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Exposure to di(2-ethylhexyl) phthalate and diisononyl phthalate during adulthood disrupts hormones and ovarian folliculogenesis throughout the prime reproductive life of the mouse.
Toxicology and Applied Pharmacology ( IF 3.3 ) Pub Date : 2020-03-10 , DOI: 10.1016/j.taap.2020.114952
Catheryne Chiang 1 , Lily R Lewis 1 , Grace Borkowski 1 , Jodi A Flaws 1
Affiliation  

Di(2-ethylhexyl) phthalate (DEHP) is a phthalate commonly used for its plasticizing capabilities. Because of the wide production and use of DEHP, humans are exposed to DEHP on a daily basis. Diisononyl phthalate (DiNP) is often used as a DEHP replacement chemical, and because of the increased use of DiNP, humans are increasingly exposed to DiNP over time. Of concern is that DEHP and DiNP both exhibit endocrine disrupting capabilities, and little is known about how short-term exposure to either of these phthalates affects aspects of female reproduction. Thus, this study tested the hypothesis that short-term exposure to DEHP or DiNP during adulthood has long-lasting consequences on ovarian follicles and hormones in female mice. Female CD-1 mice aged 39–40 days were orally dosed with either vehicle control (corn oil), DEHP (20 μg/kg/day–200 mg/kg/day), or DiNP (20 μg/kg/day–200 mg/kg/day) for 10 days. Ovarian follicle populations, estradiol, testosterone, progesterone, follicle stimulating hormone (FSH), and inhibin B were analyzed at time points immediately post-dosing and 3, 6, and 9 months post-dosing. The results indicate that 10 days of exposure to DEHP and DiNP changed the distribution of ovarian follicle populations and sex steroid hormones at multiple time points, including the last time point, 9 months post-dosing. Further, FSH was increased at multiple doses up to 6 months post-dosing. Inhibin B was not affected by treatment. These data show that short-term exposure to either DEHP or DiNP has long-term consequences that persist long after cessation of exposure.



中文翻译:

在成年期暴露于邻苯二甲酸二(2-乙基己基)邻苯二甲酸二(2-乙基己基)酯和邻苯二甲酸二异壬酯(diisononyl phthalate),会在小鼠的主要生殖寿命中破坏激素和卵巢的卵泡生成。

邻苯二甲酸二(2-乙基己基)酯(DEHP)是一种常用于增塑剂的邻苯二甲酸酯。由于DEHP的广泛生产和使用,人类每天都会接触DEHP。邻苯二甲酸二异壬酯(DiNP)通常用作DEHP替代化学品,并且由于DiNP的使用增加,随着时间的流逝,人类越来越多地暴露于DiNP。值得关注的是,DEHP和DiNP均具有内分泌干扰能力,而短期接触这两种邻苯二甲酸酯中的任何一种如何影响女性生殖方面则鲜为人知。因此,本研究检验了以下假设:成年期短期暴露于DEHP或DiNP对雌性小鼠的卵泡和激素具有长期的影响。对39至40天的雌性CD-1小鼠口服任一媒介物对照(玉米油),DEHP(20μg/ kg /天至200 mg / kg /天)或DiNP(20μg/ kg /天至200 mg / kg /天)持续10天。在给药后立即以及给药后3、6和9个月的时间点分析卵巢卵泡群体,雌二醇,睾丸激素,孕酮,卵泡刺激素(FSH)和抑制素B。结果表明,暴露于DEHP和DiNP的10天会在多个时间点(包括给药后9个月的最后一个时间点)改变卵巢卵泡种群和性类固醇激素的分布。此外,在给药后直至6个月内,多次剂量的FSH均升高。抑制素B不受治疗影响。这些数据表明,短期暴露于DEHP或DiNP具有长期后果,这种后果在停止暴露后仍会持续很长时间。在给药后立即以及给药后3、6和9个月的时间点分析睾丸激素,孕酮,促卵泡激素(FSH)和抑制素B。结果表明,暴露于DEHP和DiNP的10天会在多个时间点(包括给药后9个月的最后一个时间点)改变卵巢卵泡种群和性类固醇激素的分布。此外,在给药后直至6个月内,多次剂量的FSH均升高。抑制素B不受治疗影响。这些数据表明,短期暴露于DEHP或DiNP具有长期后果,这种后果在停止暴露后仍会持续很长时间。在给药后立即以及给药后3、6和9个月的时间点分析睾丸激素,孕酮,促卵泡激素(FSH)和抑制素B。结果表明,暴露于DEHP和DiNP的10天会在多个时间点(包括给药后9个月的最后一个时间点)改变卵巢卵泡种群和性类固醇激素的分布。此外,在给药后直至6个月,多次剂量的FSH增加。抑制素B不受治疗影响。这些数据表明,短期接触DEHP或DiNP具有长期后果,这种后果在停止接触后仍会持续很长时间。结果表明,暴露于DEHP和DiNP的10天会在多个时间点(包括给药后9个月的最后一个时间点)改变卵巢卵泡种群和性类固醇激素的分布。此外,在给药后直至6个月内,多次剂量的FSH均升高。抑制素B不受治疗影响。这些数据表明,短期暴露于DEHP或DiNP具有长期后果,这种后果在停止暴露后仍会持续很长时间。结果表明,暴露于DEHP和DiNP的10天会在多个时间点(包括给药后9个月的最后一个时间点)改变卵巢卵泡种群和性类固醇激素的分布。此外,在给药后直至6个月内,多次剂量的FSH均升高。抑制素B不受治疗影响。这些数据表明,短期接触DEHP或DiNP具有长期后果,这种后果在停止接触后仍会持续很长时间。

更新日期:2020-03-10
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