Perinatal exposure to glyphosate or a glyphosate-based formulation disrupts hormonal and uterine milieu during the receptive state in rats

• Published in: Food and chemical toxicology 2020-09, Vol.143, p.111560, Article 111560
• Main Authors: Lorenz, Virginia, Pacini, Guillermina, Luque, Enrique H., Varayoud, Jorgelina, Milesi, María M.
• Format: Article
• Language: English
• Subjects: 17β-estradiol; Animals; Animals, Newborn; Embryo Implantation - drug effects; Estrogen receptor alpha; Estrus; Female; Gene Expression Regulation - drug effects; Glycine - analogs & derivatives; Glycine - toxicity; Glyphosate; Herbicides - toxicity; Hormones - metabolism; Implantation; Implantation-related genes; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Reproduction - drug effects; Uterus
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2020.111560

We investigated the effects of perinatal exposure to a glyphosate-based herbicide (GBH) or glyphosate alone (Gly) on female fertility and the hormonal and uterine milieu during the preimplantation period. F0 pregnant rats orally received a GBH or Gly in a dose of 2 mg of glyphosate/kg/day from gestational day (GD) 9 until weaning. F1 females were evaluated to determine the reproductive performance on GD19; and the sex steroid serum levels, the expression of estrogen receptor alpha (ERα), progesterone receptor (PR) and implantation-related genes on GD5 (preimplantation period). GBH and Gly induced preimplantation losses in F1 rats. GBH and Gly groups exhibited higher 17β-estradiol serum levels, without changes in progesterone. Both compounds increased the uterine ERα protein expression, with no differences at transcript level; and only Gly decreased PR mRNA expression. Also, GBH and Gly downregulated Hoxa10 and Lif genes, with no difference in Muc1 and Areg expression. To conclude, perinatal exposure to a GBH or Gly disrupted critical hormonal and uterine molecular targets during the receptive state, possibly associated with the implantation failures. Overall, similar results were found in GBH- and Gly-exposed rats, suggesting that the active principle might be the main responsible for the deleterious effects. •Glyphosate pure and in formulation increased preimplantation losses in F1 rats.•Glyphosate pure and in formulation increased serum 17β-estradiol in early pregnancy.•Glyphosate pure and in formulation disrupted uterine implantation-related genes.•Glyphosate pure and in formulation induced similar deleterious effects.