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Independent and combined effects of Bisphenol A and Diethylhexyl Phthalate on gestational outcomes and offspring development in Sprague-Dawley rats
Chemosphere ( IF 8.8 ) Pub Date : 2020-09-14 , DOI: 10.1016/j.chemosphere.2020.128307
Josephine Bou Dagher , Coral K. Hahn-Townsend , Amrita Kaimal , Maryam Al Mansi , Joseph E. Henriquez , Diane G. Tran , Christian R. Laurent , Caleb J. Bacak , Hannah E. Buechter , Celexis Cambric , Jared Spivey , Yen-Jun Chuang , Elyssa J. Campbell , Abhyuday Mandal , Puliyur S. Mohankumar , Sheba M.J. MohanKumar

Bisphenol A (BPA) and Diethylhexyl Phthalate (DEHP) are well-studied endocrine disrupting chemicals (EDCs), however, the effects of mixtures of these EDCs are not. To assess the consequences of prenatal exposure to a mixture of these EDCs, dams were orally administered either saline (control), BPA (5μg/Kg BW/day), high dose DEHP (HD-D; 7.5 mg/Kg BW/day), or a combination of BPA with HD-D in experiment 1; saline, BPA (5μg/Kg BW/day), low-dose DEHP (LD-D; 5μg/Kg BW/day) or a combination of BPA with LD-D in experiment 2. Gestational weights, number of abortions, litter size and weights, number of live births and stillbirths were recorded. Morphometric measures were obtained at birth and body weight, food and water intake were monitored weekly from postnatal weeks 3-12. Offspring were sacrificed at 16-24 weeks of age and organ weights were measured. The abortion rate of dams exposed to HD-D and the mixtures, BPA+LD-D and BPA+HD-D were higher at 9, 14 and 27% respectively. Prenatal exposure to BPA or HD-D significantly decreased relative thymus weights in male but not female offspring. Apoptotic cells were detected in thymus sections of both male and female offspring prenatally exposed to DEHP. Relative heart weights increased in BPA+HD-D exposed male offspring compared to the other groups. The results indicate that a mixture of BPA and DEHP, produced a pronounced effect on pregnancy outcomes. Male offspring appear to be more susceptible to the programming effects of these EDCs or their mixture suggesting a need to reconsider the possible additive, antagonistic or synergistic effects of EDC mixtures.



中文翻译:

双酚A和邻苯二甲酸二乙基己酯对Sprague-Dawley大鼠妊娠结局和后代发育的独立和联合作用

研究双酚A(BPA)和邻苯二甲酸二乙基己酯(DEHP)是内分泌干扰化学物质(EDC),但是研究表明,这些EDC混合物的作用并不明显。为了评估产前暴露于这些EDC混合物的后果,对母鼠口服盐水(对照),BPA(5μg/ Kg BW /天),高剂量DEHP(HD-D; 7.5 mg / Kg BW /天) ,或实验1中BPA与HD-D的组合;盐水,BPA(5μg/ Kg BW /天),低剂量DEHP(LD-D;5μg/ Kg BW /天)或实验2中BPA与LD-D的组合。妊娠体重,流产次数,产仔数并记录体重,活产和死产的数量。在出生时进行形态测量,并在产后3-12周每周监测体重,食物和水的摄入量。在16-24周龄处死后代并测量器官重量。暴露于HD-D和混合物BPA + LD-D和BPA + HD-D的大坝的流产率分别较高,分别为9%,14%和27%。产前暴露于BPA或HD-D可使雄性后代的相对胸腺重量显着降低,而雌性后代则没有。在产前暴露于DEHP的雄性和雌性后代的胸腺切片中均检测到凋亡细胞。与其他组相比,暴露于BPA + HD-D的雄性后代的相对心脏重量增加。结果表明,BPA和DEHP的混合物对妊娠结局产生了明显的影响。雄性后代似乎更容易受到这些EDC或其混合物的编程作用的影响,这表明需要重新考虑EDC混合物可能产生的累加,拮抗或协同作用。BPA + LD-D和BPA + HD-D分别较高,分别为9%,14%和27%。产前暴露于BPA或HD-D可使男性后代的相对胸腺重量显着降低,而女性后代则没有。在产前暴露于DEHP的雄性和雌性后代的胸腺切片中均检测到凋亡细胞。与其他组相比,暴露于BPA + HD-D的雄性后代的相对心脏重量增加。结果表明,BPA和DEHP的混合物对妊娠结局产生了明显的影响。雄性后代似乎更容易受到这些EDC或其混合物的编程作用的影响,这表明需要重新考虑EDC混合物可能产生的累加,拮抗或协同作用。BPA + LD-D和BPA + HD-D分别较高,分别为9%,14%和27%。产前暴露于BPA或HD-D可使男性后代的相对胸腺重量显着降低,而女性后代则没有。在产前暴露于DEHP的雄性和雌性后代的胸腺切片中均检测到凋亡细胞。与其他组相比,暴露于BPA + HD-D的雄性后代的相对心脏重量增加。结果表明,BPA和DEHP的混合物对妊娠结局产生了明显的影响。雄性后代似乎更容易受到这些EDC或其混合物的编程作用的影响,这表明需要重新考虑EDC混合物可能产生的累加,拮抗或协同作用。在产前暴露于DEHP的雄性和雌性后代的胸腺切片中均检测到凋亡细胞。与其他组相比,暴露于BPA + HD-D的雄性后代的相对心脏重量增加。结果表明,BPA和DEHP的混合物对妊娠结局产生了明显的影响。雄性后代似乎更容易受到这些EDC或其混合物的编程作用的影响,这表明需要重新考虑EDC混合物可能产生的累加,拮抗或协同作用。在产前暴露于DEHP的雄性和雌性后代的胸腺切片中均检测到凋亡细胞。与其他组相比,暴露于BPA + HD-D的雄性后代的相对心脏重量增加。结果表明,BPA和DEHP的混合物对妊娠结局产生了明显的影响。雄性后代似乎更容易受到这些EDC或其混合物的编程作用的影响,这表明需要重新考虑EDC混合物可能产生的累加,拮抗或协同作用。

更新日期:2020-09-15
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