Maternal exposure to mixtures of dienestrol, linuron and flutamide. Part I: Feminization effects on male rat offspring

• Published in: Food and chemical toxicology Vol. 139; p. 111256
• Main Authors: Schreiber, Elga, Garcia, Tània, González, Neus, Esplugas, Roser, Sharma, Raju Prasad, Torrente, Margarita, Kumar, Vikas, Bovee, Toine, Katsanou, Efrosini S., Machera, Kyriaki, Domingo, José Luis, Gómez, Mercedes
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2020
• Subjects: Animals; Animals, Newborn; Cryptorchidism - chemically induced; Cryptorchidism - physiopathology; Dienestrol; Dienestrol - toxicity; Dose-Response Relationship, Drug; Endpoint Determination; Female; Feminization - chemically induced; Feminization - physiopathology; Feminization effects; Flutamide; Flutamide - toxicity; Linuron; Linuron - toxicity; Male; Male rats; Maternal Exposure - adverse effects; Mixtures; Nipples - abnormalities; Nipples - drug effects; Organ Size - drug effects; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Prenatal Exposure Delayed Effects - physiopathology; Rats; Rats, Sprague-Dawley; Testis - abnormalities; Testis - drug effects; Flutamide; Dienestrol; Feminization effects; Male rats; Mixtures; Linuron
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2020.111256

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. [Display omitted] •Flutamide caused feminization to male pups.•At PND0/1, male and female pups cannot be well distinguished in FLU-treated groups.•Linuron decreased the viability of pups at the highest dose.•Feminizing effects due to maternal exposure through DIES and LIN were not observed.•Combinations of FLU + LIN and FLU + DIES increased NR, and decreased AGD.