PMID- 28800472 OWN - NLM STAT- MEDLINE DCOM- 20171016 LR - 20181113 IS - 1096-0953 (Electronic) IS - 0013-9351 (Print) IS - 0013-9351 (Linking) VI - 159 DP - 2017 Nov TI - Phthalate and bisphenol A exposure during in utero windows of susceptibility in relation to reproductive hormones and pubertal development in girls. PG - 143-151 LID - S0013-9351(17)30910-6 [pii] LID - 10.1016/j.envres.2017.07.051 [doi] AB - BACKGROUND: Over the past several decades, the age of pubertal onset in girls has shifted downward worldwide. As early pubertal onset is associated with increased risky behavior and psychological issues during adolescence and cardiometabolic disease and cancer in adulthood, this is an important public health concern. Exposure to endocrine disrupting chemicals during critical windows of in utero development may play a role in this trend. Our objective was to investigate trimester-specific phthalate and BPA exposure in relation to pubertal development among girls in the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort. METHODS: We measured maternal urinary phthalate metabolites and BPA in samples collected during the first, second, and third trimesters of pregnancy. To assess reproductive development among their female children, we measured serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG), and assessed sexual maturation, including Tanner staging for breast and pubic hair development and menarche status, at age 8-13 years (n = 120). We used linear and logistic regression to examine measures of trimester-specific in utero exposure as predictors of peripubertal hormone levels and pubertal onset, respectively. In secondary analyses, we evaluated estimated exposure at the midpoint of the first trimester and rates of change in exposure across pregnancy in relation to outcomes. RESULTS: Several phthalate metabolites measured throughout in utero development were associated with higher serum testosterone concentrations, while a number of metabolites measured in the third trimester were associated with higher DHEA-S. For example, an interquartile range (IQR) increase in mean monoethyl phthalate (MEP) levels across pregnancy was associated with 44% higher peripubertal testosterone (95% CI: 13-83%), while an IQR increase in di-2-ethylhexyl phthalate metabolites (SigmaDEHP) specifically in the third trimester was associated with 25% higher DHEA-S (95%CI: 4.7-47%). In IQR increase in mean mono-2-ethylhexyl phthalate (MEHP) levels across pregnancy was associated with lower odds of having a Tanner Stage >1 for breast development (OR = 0.32, 95%CI: 0.11-0.95), while MEHP in the third trimester was associated with higher odds of having a Tanner Stage >1 for pubic hair development (OR = 3.76, 95%CI: 1.1-12.8). Results from secondary analyses were consistent with findings from our main analysis. CONCLUSION: These findings suggest that female reproductive development may be more vulnerable to the effects of phthalate or BPA exposure during specific critical periods of in utero development. This highlights the need for comprehensive characterizations of in utero exposure and consideration of windows of susceptibility in developmental epidemiological studies. Future research should consider repeated measures of in utero phthalate and BPA exposure within each trimester and across pregnancy. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Watkins, Deborah J AU - Watkins DJ AD - Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA. Electronic address: debjwat@umich.edu. FAU - Sanchez, Brisa N AU - Sanchez BN AD - Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA. FAU - Tellez-Rojo, Martha Maria AU - Tellez-Rojo MM AD - Center for Nutrition and Health Research, Instituto Nacional de Salud Publica, Cuernavaca, MOR, Mexico. FAU - Lee, Joyce M AU - Lee JM AD - Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA; Pediatric Endocrinology, Child Health Evaluation and Research Unit (CHEAR), University of Michigan, Ann Arbor, MI, USA. FAU - Mercado-Garcia, Adriana AU - Mercado-Garcia A AD - Center for Nutrition and Health Research, Instituto Nacional de Salud Publica, Cuernavaca, MOR, Mexico. FAU - Blank-Goldenberg, Clara AU - Blank-Goldenberg C AD - American British Cowdray (ABC) Hospital, Mexico City, Mexico. FAU - Peterson, Karen E AU - Peterson KE AD - Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA; Center for Human Growth and Development, University of Michigan, Ann Arbor, MI, USA. FAU - Meeker, John D AU - Meeker JD AD - Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA. LA - eng GR - P01 ES022844/ES/NIEHS NIH HHS/United States GR - P30 DK092926/DK/NIDDK NIH HHS/United States GR - P30 ES017885/ES/NIEHS NIH HHS/United States GR - T32 ES007062/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20170808 PL - Netherlands TA - Environ Res JT - Environmental research JID - 0147621 RN - 0 (Benzhydryl Compounds) RN - 0 (Endocrine Disruptors) RN - 0 (Environmental Pollutants) RN - 0 (Phenols) RN - 0 (Phthalic Acids) RN - 6O7F7IX66E (phthalic acid) RN - MLT3645I99 (bisphenol A) SB - IM MH - Adolescent MH - Benzhydryl Compounds/*toxicity MH - Child MH - Endocrine Disruptors/*toxicity MH - *Environmental Exposure MH - Environmental Pollutants/*toxicity MH - Female MH - Humans MH - Longitudinal Studies MH - Mexico MH - Phenols/*toxicity MH - Phthalic Acids/*toxicity MH - Pregnancy MH - Sexual Maturation/*drug effects PMC - PMC5623649 MID - NIHMS898716 OTO - NOTNLM OT - Adrenarche OT - Bisphenol A OT - In utero OT - Phthalates OT - Pregnancy OT - Puberty OT - Windows of susceptibility EDAT- 2017/08/12 06:00 MHDA- 2017/10/17 06:00 PMCR- 2018/11/01 CRDT- 2017/08/12 06:00 PHST- 2017/05/15 00:00 [received] PHST- 2017/06/28 00:00 [revised] PHST- 2017/07/30 00:00 [accepted] PHST- 2017/08/12 06:00 [pubmed] PHST- 2017/10/17 06:00 [medline] PHST- 2017/08/12 06:00 [entrez] PHST- 2018/11/01 00:00 [pmc-release] AID - S0013-9351(17)30910-6 [pii] AID - 10.1016/j.envres.2017.07.051 [doi] PST - ppublish SO - Environ Res. 2017 Nov;159:143-151. doi: 10.1016/j.envres.2017.07.051. Epub 2017 Aug 8.