Perinatal exposure to a glyphosate based herbicide modifies the abundance of estrogen receptor alpha transcripts with alternative 5?-untranslated regions in the pre-implantation rat uterus

LORENZ V; VARAYOUD J; PACINI G; LUQUE EH; MILESI MM

Congreso; SAIC 2016; 2016

Usage of glyphosate-based herbicides (GBHs) has been expandedover the last decade. Recently, we found that oral exposure to a GBHin rats during perinatal period (pregnancy and lactation)produced subfertility as a consequence of implantation failures. Implantation is a complex process regulated by endocrine signaling pathways primary mediated via steroid receptors, such as estrogen receptor alpha (ERA).It has been identified five promoters called E1, OT, O, ON, and OSwhich control ER transcription initiation yielding different transcripts withalternative5´ untranslatedregions.The purpose of this work was to investigate the effects of in utero and lactational exposure to a GBHover the control of ERA expression in the pre-implantation uterus. Pregnant rats (F0) were orally exposed to 200 mg GBH/Kg/day through food from gestational day (GD) 9 until weaning (postnatal day 21, PND21). When F1 females reached the sexual maturity (PND90)were mated with males of proven fertility, and pregnancy was confirmed by vaginal smears. Pregnant F1 females were sacrificed onGD5 (pre-implantation period), and uterine samples were collected and store at -80°C until analysis.Relative expression of total ERA mRNA and ERA transcripts containing alternative 5?-untranslated regions E1, OT, O, ON, and OS was evaluated by real time RT-PCR. First we found that during the pre-implantation period, ERA gene transcription was regulated by OS, O, OT and E1 promoters, regardless of treatment group. When we analyzedGBH effects, we detected an increase of total ERA mRNA expression. Moreover, the increase in total ER mRNA in GBH groupwas mediated by an increased expression of ERA-Ovariant. These findings showed that perinatal exposure to a GBHalters ERA expression during the pre-implantation period, by affecting the relative abundance of alternative 5?-untranslated regionof ERA transcripts in the uterus. These alterations could explain, at least in part, the GBH-mediated subfertility.