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Maternal exposure to mixtures of dienestrol, linuron and flutamide. Part I: Feminization effects on male rat offspring.
Food and Chemical Toxicology ( IF 4.3 ) Pub Date : 2020-03-12 , DOI: 10.1016/j.fct.2020.111256
Elga Schreiber 1 , Tània Garcia 1 , Neus González 1 , Roser Esplugas 1 , Raju Prasad Sharma 2 , Margarita Torrente 3 , Vikas Kumar 4 , Toine Bovee 5 , Efrosini S Katsanou 6 , Kyriaki Machera 6 , José Luis Domingo 1 , Mercedes Gómez 1
Affiliation  

Exposure to endocrine-disrupting compounds (EDCs) during pregnancy can result in negative health effects in later generations, including sex changes and feminization. The present study assessed the feminization effects on male offspring rats of three EDCs: Dienestrol (DIES), Linuron (LIN), and Flutamide (FLU). Sexually mature female rats were exposed from gestation day (GD) 6 until postnatal day (PND) 21 to: 0.37, 0.75, 1.5, 3.12 or 6.25 μg/kg/day of DIES, 1.5, 3, 6, 12.5, 25 or 50 mg/kg/day of LIN, 3.5, 6.7, 12.5, 25 or 50 mg/kg/day of FLU, and the following mixtures: FLU + DIES (mg/kg/day+μg/kg/day), 3.5 + 0.37, or 3.5 + 3, 25 + 0.37, or 25 + 3; FLU + LIN (mg/kg/day + mg/kg/day), 3.5 + 12.5, or 25 + 12.5; and DIES + LIN (μg/kg/day + mg/kg/day), 0.37 + 12.5, or 3 + 12.5. Anogenital distance (AGD), nipple retention (NR) and cryptorchidism were evaluated. FLU produced a decrease of AGD, an increase of NR, and an increase of cryptorchidism at the highest dose. None of these three endpoints were significantly affected by LIN or DIES treatments alone. Combinations of FLU + LIN and FLU + DIES increased NR, and decreased AGD, while DIES + LIN did not produce any effects in male pups. Results show that FLU is able to induce feminization in male pups, while binary combinations of LIN and DIES did not modify the effects produced by FLU.

中文翻译:

孕产妇接触地烯雌酚,利奴隆和氟他胺的混合物。第一部分:女性化对雄性大鼠后代的影响。

怀孕期间接触破坏内分泌的化合物(EDC)可能对后代造成负面健康影响,包括性别变化和女性化。本研究评估了三种EDC对雌性后代大鼠的女性化作用:地烯雌酚(DIES),利奴隆(LIN)和氟他胺(FLU)。性成熟雌性大鼠从妊娠第6天(GD)到出生后第21天(PND)暴露于0.37、0.75、1.5、3.12或6.25μg/ kg /天的DIES,1.5、3、6、12.5、25或50 LIN的mg / kg /天,FLU的3.5、6.7、12.5、25或50 mg / kg /天以及以下混合物:FLU + DIES(mg / kg /天+μg/ kg /天),3.5 + 0.37 ,或3.5 + 3、25 + 0.37或25 + 3;FLU + LIN(mg / kg /天+ mg / kg /天),3.5 + 12.5或25 + 12.5;和DIES + LIN(μg/ kg /天+ mg / kg /天),0.37 + 12.5或3 + 12.5。肛门生殖器距离(AGD),评估了乳头retention留(NR)和隐睾症。在最高剂量下,FLU导致AGD降低,NR升高和隐睾增加。仅使用LIN或DIES治疗,这三个终点均未受到显着影响。FLU + LIN和FLU + DIES的组合增加了NR,降低了AGD,而DIES + LIN对雄性幼崽没有任何作用。结果表明,FLU能够诱导雄性幼犬女性化,而LIN和DIES的二元组合并未改变FLU产生的作用。DIES + LIN对雄性幼崽没有任何影响。结果表明,FLU能够诱导雄性幼犬女性化,而LIN和DIES的二元组合并未改变FLU产生的作用。DIES + LIN对雄性幼崽没有任何影响。结果表明,FLU能够诱导雄性幼犬女性化,而LIN和DIES的二元组合并未改变FLU产生的作用。
更新日期:2020-03-12
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