The causal role of endocrine disrupting chemicals in pubertal timing: a Mendelian randomization study.

IF 1 4区医学 Q4 ENDOCRINOLOGY & METABOLISM

Journal of Pediatric Endocrinology & Metabolism Pub Date : 2025-05-22 Print Date: 2025-07-28 DOI:10.1515/jpem-2025-0146

Melody Zuo, Isabel Gamache, Kaossarath Fagbemi, Felix R Day, Ken K Ong, Despoina Manousaki

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引用次数: 0

Abstract

Objectives: Endocrine disrupting chemicals (EDCs) interfere with hormonal homeostasis, and have been observationally linked to altered pubertal timing, defined by the age of menarche (AAM) in girls and the age at voice change (AVC) in boys. However, the causality of these associations remains unclear. We used Mendelian randomization (MR) to investigate if genetically altered serum EDC levels affect pubertal timing.

Methods: We performed univariate MR to assess the effects of 22 EDCs on AAM and AVC, using the largest GWAS for EDCs as well as European and multi-ethnic GWAS on AAM and AVC. Multivariate MR (MVMR) and two-step MR were conducted to examine mediating effects of body mass index (BMI).

Results: We found causal MR associations with AAM for three polychlorinated biphenyls (PCBs): PCB 74 (β_IVW: -0.015, 95 % CI [-0.028, -0.003], p=0.014), PCB 194 (β_IVW: -0.015, 95 % CI [-0.024, -0.007], p=3.27×10^-4), and PCB 206 (β_IVW: -0.024, 95 % CI [-0.041, -0.006], p=0.0068) and for dibutyl phthalate (DBP, β_IVW: 0.006, 95 % CI [0.001, 0.010], p=0.013). One MR association was found with AVC for bisphenol A (BPA, β_{Wald ratio}= -0.032, 95 % CI [-0.044, -0.019], p=2.62×10^-7). Mediation analyses by MVMR or Two-Step MR suggested BMI's mediating role in the associations of EDCs with AAM and AVC.

Conclusions: Our findings indicate that exposure to specific PCBs leads to earlier AAM whereas exposure to DBP delays AAM. Exposure to BPA leads to earlier AVC, with BMI potentially acting as a mediator.

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内分泌干扰化学物质在青春期时间中的因果作用：孟德尔随机研究。

目的：内分泌干扰化学物质（EDCs）干扰激素稳态，并已被观察到与青春期时间的改变有关，由女孩的月经初潮（AAM）年龄和男孩的变声年龄（AVC）定义。然而，这些关联的因果关系尚不清楚。我们使用孟德尔随机化（MR）来研究基因改变的血清EDC水平是否影响青春期时间。方法：我们采用单变量MR评估22种EDCs对AAM和AVC的影响，使用EDCs最大的GWAS以及欧洲和多种族的GWAS对AAM和AVC的影响。采用多变量磁共振（MVMR）和两步磁共振（two-step MR）来检验体重指数（BMI）的中介作用。结果：我们发现了三种多氯联苯（PCB）与AAM的因果MR关联：PCB 74 (βIVW: -0.015, 95 % CI [-0.028, -0.003], p=0.014), PCB 194 (βIVW: -0.015, 95 % CI [-0.024, -0.007], p=3.27×10-4), PCB 206 （βIVW: -0.024, 95 % CI [-0.041, -0.006], p=0.0068）和邻苯二甲酸二丁酯（DBP, βIVW: 0.006, 95 % CI [0.001, 0.010], p=0.013）。发现双酚A与AVC有MR相关性（BPA， βWald比= -0.032,95 % CI [-0.044, -0.019], p=2.62×10-7）。MVMR或Two-Step MR的中介分析表明BMI在EDCs与AAM和AVC的关联中起中介作用。结论：我们的研究结果表明，暴露于特定的多氯联苯会导致早期AAM，而暴露于DBP会延迟AAM。暴露于BPA会导致早期AVC， BMI可能是其中的中介。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Pediatric Endocrinology & Metabolism 医学-内分泌学与代谢

CiteScore

2.70

自引率

7.10%

发文量

176

审稿时长

3-6 weeks

期刊介绍： The aim of the Journal of Pediatric Endocrinology and Metabolism (JPEM) is to diffuse speedily new medical information by publishing clinical investigations in pediatric endocrinology and basic research from all over the world. JPEM is the only international journal dedicated exclusively to endocrinology in the neonatal, pediatric and adolescent age groups. JPEM is a high-quality journal dedicated to pediatric endocrinology in its broadest sense, which is needed at this time of rapid expansion of the field of endocrinology. JPEM publishes Reviews, Original Research, Case Reports, Short Communications and Letters to the Editor (including comments on published papers),. JPEM publishes supplements of proceedings and abstracts of pediatric endocrinology and diabetes society meetings.