Perinatal exposure to a glyphosate-based herbicide impairs female reproductive outcomes and induces second-generation adverse effects in Wistar rats

Abstract

Glyphosate-based herbicides (GBHs) are the most globally used herbicides raising the risk of environmental exposition. Here, we investigated whether perinatal exposure to low doses of a GBH alters the female reproductive performance, and/or induced second-generation effects related to congenital anomalies or growth alterations. Pregnant rats (F0) received a GBH through food, in a dose of 2 mg (GBH-LD: GBH-low dose group) or 200 mg (GBH-HD: GBH-high dose group) of glyphosate/kg bw/day from gestational day (GD) 9 until weaning. Body weight gain and vaginal canal-opening of F1 females were recorded. Sexually mature F1 females were mated to evaluate their reproductive performance by assessing the pregnancy rate, and on GD19, the number of corpora lutea, the implantation sites (IS) and resorption sites. To analyze second-generation effects on F2 offspring, we analyzed the fetal morphology on GD19, and assessed the fetal length and weight, and the placental weight. GBH exposure neither altered the body weight gain of F1 females, nor vaginal opening onset. Although all GBH-exposed F1 rats became pregnant, a lower number of IS was detected. F2 offspring from both GBH groups showed delayed growth, evidenced by lower fetal weight and length, associated with a higher incidence of small for gestational age fetuses. In addition, higher placental weight and placental index were found in F2 offspring from GBH-HD dams. Surprisingly, structural congenital anomalies (conjoined fetuses and abnormally developed limbs) were detected in the F2 offspring from GBH-HD group. In conclusion, perinatal exposure to low doses of a GBH impaired female reproductive performance and induced fetal growth retardation and structural congenital anomalies in F2 offspring.

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Acknowledgements

We thank Juan Grant and Juan C. Villarreal for technical assistance and animal care. We are grateful to Department of Mathematics and Laboratorio de Investigación y Servicios en Bioestadística (LISEB), in particular to Professor Stella Vaira, from Facultad de Bioquímica y Ciencias Biológicas (UNL) for the help with the statistical analyses. This work was supported by grants from the UNL (CAI+D 2016 PIC 50420150100085LI), the Argentine National Agency of Scientific and Technological Promotion (ANPCyT; PICT 2014 N° 2125, PICT 2014 N° 1522, PICT 2014 N° 1628) and CONICET. MMM, JV, and EHL are Career Investigators of the CONICET. VL is a fellow of Bunge and Born Foundation (Argentina); GP is an undergraduate student of Facultad de Bioquímica y Ciencias Biológicas (UNL); MRR is Professor of Facultad de Ingeniería Química (UNL); LDD is a fellow of the CONICET.

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Correspondence to María M. Milesi.

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Milesi, M.M., Lorenz, V., Pacini, G. et al. Perinatal exposure to a glyphosate-based herbicide impairs female reproductive outcomes and induces second-generation adverse effects in Wistar rats. Arch Toxicol 92, 2629–2643 (2018). https://doi.org/10.1007/s00204-018-2236-6

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Keywords

  • Glyphosate-based herbicide
  • Uterus
  • Reproductive performance
  • Feto-placental parameters