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In utero DDT exposure and breast density in early menopause by maternal history of breast cancer.

ABSTRACT: We examined the relationship between intrauterine dichlorodiphenyltrichloroethane (DDT) exposure (o,p'-DDT, p,p'-DDT, and p,p'-DDE) and mammographic breast density (MBD) in midlife, one of the strongest risk factors for breast cancer. We focused our analyses on o,p'-DDT exposure given our previous report of a positive association between intrauterine o,p'-DDT exposure and daughter's breast cancer (BC) risk. Here we estimated associations of intrauterine serum DDTs with MBD in 224 daughters of women in the Child Health and Development Studies pregnancy cohort whose mothers did not develop BC (MBCa-) and 156 daughters whose mothers did develop BC (MBCa+). In MBCa+?daughters, highest relative to lowest quartile of o,p'-DDT exposure was associated with a 17-unit higher dense area (95% CI?=?2.6-31.2; P_trend?=?0.01). We did not observe an association between o,p'-DDT and density measures in MBCa- daughters. MBD, an intermediate marker of BC risk, may be affected by intrauterine DDT exposures; MBCa status may modify the association.

SUBMITTER: McDonald JA

PROVIDER: S-EPMC7018589 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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In utero DDT exposure and breast density in early menopause by maternal history of breast cancer.

McDonald Jasmine A JA Cirillo Piera M PM Tehranifar Parisa P Krigbaum Nickilou Y NY Engmann Natalie J NJ Cohn Barbara A BA Terry Mary Beth MB

Reproductive toxicology (Elmsford, N.Y.) 20190814

We examined the relationship between intrauterine dichlorodiphenyltrichloroethane (DDT) exposure (o,p'-DDT, p,p'-DDT, and p,p'-DDE) and mammographic breast density (MBD) in midlife, one of the strongest risk factors for breast cancer. We focused our analyses on o,p'-DDT exposure given our previous report of a positive association between intrauterine o,p'-DDT exposure and daughter's breast cancer (BC) risk. Here we estimated associations of intrauterine serum DDTs with MBD in 224 daughters of wo ...[more]

PMID: 31421228

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Project description:Aim/hypothesis:In utero exposure to maternal diabetes increases the risk of developing hypertension and cardiovascular disorders during adulthood. We have previously shown that this is associated with changes in vascular tone in favor of a vasoconstrictor profile, which is involved in the development of hypertension. This excessive constrictor tone has also a strong impact on vascular structure. Our objective was to study the impact of in utero exposure to maternal diabetes on vascular structure and remodeling induced by chronic changes in hemodynamic parameters. Methods and Results: We used an animal model of rats exposed in utero to maternal hyperglycemia (DMO), which developed hypertension at 6 months of age. At a pre-hypertensive stage (3 months of age), we observed deep structural modifications of the vascular wall without any hemodynamic perturbations. Indeed, in basal conditions, resistance arteries of DMO rats are smaller than those of control mother offspring (CMO) rats; in addition, large arteries like thoracic aorta of DMO rats have an increase of smooth muscle cell attachments to elastic lamellae. In an isolated perfused kidney, we also observed a leftward shift of the flow/pressure relationship, suggesting a rise in renal peripheral vascular resistance in DMO compared to CMO rats. In this context, we studied vascular remodeling in response to reduced blood flow by in vivo mesenteric arteries ligation. In DMO rats, inward remodeling induced by a chronic reduction in blood flow (1 or 3 weeks after ligation) did not occur by contrast to CMO rats in which arterial diameter decreased from 428 ± 17 ?m to 331 ± 20 ?m (at 125 mmHg, p = 0.001). In these animals, the transglutaminase 2 (TG2) pathway, essential for inward remodeling development in case of flow perturbations, was not activated in low-flow (LF) mesenteric arteries. Finally, in old hypertensive DMO rats (18 months of age), we were not able to detect a pressure-induced remodeling in thoracic aorta. Conclusions: Our results demonstrate for the first time that in utero exposure to maternal diabetes induces deep changes in the vascular structure. Indeed, the early narrowing of the microvasculature and the structural modifications of conductance arteries could be a pre-emptive adaptation to fetal programming of hypertension.

Project description:Dichlorodiphenyltrichloroethane (DDT), polybrominated diphenyl ether (PBDE) flame retardants, and polychlorinated biphenyls (PCBs) are believed to be endocrine-disrupting chemicals (EDCs) in humans and animals. The purpose of this study is to examine the relationship of in utero and childhood exposure to these purported EDCs and reproductive hormones in adolescent boys who participated in CHAMACOS, an ongoing birth cohort in California's Salinas Valley. We measured o,p'- and p,p'-DDT, p,p'-DDE, PBDEs and PCBs in serum collected from mothers during pregnancy or at delivery and from their sons at 9 years. We measured concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone (T) from 234 of their sons at 12 years. In adjusted models, we found that a 10-fold increase in maternal prenatal serum concentrations of BDE-153 was associated with a 22.2% increase (95% CI: 1.0, 47.9) in FSH, a 96.6% increase (95% CI: 35.7, 184.7) in LH, and a 92.4% increase (95% CI: 20.9, 206.2) increase in T. Similarly, BDE-100 concentrations were associated with increases in boys' LH levels. A 10-fold increase in total prenatal ΣPCBs was associated with a 64.5% increase (95% CI: 8.6, 149.0) in FSH, primarily driven by non- dioxin-like congeners. Boys' hormone levels were only marginally associated with prenatal DDT or DDE in primary models, but when boys' Tanner stage at age 12 was added to models, prenatal maternal DDT levels were associated with decreases in LH (adjusted percent change per 10-fold increase=-18.5%, 95% CI: -29.8, -5.4) and T (percent change=-18.2%, 95% CI: -30.2, -4.2) and DDE with LH (percent change=-18.3%, 95% CI: -32.9, -0.6). Exposures measured in the children's serum at 9 years also showed associations between BDE-153 and ΣPCBs. However, there is evidence that these associations appear to be mediated by child BMI. This study suggests associations on male hormones of 12year old boys related to exposure to certain EDC exposure prenatally. The implications on future reproductive function in puberty and adulthood should be determined.

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In utero DDT exposure and breast density in early menopause by maternal history of breast cancer.

Publications

In utero DDT exposure and breast density in early menopause by maternal history of breast cancer.

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