Perinatal exposure to a glyphosate-based herbicide impairs female reproductive outcomes and induces second-generation adverse effects in Wistar rats
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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.
KeywordsGlyphosate-based herbicide Uterus Reproductive performance Feto-placental parameters
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.
Compliance with ethical standards
The manuscript does not contain clinical studies or patient data.
All applicable international, national, and institutional guidelines for the care and use of the animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
Conflict of interest
The authors declare that they have no conflict of interest.
- Barron S, Thomson A (1983) Obstetrical epidemiology. Academic Press, LondonGoogle Scholar
- Bernal J, Bernal JL, Martin MT, Nozal MJ, Anadón A, Martínez-Larrañaga MR, Martínez MA (2010) Development and validation of a liquid chromatography–fluorescence–mass spectrometry method to measure glyphosate and aminomethylphosphonic acid in rat plasma. J Chromatogr B 878:3290–3296CrossRefGoogle Scholar
- Defarge N, Takács E, Lozano VL, Mesnage R, Spiroux de Vendômois J, Séralini GE, Székács A (2016) Co-formulants in glyphosate-based herbicides disrupt aromatase activity in human cells below toxic levels. Int J Environ Res Public Health 13:264. https://doi.org/10.3390/ijerph13030264 CrossRefPubMedCentralGoogle Scholar
- EPA (2017) Glyphosate. Dietary exposure analysis in support of registration review. https://www.regulations.gov/document?D=EPA-HQ-OPP-2009-0361-0071 Accessed 12 Apr 2018
- Fischer R, Byerlee D, Edmeades G (2014) Crop yields and global food security: will yield increase continue to feed the world? Australian Centre for International Agricultural Research, CanberraGoogle Scholar
- MacDonald MG, Seshia MM, Mullett MD (2005) Avery’s neonatology pathophysiology and management of the newborn. Lippincott Williams and Wilkins, PhiladelphiaGoogle Scholar
- Oulkar DP, Hingmire S, Goon A, Jadhav M, Ugare B, Thekkumpurath AS, Banerjee K (2017) Optimization and validation of a residue analysis method for glyphosate, glufosinate, and their metabolites in plant matrixes by liquid chromatography with tandem mass spectrometry. J Assoc Off Anal Chem Int 100:631–639Google Scholar
- SANTE (2015) Guidance document on analytical quality control and method validation procedures for pesticides residues analysis in food and feed. European commission, SANTE/11945/2015. http://www.eurl-pesticides.eu Accessed 22 Dec 2017
- Test Biotech (2013) High levels of residues from spraying with glyphosate found in soybeans in Argentina. http://www.testbiotech.org/en/node/926 Accessed 12 Apr 2018
- WHO (2017) Sexual and reproductive health: infertility is a global public health issue. http://www.who.int/reproductivehealth/topics/infertility/perspective/en/ Accessed 22 Dec 2017