Ingaramo Paola I, Varayoud Jorgelina, Milesi María M, Schimpf Marlise Guerrero, Muñoz-de-Toro Mónica, Luque Enrique H
Instituto de Salud y Ambiente del Litoral (ISAL)Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Santa Fe, Argentina.
Instituto de Salud y Ambiente del Litoral (ISAL)Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Santa Fe, Argentina
Reproduction. 2016 Nov;152(5):403-15. doi: 10.1530/REP-16-0171. Epub 2016 Aug 2.
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.
在本研究中,我们调查了新生大鼠暴露于草甘膦基除草剂(GBH)是否会改变成年大鼠的生殖性能以及蜕膜化过程中涉及的分子机制。新生雌性大鼠在出生后第1、3、5和7天接受赋形剂或2mg/kg/天的GBH。在出生后第90天,将大鼠进行交配,以评估(i)妊娠第19天的生殖性能,以及(ii)妊娠第9天着床部位(IS)的卵巢类固醇水平、子宫形态、子宫内膜细胞增殖、凋亡和细胞周期调节因子,以及调节子宫蜕膜化的内分泌途径(类固醇受体/COUP-TFII/Bmp2/Hoxa10)。GBH暴露组在妊娠第19天的吸收部位数量显著增加,这与蜕膜化反应改变有关。事实上,在妊娠第9天,GBH处理的大鼠在着床部位出现形态学变化,同时雌激素和孕激素受体表达降低,COUP-TFII(Nr2f2)和Bmp2 mRNA下调,HOXA10和增殖标志物Ki67(Mki67)在着床部位的表达增加。我们得出结论,子宫内膜蜕膜化改变可能是GBH诱导植入后胚胎丢失的机制。