Effects of neonatal exposure to a glyphosate-based herbicide on female rat reproduction

Abstract

In this study, we investigated whether neonatal exposure to a glyphosate-based herbicide (GBH) alters the reproductive performance and the molecular mechanisms involved in the decidualization process in adult rats. Newborn female rats received vehicle or 2 mg/kg/day of a GBH on postnatal days (PND) 1, 3, 5 and 7. On PND90, the rats were mated to evaluate (i) the reproductive performance on gestational day (GD) 19 and (ii) the ovarian steroid levels, uterine morphology, endometrial cell proliferation, apoptosis and cell cycle regulators, and endocrine pathways that regulate uterine decidualization (steroid receptors/COUP-TFII/Bmp2/Hoxa10) at the implantation sites (IS) on GD9. The GBH-exposed group showed a significant increase in the number of resorption sites on GD19, associated with an altered decidualization response. In fact, on GD9, the GBH-treated rats showed morphological changes at the IS, associated with a decreased expression of estrogen and progesterone receptors, a downregulation of COUP-TFII (Nr2f2) and Bmp2 mRNA and an increased expression of HOXA10 and the proliferation marker Ki67(Mki67) at the IS. We concluded that alterations in endometrial decidualization might be the mechanism of GBH-induced post-implantation embryo loss.

Reproductive disorders in female rats after prenatal exposure to betamethasone

“…The uterus, on the other hand, showed a significant difference between the areas of myometrium and endometrium in the treated group, which also showed an increase of post‐implantation loss and resorptions in the reproductive performance assessment, without alteration in fertility potential. It is possible that this result can be correlated with a lower endometrium tissue area, which might have compromised embryo implantation, placental and fetus development, leading to decreased fetus weight (Ingaramo et al ., ; Jauniaux et al ., ), as observed in the present work as well as an increase of myometric tissue area, promoting more tension inside the uterus and exacerbated contractility activity of this organ.…”

Re-registration Challenges of Glyphosate in the European Union

“…caused a testosterone-disruptor effect (Romano et al, 2012). In addition, nephrotoxicity (Hamdaoui et al, 2016), hepatotoxicity (ElShenawy, 2009;Haskovic et al, 2016;Tang et al, 2017;Lozano et al, 2018), neurotoxicity on dopaminergic markers (Hernández-Plata et al, 2015;Martínez et al, 2018), and on the immature rat hippocampus (Cattani et al, 2014), effects on intestine peristalsis (Chłopecka et al, 2014(Chłopecka et al, , 2017, sperm quality (Abarikwu et al, 2015;Dai et al, 2016) and reproductive toxicity (Owagboriaye et al, 2017), estrogenic effects (Vandenberg et al, 2012;Varayoud et al, 2017) and the effect of neonatal exposure to female adult reproductive performance (Ingaramo et al, 2016 have been demonstrated. Liver dysfunction observed in rats correlated with gut microbiome disturbances identified in a recent study : longterm effects of Roundup Grand Travaux Plus R at 3 doses (corresponding to glyphosate concentrations of 50 ng/l, 100 µg/l, and 2.25 g/l) on the gut microbiota in Sprague-Dawley rats were observed by determining 141 bacteria families by highthroughput sequencing, of which alteration of the Firmicutes to Bacteroidetes ratio was recorded at different levels in females (but not in males).…”

Effect of in ovo glyphosate injection on embryonic development, serum biochemistry, antioxidant status and histopathological changes in newly hatched chicks

“…Also, the Food and Drug Administration (FDA) determined the residue rate in animal products such as eggs (Food, 2017), referring to the potential risks of glyphosate. Also, many experiments for animal have evidenced that glyphosate can affect the embryo development (Ingaramo et al, 2016). Protection has not only impacted on adult fowls but also on the development of the embryo within the egg (Szabó, Szemerédy, Kormos, Lehel, & Budai, 2017).…”