PMID- 31421446 OWN - NLM STAT- MEDLINE DCOM- 20191003 LR - 20201001 IS - 1096-0953 (Electronic) IS - 0013-9351 (Print) IS - 0013-9351 (Linking) VI - 177 DP - 2019 Oct TI - In utero and peripubertal metals exposure in relation to reproductive hormones and sexual maturation and progression among girls in Mexico City. PG - 108630 LID - S0013-9351(19)30427-X [pii] LID - 10.1016/j.envres.2019.108630 [doi] AB - There is increasing evidence that several metals are endocrine disrupting chemicals (EDCs). In utero development and adolescence are critical windows of susceptibility to EDC exposure. With the exception of a few heavy metals, few human studies have evaluated the impact of metal exposure on pubertal development. Our aim was to investigate measures of in utero and peripubertal metal exposure in relation to reproductive hormone levels and sexual maturation and progression among girls from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohorts. We measured urinary concentrations of aluminum (Al), arsenic (As), barium (Ba), cadmium (Cd), cobalt (Co), copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), nickel (Ni), antimony (Sb), selenium (Se), and zinc (Zn) in samples collected from women during their third trimester of pregnancy and from their female children at 8-13 years (n = 132). We measured serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG) at age 8-13, and assessed Tanner stages for sexual maturation (breast, pubic hair development, and menarche status), at two time points (8-13, 14-18 years). We used linear regression to independently examine in utero and peripubertal metal concentrations as predictors of peripubertal hormones. In a longitudinal analysis using generalized estimation equations, we evaluated Tanner stage and menarche progression in relation to individual in utero and peripubertal metal concentrations. We found that higher in utero Zn was associated with increased inhibin B. Several metals at 8-13 years were associated with higher DHEA-S and estradiol, while Ni was positively but Cu was negatively associated with testosterone. In utero Ni, Al, and Cd were associated with slower progression of breast development after adjustment for child age and BMI z-score. For example, an IQR increase in in utero Al exposure was associated with 0.82 times lower odds of progressing to a higher Tanner stage for breast development per year (95% CI: 0.68, 0.99). Peripubertal concentrations of Ba and Al were also associated with being at a higher pubic hair Tanner stage and menarche at 8-13, but lower odds of progressing to the next stage at 14-18 years. We used Bayesian kernel machine regression (BKMR) to model the joint effect of multiple metals while accounting for correlated exposures, as well as potential non-linear relationships between metals and outcomes of interest, which yielded results similar to individual analyses. These findings suggest that female reproductive development may be vulnerable to the effects of metal exposure, and using both Tanner stages and hormone levels may provide clues about underlying mechanisms in two sensitive periods of development. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Ashrap, Pahriya AU - Ashrap P AD - Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, United States. FAU - Sanchez, Brisa N AU - Sanchez BN AD - Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, United States. FAU - Tellez-Rojo, Martha M AU - Tellez-Rojo MM AD - Center for Nutrition and Health Research, Instituto Nacional de Salud Publica, Cuernavaca, Morelos, Mexico. FAU - Basu, Niladri AU - Basu N AD - Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, Quebec, Canada. FAU - Tamayo-Ortiz, Marcela AU - Tamayo-Ortiz M AD - Center for Nutrition and Health Research, Instituto Nacional de Salud Publica, Cuernavaca, Morelos, Mexico; Mexican Council for Science and Technology, 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, United States. FAU - Meeker, John D AU - Meeker JD AD - Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, United States. FAU - Watkins, Deborah J AU - Watkins DJ AD - Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, United States. Electronic address: debjwat@umich.edu. LA - eng GR - T42 OH008455/OH/NIOSH CDC HHS/United States GR - P20 ES018171/ES/NIEHS NIH HHS/United States GR - R01 ES007821/ES/NIEHS NIH HHS/United States GR - P01 ES022844/ES/NIEHS NIH HHS/United States GR - P30 ES017885/ES/NIEHS NIH HHS/United States PT - Journal Article DEP - 20190808 PL - Netherlands TA - Environ Res JT - Environmental research JID - 0147621 RN - 0 (Endocrine Disruptors) RN - 0 (Gonadal Steroid Hormones) RN - 0 (Metals, Heavy) RN - 0 (Sex Hormone-Binding Globulin) RN - 0 (inhibin B) RN - 3XMK78S47O (Testosterone) RN - 4TI98Z838E (Estradiol) RN - 57285-09-3 (Inhibins) RN - 57B09Q7FJR (Dehydroepiandrosterone Sulfate) SB - IM MH - Adolescent MH - Bayes Theorem MH - Child MH - Cities MH - Dehydroepiandrosterone Sulfate/blood MH - Endocrine Disruptors/*adverse effects/urine MH - Estradiol/blood MH - Female MH - Gonadal Steroid Hormones/*blood MH - Humans MH - Inhibins/blood MH - Metals, Heavy/*adverse effects/urine MH - Mexico MH - Pregnancy MH - Prenatal Exposure Delayed Effects/*epidemiology MH - Sex Hormone-Binding Globulin/analysis MH - *Sexual Maturation MH - Testosterone/blood PMC - PMC6734930 MID - NIHMS1537495 OTO - NOTNLM OT - Hormone OT - In utero exposure OT - Metal OT - Pregnancy OT - Puberty COIS- Competing interests The authors declare that they have no competing interests. EDAT- 2019/08/20 06:00 MHDA- 2019/10/08 06:00 PMCR- 2020/10/01 CRDT- 2019/08/18 06:00 PHST- 2019/05/05 00:00 [received] PHST- 2019/07/23 00:00 [revised] PHST- 2019/08/04 00:00 [accepted] PHST- 2019/08/20 06:00 [pubmed] PHST- 2019/10/08 06:00 [medline] PHST- 2019/08/18 06:00 [entrez] PHST- 2020/10/01 00:00 [pmc-release] AID - S0013-9351(19)30427-X [pii] AID - 10.1016/j.envres.2019.108630 [doi] PST - ppublish SO - Environ Res. 2019 Oct;177:108630. doi: 10.1016/j.envres.2019.108630. Epub 2019 Aug 8.