Department of Environmental Medicine, University of Southern Denmark, J.B. Winsløws Vej 17A, 5000, Odense C, Denmark; Department of Endocrinology, Odense University Hospital, Søndre Blvd. 29, Odense C, Denmark.
Department of Endocrinology, Odense University Hospital, Søndre Blvd. 29, Odense C, Denmark.
Environ Res. 2020 Mar;182:109101. doi: 10.1016/j.envres.2019.109101. Epub 2019 Dec 31.
Fetal programming of the endocrine system may be affected by exposure to perfluoroalkyl substances (PFAAs), as they easily cross the placental barrier. In vitro studies suggest that PFAAs may disrupt steroidogenesis. "Mini puberty" refers to a transient surge in circulating androgens, androgen precursors, and gonadotropins in infant girls and boys within the first postnatal months. We hypothesize that prenatal PFAA exposure may decrease the concentrations of androgens in mini puberty.
To investigate associations between maternal serum PFAA concentrations in early pregnancy and serum concentrations of androgens, their precursors, and gonadotropins during mini puberty in infancy.
In the prospective Odense Child Cohort, maternal pregnancy serum concentrations of five PFAAs: Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured at median gestational week 12 (IQR: 10, 15) in 1628 women. Among these, offspring serum concentrations of dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAS), androstenedione, 17-hydroxyprogesterone (17-OHP), testosterone, luteinizing (LH) and follicle stimulating hormones (FSH) were measured in 373 children (44% girls; 56% boys) at a mean age of 3.9 (±0.9 SD) months. Multivariate linear regression models were performed to estimate associations.
A two-fold increase in maternal PFDA concentration was associated with a reduction in DHEA concentration by -19.6% (95% CI: -32.9%, -3.8%) in girls. In girls, also, the androstenedione and DHEAS concentrations were decreased, albeit non-significantly (p < 0.11), with a two-fold increase in maternal PFDA concentration. In boys, no significant association was found between PFAAs and concentrations of androgens, their precursors, and gonadotropins during mini puberty.
Prenatal PFDA exposure was associated with significantly lower serum DHEA concentrations and possibly also with lower androstenedione and DHEAS concentrations in female infants at mini puberty. The clinical significance of these findings remains to be elucidated.
由于可轻易穿过胎盘屏障，全氟烷基物质（PFAAs）可能会影响胎儿内分泌系统的发育。体外研究表明，PFAAs 可能会破坏类固醇生成。“迷你青春期”是指婴儿在出生后最初几个月内循环中雄激素、雄激素前体和促性腺激素的短暂激增。我们假设产前 PFAA 暴露可能会降低迷你青春期的雄激素浓度。
探究妊娠早期母体血清 PFAA 浓度与婴儿迷你青春期时雄激素、其前体和促性腺激素浓度之间的关系。
在前瞻性的奥登塞儿童队列中，在 1628 名女性的妊娠中期 12 周（IQR：10，15）时测量了 5 种 PFAAs：全氟己烷磺酸（PFHxS）、全氟辛烷磺酸（PFOS）、全氟辛酸（PFOA）、全氟壬酸（PFNA）和全氟癸酸（PFDA）的妊娠血清浓度。在这些女性中，1628 名女性中有 373 名（44%为女孩；56%为男孩）的后代在平均 3.9 岁（±0.9 SD）时检测到脱氢表雄酮（DHEA）、硫酸脱氢表雄酮（DHEAS）、雄烯二酮、17-羟孕酮（17-OHP）、睾丸激素、促黄体生成素（LH）和卵泡刺激素（FSH）的血清浓度。采用多元线性回归模型来估计关联。
母体 PFDA 浓度增加两倍与女孩的 DHEA 浓度降低 19.6%（95%CI：-32.9%，-3.8%）相关。在女孩中，虽然与母体 PFDA 浓度增加两倍相关的雄激素前体雄烯二酮和 DHEAS 浓度降低，但无统计学意义（p < 0.11）。在男孩中，未发现 PFAA 与迷你青春期时雄激素、其前体和促性腺激素浓度之间存在显著关联。
产前 PFDA 暴露与女婴迷你青春期时血清 DHEA 浓度显著降低有关，并且可能还与较低的雄烯二酮和 DHEAS 浓度有关。这些发现的临床意义仍有待阐明。
