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产前暴露于环境相关低剂量邻苯二甲酸二丁酯会降低CD-1小鼠的胎盘效率。

Prenatal Exposure to Environmentally Relevant Low Dosage Dibutyl Phthalate Reduces Placental Efficiency in CD-1 Mice.

作者信息

Pontifex Tasha, Yang Xinran, Tracy Ayna, Burns Kimberlie, Craig Zelieann, Zhou Chi

机构信息

School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, AZ, United States.

Department of Obstetrics and Gynecology, The University of Arizona, Tucson, AZ, United States.

出版信息

bioRxiv. 2024 May 2:2024.02.26.582170. doi: 10.1101/2024.02.26.582170.

Abstract

INTRODUCTION

Dibutyl phthalate (DBP), a phthalate congener, is widely utilized in consumer products and medication coatings. Women of reproductive age have a significant burden of DBP exposure through consumer products, occupational exposure, and medication. Prenatal DBP exposure is associated with adverse pregnancy/fetal outcomes and cardiovascular diseases in the offspring. However, the role of fetal sex and the general mechanisms underlying DBP exposure-associated adverse pregnancy outcomes are unclear. We that prenatal DBP exposure at an environmentally relevant low dosage adversely affects fetal-placental development and function during pregnancy in a fetal sex-specific manner.

METHODS

Adult female CD-1 mice (8-10wks) were orally treated with vehicle (control) or with environmentally relevant low DBP dosages at 0.1 μg/kg/day (refer as DBP0.1) daily from 30 days before pregnancy through gestational day (GD) 18.5. Dam body mass composition was measured non-invasively using the echo-magnetic resonance imaging system. Lipid disposition in fetal labyrinth and maternal decidual area of placentas was examined using Oil Red O staining.

RESULTS

DBP0.1 exposure did not significantly affect the body weight and adiposity of non-pregnant adult female mice nor the maternal weight gain pattern and adiposity during pregnancy in adult female mice. DBP0.1 exposure does not affect fetal weight but significantly increased the placental weight at GD18.5 (indicative of decreased placental efficiency) in a fetal sex-specific manner. We further observed that DBP0.1 significantly decreased lipid disposition in fetal labyrinth of female, but not male placentas, while it did not affect lipid disposition in maternal decidual.

CONCLUSIONS

Prenatal exposure to environmentally relevant low-dosage DBP adversely impacts the fetal-placental efficiency and lipid disposition in a fetal sex-specific manner.

摘要

引言

邻苯二甲酸二丁酯(DBP)是一种邻苯二甲酸酯同系物,广泛应用于消费品和药物涂层中。育龄女性通过消费品、职业接触和药物接触DBP的负担较重。产前接触DBP与后代不良妊娠/胎儿结局及心血管疾病有关。然而,胎儿性别在其中的作用以及DBP暴露相关不良妊娠结局的一般机制尚不清楚。我们发现,孕期暴露于环境相关低剂量的DBP会以胎儿性别特异性方式对胎儿 - 胎盘发育及功能产生不利影响。

方法

成年雌性CD - 1小鼠(8 - 10周龄)在怀孕前30天至妊娠第18.5天,每天口服给予赋形剂(对照)或环境相关低剂量的DBP,剂量为0.1μg/kg/天(称为DBP0.1)。使用回声磁共振成像系统无创测量母鼠身体成分。采用油红O染色检查胎盘胎儿迷路和母体蜕膜区的脂质分布。

结果

DBP0.1暴露对未怀孕成年雌性小鼠的体重和肥胖无显著影响,对成年雌性小鼠孕期的体重增加模式和肥胖也无显著影响。DBP0.1暴露不影响胎儿体重,但在妊娠第18.5天以胎儿性别特异性方式显著增加胎盘重量(表明胎盘效率降低)。我们进一步观察到,DBP0.1显著降低雌性胎盘胎儿迷路中的脂质分布,但对雄性胎盘无此影响,同时它不影响母体蜕膜中的脂质分布。

结论

产前暴露于环境相关低剂量的DBP会以胎儿性别特异性方式对胎儿 - 胎盘效率和脂质分布产生不利影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82df/11067625/ccb0bf85f54c/nihpp-2024.02.26.582170v2-f0001.jpg

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