Ministry of Education and Shanghai Key Laboratory of Children's Environmental Health, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Obstetrics and Gynecology, East Hospital, Tongji University School of Medicine, Shanghai, China.
Environ Pollut. 2018 Apr;235:446-452. doi: 10.1016/j.envpol.2017.12.095. Epub 2018 Jan 5.
Evidence has shown that leukocyte telomere length (LTL) at birth is related to the susceptibility to various diseases in later life and the setting of newborn LTL is influenced by the intrauterine environment. Perfluoroalkyl and polyfluoroalkyl substances (PFASs), as a kind of persistent organic pollutants, are commonly used in commercial and domestic applications and are capable of crossing the maternal-fetal barrier during pregnancy. We hypothesized that intrauterine exposure to PFASs may affect fetal LTL by increasing oxidative stress. To verify this hypothesis, LTL, concentrations of PFASs and reactive oxygen species (ROS) were measured in umbilical cord blood of 581 newborns from a prospective cohort. Our results showed that there were interactions between PFOS/PFDA and sex on LTL and ROS. The LTL was significantly shorter (0.926 ± 0.053 vs 0.945 ± 0.054, P = .023 for PFOS; 0.919 ± 0.063 vs 0.940 ± 0.059, P = .011 for PFDA) and the ROS levels were extremely higher (252.9 ± 60.5 [M] vs 233.5 ± 53.6 [M], P = .031 for PFOS; 255.2 ± 62.9 [M] vs 232.9 ± 58.3 [M], P = .011 for PFDA) in the female newborns whose PFOS or PFDA concentrations fell in the upmost quartile compared with those in the lowest quartile after adjusting for potential confounders. ROS levels were inversely associated with LTL in female newborns (β = -1.42 × 10, P = .022). 13% of the effect of PFOS on female LTL was mediated through ROS approximately by the mediation analyses. However, in male newborns, no relationships among PFASs, ROS and LTL were observed. Our findings suggest a "programming" role of PFASs on fetal telomere biology system in females in intrauterine stage.
已有证据表明,出生时白细胞端粒长度(LTL)与日后罹患各种疾病的易感性有关,而新生儿 LTL 的设定受宫内环境的影响。全氟烷基和多氟烷基物质(PFASs)作为一种持久性有机污染物,广泛应用于商业和家庭用途,并能在怀孕期间穿过母婴屏障。我们假设,PFASs 宫内暴露可能通过增加氧化应激而影响胎儿 LTL。为了验证这一假设,我们在一个前瞻性队列的 581 名新生儿脐带血中测量了 LTL、PFASs 浓度和活性氧(ROS)。我们的结果表明,PFOS/PFDA 与性别之间存在 LTL 和 ROS 的相互作用。LTL 明显缩短(PFOS:0.926±0.053 对 0.945±0.054,P=.023;PFDA:0.919±0.063 对 0.940±0.059,P=.011),ROS 水平极高(PFOS:252.9±60.5 [M] 对 233.5±53.6 [M],P=.031;PFDA:255.2±62.9 [M] 对 232.9±58.3 [M],P=.011),与潜在混杂因素调整后 PFOS 或 PFDA 浓度处于最高四分位数的女性新生儿相比,浓度处于最低四分位数的女性新生儿。ROS 水平与女性新生儿 LTL 呈负相关(β=-1.42×10,P=.022)。通过中介分析,PFOS 对女性 LTL 的影响有 13%是通过 ROS 介导的。然而,在男性新生儿中,PFASs、ROS 和 LTL 之间没有关系。我们的研究结果表明,PFASs 在宫内阶段对女性胎儿端粒生物学系统具有“编程”作用。