Transgenerational effects of polychlorinated biphenyls: 1. Development and physiology across 3 generations of rats.
Transgenerational effects of polychlorinated biphenyls: 1. Development and physiology across 3 generations of rats.
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DOI：
10.1186/s12940-018-0362-5
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发表时间：
2018-02-20
期刊：
影响因子：
--
通讯作者：
Gore AC
中科院分区：
文献类型：
--
作者：
Mennigen JA;Thompson LM;Bell M;Tellez Santos M;Gore AC
多氯联苯（PCBs）是一种持久性有机环境污染物，也是已知的内分泌干扰物。以前的研究表明，发育暴露于弱雌激素PCB混合物Aroclor 1221（A1221）在Sprague-Dawley大鼠改变性发育，成年生殖生理和体重。目前的研究测试了这样一个假设，即产前A1221暴露不仅会破坏暴露个体（F1代）寿命内的这些终点，而且还可能影响后代（F2-F3）。我们在胚胎（E）16和E18天用A1221（1 mg/kg）、苯甲酸雌二醇（50 μg/kg，阳性雌激素对照）或溶剂（3% DMSO的芝麻油溶液，阴性对照）处理妊娠雌性大鼠。在F1、F2和F3代中，测量与生殖和发育生理学的性二态发育轨迹相关的终点，并评估成年后的生殖内分泌状态。发现跨代内分泌干扰物对体重和血清激素有显著影响。A1221后代在整个出生后发育过程中的F2-母体谱系中体重显著较高，断奶后的F3-母体谱系动物体重显著较高。在女性中，世代和谱系特定的影响暴露于血清孕酮和雌二醇。具体而言，与相应的F2和F3溶剂对应动物相比，F2-A1221雌性动物的血清孕酮浓度较低，F3-A1221雌性动物的血清孕酮浓度较高。F3-A1221中的血清雌二醇浓度高于F3溶剂组雌性动物。生殖和肾上腺器官重量，出生结局，性别比和发情周期，不受影响。值得注意的是，A1221的作用有时仅通过雌激素对照EB反映，表明A1221的作用机制可能是通过非雌激素途径。多氯联苯对大鼠的体重和激素产生了影响，这种影响在直接接触的F1后代中没有观察到，但在F2和F3代中出现了。此外，大多数影响发生在母体谱系中;这可能与E16和18时F1胎仔的暴露时间有关，此时生殖系（未来F2代）表观遗传变化在性别中存在差异。这些结果表明，内分泌干扰物的跨代影响对人类有影响，因为我们现在是自世纪中期化学革命以来的第三代，甚至被禁止的化学品，如多氯联苯，对我们后代的健康有持久的影响。本文的在线版本（10.1186/s12940-018-0362-5）包含补充材料，可供授权用户使用。
Polychlorinated biphenyls (PCBs) are persistent organic environmental contaminants and known endocrine-disrupting chemicals (EDCs). Previous studies demonstrated that developmental exposure to the weakly estrogenic PCB mixture Aroclor 1221 (A1221) in Sprague-Dawley rats altered sexual development, adult reproductive physiology and body weight. The current study tested the hypothesis that prenatal A1221 exposure not only disrupts these endpoints within an exposed individual’s (F1 generation) lifespan, but may also affect subsequent generations (F2-F3). We treated pregnant female rats on embryonic days (E) 16 and E18 with A1221 (1 mg/kg), estradiol benzoate (50 μg/kg, positive estrogenic control), or vehicle (3% DMSO in sesame oil, negative control). Endpoints related to sexually dimorphic developmental trajectories of reproductive and developmental physiology were measured, and as adults, reproductive endocrine status was assessed, in the F1, F2, and F3 generations. Significant effects of transgenerational EDCs were found for body weight and serum hormones. The A1221 descendants had significantly higher body weight in the F2-maternal lineage throughout postnatal development, and in F3-maternal lineage animals after weaning. In females, generation- and lineage-specific effects of exposure were found for serum progesterone and estradiol. Specifically, serum progesterone concentrations were lower in F2-A1221 females, and higher in F3-A1221 females, compared to their respective F2- and F3-vehicle counterparts. Serum estradiol concentrations were higher in F3-A1221 than F3-vehicle females. Reproductive and adrenal organ weights, birth outcomes, sex ratio, and estrous cycles, were unaffected. It is notable that effects of A1221 were only sometimes mirrored by the estrogenic control, EB, indicating that the mechanism of action of A1221 was likely via non-estrogenic pathways. PCBs caused body weight and hormonal effects in rats that were not observed in the directly exposed F1 offspring, but emerged in F2 and F3 generations. Furthermore, most effects were in the maternal lineage; this may relate to the timing of exposure of the F1 fetuses at E16 and 18, when germline (the future F2 generation) epigenetic changes diverge in the sexes. These results showing transgenerational effects of EDCs have implications for humans, as we are now in the 3rd generation since the Chemical Revolution of the mid-twentieth century, and even banned chemicals such as PCBs have a persistent imprint on the health of our descendants. The online version of this article (10.1186/s12940-018-0362-5) contains supplementary material, which is available to authorized users.
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影响因子：
10.4
作者：
Alonso-Magdalena P;Vieira E;Soriano S;Menes L;Burks D;Quesada I;Nadal A
通讯作者：
Nadal A
一项队列研究显示，在子宫内接触多氯联苯与密歇根雌性食鱼者的女儿的生育能力下降有关。
DOI：
10.1186/s12940-016-0175-3
发表时间：
2016-08-31
期刊：
Environmental health : a global access science source
影响因子：
--
作者：
Han L;Hsu WW;Todem D;Osuch J;Hungerink A;Karmaus W
通讯作者：
Karmaus W
大脑性别差异的表观遗传学。
影响因子：
5.3
作者：
McCarthy, Margaret M.;Auger, Anthony P.;Bale, Tracy L.;De Vries, Geert J.;Dunn, Gregory A.;Forger, Nancy G.;Murray, Elaine K.;Nugent, Bridget M.;Schwarz, Jaclyn M.;Wilson, Melinda E.
通讯作者：
Wilson, Melinda E.
影响因子：
2.8
作者：
Ghosh, Somiranjan;Murinova, Lubica;Dutta, Sisir K.
通讯作者：
Dutta, Sisir K.
影响因子：
3.5
作者：
Gillette R;Reilly MP;Topper VY;Thompson LM;Crews D;Gore AC
通讯作者：
Gore AC