1.有机磷和拟除虫菊酯类农药暴露对育龄期女性生育力的影响:基于上海优生儿童队列的研究
研究依托上海优生儿童队列招募正在备孕的育龄期女性,收集尿液样本进行有机磷(organophosphates, OPs)和拟除虫菊酯(pyrethroids, PYRs)尿液代谢产物的检测,通过一年的前瞻性电话随访并收集女性的备孕时间(Time to pregnancy, TTP)及怀孕情况。研究共纳入615名女性,OPs和PYRs主要代谢产物的检出率均>90%。本研究首次提供人群研究证据,提示育龄期女性OP和PYR暴露普遍,OP和PYR暴露可能引起女性的生育力下降,表现为TTP延长和不孕风险增加且影响在未生育过的女性中更为显著。
2.孕前妇女血浆全氟烷基、多氟烷基类物质浓度与月经周期特征
全氟烷基和多氟烷基物质(PFASs)是一种持久性的合成化学物质,广泛应用于工业领域,经常在人体中检测到。在大鼠中,PFASs可干扰发情周期。在人类中,月经被认为是女性生育能力的代表,周期性月经在没有怀孕的子宫内膜脱落和胚胎植入准备中起着关键作用。本研究发现孕前妇女中自述月经周期不规则多于高检测出浓度的PFOA、PFOS、PFNA、PFHxS有关,因此某些PFASs女性月经异常存在关联。
3. 孕期全氟和多氟烷基化合物暴露增加孕期睡眠障碍风险
基于上海优生儿童队列,本研究在3526名接受了孕早期(9~16周)血浆10种PFAS检测(UPLC-MS/MS)的妇女中,分别纳入3174、3070和 2887 名参与了妊娠早期、中期和晚期匹兹堡睡眠质量指数(PSQI) 问卷评估的孕妇。单一污染物分析表明,大多数 PFAS 与各孕期睡眠障碍风险增加、睡眠效率降低和睡眠持续时间缩短有关。其中,PFBS与孕早、中期夜醒次数增加呈正向关联。WQS 模型揭示了 PFAS 混合物与孕妇睡眠质量降低(PSQI>5分)风险升高之间存在显著关联。GEE 分析表明,PFAS 暴露与各孕期睡眠障碍的风险增加相关,包括主观睡眠质量较差、睡眠时间较短、睡眠效率较低、打鼾、睡眠药物的使用。研究首次表明,PFAS暴露与孕期睡眠障碍风险增加显著相关。对睡眠质量的影响,PFBS 在孕早期和中期发挥主导作用,而 PFOS 是孕晚期的主要作用因子。
4. 全氟化合物暴露对妊娠期糖尿病及糖稳态影响的前瞻性研究
研究探讨了孕早期全氟化合物暴露与孕晚期妊娠期糖尿病及糖稳态的关系,依托上海优生儿童队列,共纳入2474名孕妇。结果显示,研究人群中PFAS暴露主要以PFOA和PFOS为主。研究结果提示孕期PFAS暴露与GDM 风险增加和血糖稳态失调有关。PFOS、PFNA 和 PFHpA 可能在 PFAS 的代谢毒性作用中发挥重要作用,且PFAS暴露对孕前体重正常的女性影响更为明显。
5.胎盘源性MHC I类链相关基因A的遗传变异增加了中国人群早产的风险
早产(PTB)是全球新生儿死亡率和发病率的主要因素。然而,PTB的病理生理过程尚不清楚。研究对胎盘源性MHC I类链相关基因A(MICA)中单核苷酸多态性(SNP)可能干扰胎盘发育从而导致PTB的假设进行了验证。在这项中国汉族的127名早产儿和634名足月儿的病例对照研究中,对MICA中19个选定的单核苷酸多态性进行了基因分型。发现rs2256318变异体的纯合子与PTB风险的显著增加相关(与g/g基因型相比,a/a的校正比值比为6.97,95%置信区间为2.34-20.74,p=0.001)。此外,rs2256318的a/a基因型与新生儿胎盘重量下降有关(β=-25.331;p=0.033)。进一步分层分析显示,在女性人群中,rs2256318的A/A基因型与PTB风险增加相关。同时,我们观察到多态性rs2516448与性别之间的存在交互作用(P = 0.04)。病例与对照组中单倍型的分布无显著性差异。我们的结果表明,MICA中rs2256318的多态性可能通过干扰胎盘发育而导致PTB。这些发现需要在更大人群及多种族人群中进一步的验证。
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