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, VIRGINIA; VARAYOUD, JORGELINA; PACINI, GUILLERMINA; LUQUE, ENRIQUE HUGO; MILESI, MARÍA MERCEDES

Mar del Plata

Congreso; LXI ANNUAL MEETING ARGENTINE SOCIETY FOR CLINICAL INVESTIGATION (SAIC); 2016

Sociedad Argentina de Investigación Clínica (SAIC), la Sociedad Argentina de Inmunología (SAI) y la Sociedad Argentina de Farmacología Experimental (SAFE)

Usage of glyphosate-based herbicides (GBHs) has been expanded over the last decade. Recently, we found that oral exposure to a GBH in 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 (ER). It has been identified five promoters called E1, OT, O, ON, and OS which control ER transcription initiation yielding different transcripts with alternative 5´ untranslated regions. The purpose of this work was to investigate the effects of in utero and lactational exposure to a GBH over the control of ER 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 on GD5 (pre-implantation period), and uterine samples were collected and store at -80°C until analysis. Relative expression of total ER mRNA and ER 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, ER gene transcription was regulated by OS, O, OT and E1 promoters, regardless of treatment group. When we analyzed GBH effects, we detected an increase of total ER mRNA expression. Moreover, the increase in total ER mRNA in GBH group was mediated by an increased expression of ER-O variant. These findings showed that perinatal exposure to a GBH alters ER expression during the pre-implantation period, by affecting the relative abundance of alternative 5?-untranslated region of ER transcripts in the uterus. These alterations could explain, at least in part, the GBH-mediated subfertility.