Perez Cynthia, Sehgal Neha, Eick Stephanie M, Barr Dana Boyd, Panuwet Parinya, Yakimavets Volha, Chen Kelsey, Shankar Kartik, Pearson Kevin J, Andres Aline, Everson Todd M
Gangarosa Department of Environmental Health, Emory University Rollins School of Public Health, Atlanta, GA, USA.
Gangarosa Department of Environmental Health, Emory University Rollins School of Public Health, Atlanta, GA, USA; Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA.
Environ Res. 2025 Apr 1;270:120868. doi: 10.1016/j.envres.2025.120868. Epub 2025 Jan 28.
Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants that may impact placental function, and potentially gestational age acceleration (GAA), a deviation from reported and predicted gestational age. GAA potentially represents differences in cell maturation in response to a challenging environment.
This study aimed to characterize the effects of individual and mixtures of PFAS on GAA, cell composition, birth length, and birthweight.
Pregnant peoples were recruited from around Little Rock, Arkansas, United States between 2011 and 2014. We utilized placental DNA methylation profiles of 153 healthy pregnancies to calculate GAA and estimate the proportions of six placental cell types. PFAS were quantified in homogenized placental tissue using high-performance liquid chromatography-tandem mass spectrometry. Five PFAS were detected in over 70% of samples. We studied these five PFAS individually using multiple linear regression and as a mixture using quantile g-computation, while adjusting for confounders. The dependent variables in our models included GAA, cell proportions, birthweight, and birth length.
We did not observe associations between PFAS and any of our outcomes in our primary models. While GAA in male placentas were not significantly affected by PFAS, the PFAS mixture associated with decreased syncytiotrophoblast proportion (Ψ = -0.018, 95% CI [-0.032, -0.004]). PFAS mixture did not alter cell proportions in female placentas but was associated with increased GAA (Ψ = 0.269, 95% CI [0.026, 0.513]). Similarly, for females, greater GAA was associated with PFOA (β = 0.141, 95% CI [-0.016,0.040]) and PFOS (β = 0.205, 95% CI [-0.020,0.0416]).
We illustrate that PFAS may influence placental development in a sex specific manner. Suggested by decrease in syncytotrophoblast, male placenta may experience a more stunted development due to PFAS exposure. Alternatively, female placentas exhibited increased GAA, a plausible marker of elevated developmental maturation in the face of environmental adversity.
全氟和多氟烷基物质（PFAS）是持久性有机污染物，可能影响胎盘功能，并可能导致胎龄加速（GAA），即与报告和预测的胎龄存在偏差。GAA可能代表细胞在挑战性环境中成熟的差异。
本研究旨在描述PFAS个体及混合物对GAA、细胞组成、出生身长和出生体重的影响。
2011年至2014年期间，从美国阿肯色州小石城周边招募孕妇。我们利用153例健康妊娠的胎盘DNA甲基化谱来计算GAA，并估计六种胎盘细胞类型的比例。使用高效液相色谱-串联质谱法对匀浆后的胎盘组织中的PFAS进行定量。在超过70%的样本中检测到五种PFAS。我们分别使用多元线性回归研究这五种PFAS，并使用分位数g计算法将其作为混合物进行研究，同时对混杂因素进行调整。我们模型中的因变量包括GAA、细胞比例、出生体重和出生身长。
在我们的主要模型中，未观察到PFAS与我们的任何结果之间存在关联。虽然男性胎盘的GAA不受PFAS的显著影响，但PFAS混合物与合体滋养层比例降低有关（Ψ = -0.018，95%置信区间[-0.032，-0.004]）。PFAS混合物未改变女性胎盘的细胞比例，但与GAA增加有关（Ψ = 0.269，95%置信区间[0.026，0.513]）。同样，对于女性而言，较高的GAA与全氟辛酸（PFOA）（β = 0.141，95%置信区间[-0.016，0.040]）和全氟辛烷磺酸（PFOS）（β = 0.205，95%置信区间[-0.020，0.0416]）有关。
我们表明PFAS可能以性别特异性方式影响胎盘发育。合体滋养层减少表明，男性胎盘可能因接触PFAS而发育更为迟缓。或者，女性胎盘的GAA增加，这可能是面对环境逆境时发育成熟度提高的一个合理标志。
