Food and Chemical Toxicology ( IF 4.3 ) Pub Date : 2020-07-05 , DOI: 10.1016/j.fct.2020.111560 Virginia Lorenz 1 , Guillermina Pacini 1 , Enrique H Luque 2 , Jorgelina Varayoud 2 , María M Milesi 2
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.
中文翻译:
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围产期暴露于草甘膦或基于草甘膦的制剂会在大鼠的接受状态期间破坏激素和子宫环境。
我们调查了围产期暴露于草甘膦基除草剂(GBH)或单独使用草甘膦(Gly)的围产期对女性生育率以及荷尔蒙和子宫环境的影响。F0妊娠大鼠从妊娠第9天(GD)到断奶,口服草甘膦(GBH)或Gly,剂量为2 mg草甘膦/ kg /天。对F1雌性进行评估以确定GD19的生殖性能。GD5(着床前期)的性激素水平,雌激素受体α(ERα),孕激素受体(PR)的表达以及着床相关基因。GBH和Gly诱导F1大鼠植入前损失。GBH和Gly组表现出较高的17β-雌二醇血清水平,而孕酮没有变化。两种化合物均增加了子宫ERα蛋白的表达,在转录水平上无差异。而只有Gly降低PR mRNA表达。此外,GBH和Gly下调Hoxa10和Lif基因,Muc1和Areg表达没有差异。总而言之,围产期暴露于GBH或Gly会破坏受体状态下的关键激素和子宫分子靶标,可能与植入失败有关。总体而言,在暴露于GBH和Gly的大鼠中发现了相似的结果,表明活性成分可能是造成有害作用的主要原因。