical Journal ◽

10.1042/bj1800313 ◽

1979 ◽

Vol 180 (2) ◽

pp. 313-318 ◽

Cited By ~ 30

Author(s):

Coral A. Lamartiniere ◽

Cindy S. Dieringer ◽

Etsuko Kita ◽

George W. Lucier

Keyword(s):

Enzyme Activity ◽

Adult Male ◽

Sexual Differentiation ◽

Reproductive Tract ◽

Testosterone Propionate ◽

Hormone Treatment ◽

Male Rats ◽

Ventral Prostate ◽

Uridine Diphosphate ◽

Neonatal Administration

The hepatic microsomal enzyme UDP-glucuronyltransferase undergoes a complex developmental pattern in which enzyme activity is first detectable on the 18th day of gestation in rats. Prepubertal activities are similar for males and females. However, postpubertal sexual differentiation of enzyme activity occurs in which male activities are twice those of females. Neonatal administration of testosterone propionate or diethylstilboestrol to intact animals resulted in lowered UDP-glucuronyltransferase activity in liver microsomal fractions of adult male rats, whereas no changes were observed in the adult females and prepubertal male and female animals. Neonatal administration of testosterone propionate and diethylstilboestrol adversely affected male reproductive-tract development as evidenced by decreased weights of testes, seminal vesicles and ventral prostate. Diethylstilboestrol also markedly decreased spermatogenesis. Hypophysectomy of adult male rats resulted in negative modulation of microsomal UDP-glucuronyltransferase and prevented the sexual differentiation of enzyme activity. In contrast hypophysectomy had no effect on female UDP-glucuronyltransferase activity. A pituitary transplant under the kidney capsule was not capable of reversing the enzyme effects of hypophysectomy, therefore suggesting that the male pituitary factor(s) responsible for positive modulation of UDP-glucuronyltransferase might be under hypothalamic control in the form of a releasing factor. Neonatal testosterone propionate and diethylstilboestrol administration apparently interfered with the normal sequence of postpubertal UDP-glucuronyltransferase sexual differentiation.

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