Influence of in utero di-n-hexyl phthalate and dicyclohexyl phthalate on fetal testicular development in rats

Ahbab, Müfide Aydoğan; Barlas, Nurhayat

doi:10.1016/j.toxlet.2015.01.015

Cited by 25 publications

(9 citation statements)

References 51 publications

(68 reference statements)

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“…Animal as well as epidemiological studies in infants and children have found various health effects of specific phthalates, including abnormal reproductive outcomes ( Meeker et al 2009 ; Abdel-Maksoud et al 2015 ; Niermann et al 2015 ; Aydoğan Ahbab and Barlas 2015 ; Jurewicz and Hanke 2011 ), children’s neurodevelopmental and behavioral problems ( Whyatt et al 2012 ; Ejaredar et al 2015 ; Braun et al 2013 ), and asthma and allergies ( Bornehag et al 2004b ; Whyatt et al 2014 ; Stelmach et al 2015 ; Just et al 2012 ; Hsu et al 2012 ), although not consistently.…”

Section: Introductionmentioning

confidence: 99%

Prenatal Exposure to Phthalates and the Development of Eczema Phenotypes in Male Children: Results from the EDEN Mother–Child Cohort Study

Soomro

Baïz

Philippat

et al. 2018

Environ Health Perspect

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Background:Contradictory results exist regarding the importance of early-life exposure to phthalates for development of childhood eczema.Objectives:We evaluated the association between maternal urinary concentrations of phthalate metabolites between the 24th and 28th week of gestation and occurrence of eczema in their sons up to 5 y of age, according to allergic sensitization as assessed by total immunoglobulin E (IgE) in a subsample of individuals.Methods:Data on health outcomes and background factors were collected using five standardized annual questionnaires completed by parents at the children’s ages of 1–5 y, and their associations with phthalate metabolite urinary concentrations were assessed in 604 mother–son pairs with adjusted multiple logistic regression and Cox’s survival model. Several eczema phenotypes were considered. Atopic status was assessed at 5 y of age in 293 boys through total IgE assessment.Results:At 5 y of age, the prevalence of ever eczema was 30.4%. Metabolites of di-isobutyl phthalate (DiBP) and di-isononyl phthalate (DiNP) were positively associated with early-onset (0–24 mo of age) eczema (15.7%) and late-onset (24–60 mo of age) eczema (14.7%). Applying the Cox’s model showed a significant association of occurrence of eczema in the first 5 y of life with DiBP and DiNP metabolites. Among IgE-sensitized boys, metabolites of di-n-butyl phthalate (DBP) and DiBP were significantly associated with ever eczema {hazard ratio (HR)=1.67 [95% confidence interval (CI): 1.10, 2.54], p=0.01 and HR=1.87 (95% CI: 1.01, 3.48), p=0.04, respectively}.Conclusions:Occurrence of eczema in early childhood may be influenced by prenatal exposure to certain phthalates in boys. Further investigations are needed to confirm this observation. https://doi.org/10.1289/EHP1829

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Section: Introductionmentioning

confidence: 99%

Prenatal Exposure to Phthalates and the Development of Eczema Phenotypes in Male Children: Results from the EDEN Mother–Child Cohort Study

Soomro

Baïz

Philippat

et al. 2018

Environ Health Perspect

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“… DHP : di- n -hexyl phthalate; DCHP: dicyclohexyl phthalate. a Numbers represent mean ± SE. Statistically different from the control group ( p < 0.05). b The marked data were published previously (Aydoğan Ahbab and Barlas, 2015). …”

Section: Resultsmentioning

confidence: 99%

Comparative developmental toxicity evaluation of di-n-hexyl phthalate and dicyclohexyl phthalate in rats

et al. 2017

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To investigate the effects of di- n-hexyl phthalate (DHP) and dicyclohexyl phthalate (DCHP) on the development of fetus and placenta in utero, pregnant rats were exposed to DHP or DCHP at dosages of 0, 20, 100, and 500 mg/kg bw/day, by gavage, on gestational days 6-19. Anogenital distance (AGD) and AGD-body weight ratio of female fetuses decreased in all treatment groups in a non-dose-response way. The ossification centers of bones and the intensity of Alizarin red stain of the fetuses decreased in all treatment groups. The white blood cell levels of fetuses in DHP and DCHP exposed groups increased at all dosages. Mean cell hemoglobin, hemoglobin concentrations, and hemoglobin levels of all DHP and DCHP treated male and female fetuses were reduced. Histopathologic changes (hemorrhage in labyrinth, degeneration of spongiotrophoblast, hemorrhage, decreased and irregular vessel formation, and edema in the basal zone) were observed in placentas at high dosages of DHP and DCHP. In contrast, there was no change in weight gain of dams in DHP and DCHP exposed groups compared to control, but resorption rate, reduced fetal weight, delayed ossification, placental disruption, and hematologic parameters clearly indicated that in utero DHP and DCHP exposure resulted in intrauterine growth retardation in rats.

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“…Ahbab et al (2015) found that in utero exposure to some phthalate esters (di-n-hexyl phthalate and DCHP) was associated with histological changes in the fetal testis, which presented atrophy, irregular seminiferous tubules, a reduced number or absence of germ cells and changes to the tubular walls, with the presence of multinucleated giant cells and irregular peritubular myoid cell distribution. The authors also found Leydig cell clusters of larger dimensions than those in unexposed controls [45]. Li et al subsequently reported similar findings in the testes of Sprague Dawley rat offspring whose mothers were administered DHEP orally during gestation [44].…”

Section: Pre-natal Exposure: Can Testicular Function Already Be Comprmentioning

confidence: 98%

“…Exposure to phthalate esters has also been associated with altered Sertoli cell adhesion to gonocytes [45,48]. Other histological abnormalities, such as the presence of multinucleated cells and abnormal peritubular myoid cell distribution, might also be related to the action of phthalate esters, which seem to trigger abnormal gonocyte cell division and changes to the seminiferous tubule structure [45]. The most interesting aspect seems to be changes to the Leydig cells and their interstitial distribution in clusters.…”

Section: Pre-natal Exposure: Can Testicular Function Already Be Comprmentioning

confidence: 99%

“…As fetal Leydig cells are not under pituitary control, paracrine factors secreted by the Sertoli cells seem to control their differentiation and function, and Leydig cell clusters could thus result from disrupted Sertoli cell function induced by exposure to phthalates. Alternatively, these clusters and the proliferation of fetal Leydig cells with a reduced volume and cytoplasm/nucleus ratio could compensate for the disrupted steroidogenesis induced by phthalate esters [45]. Exposure to phthalate esters (DBP) in pregnant Wistar rats seems to cause not only fetal cell dysfunction and, hence, reduced fetal intratesticular testosterone levels but also a reduction in the proliferation and function of adult Leydig cell precursors (which normally only differentiate on puberty), with normal or reduced blood testosterone concentrations and increased LH [49].…”

Section: Pre-natal Exposure: Can Testicular Function Already Be Comprmentioning

confidence: 99%

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Mechanisms of Testicular Disruption from Exposure to Bisphenol A and Phtalates

Pallotti

Pelloni

Gianfrilli

et al. 2020

JCM

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Great attention has been paid in recent years to the harmful effects of various chemicals that interfere with our natural hormone balance, collectively known as endocrine-disrupting chemicals (EDCs) or endocrine disruptors. The effects on the reproductive system of bisphenol A (BPA) and phthalates have received particular attention: while they have a short half-life, they are so widespread that human exposure can be considered as continuous. Evidence is often limited to the animal model, disregarding the likelihood of human exposure to a mixture of contaminants. Data from animal models show that maternal exposure probably has harmful effects on the male fetus, with an increased risk of urogenital developmental abnormalities. After birth, exposure is associated with changes in the hypothalamic-pituitary-testicular axis, hindering the development and function of the male genital pathways through the mediation of inflammatory mechanisms and oxidative stress. The epidemiological and clinical evidence, while generally confirming the association between reproductive abnormalities and some phthalate esters and BPA, is more contradictory, with wildly different findings. The aim of this review is therefore to provide an update of the potential mechanisms of the damage caused by BPA and phthalates to reproductive function and a review of the clinical evidence currently available in the literature.

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Influence of in utero di-n-hexyl phthalate and dicyclohexyl phthalate on fetal testicular development in rats

Cited by 25 publications

References 51 publications

Prenatal Exposure to Phthalates and the Development of Eczema Phenotypes in Male Children: Results from the EDEN Mother–Child Cohort Study

Prenatal Exposure to Phthalates and the Development of Eczema Phenotypes in Male Children: Results from the EDEN Mother–Child Cohort Study

Comparative developmental toxicity evaluation of di-n-hexyl phthalate and dicyclohexyl phthalate in rats

Mechanisms of Testicular Disruption from Exposure to Bisphenol A and Phtalates

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