Estradiol modulates the expression of genes involved in the synthesis of endometrial PGF2a in cows

In cattle, estradiol exerts an important role in endometrial PGF2α release, associated with luteolysis. The production of PGF2α results from the stimulation of oxytocin receptors and the subsequent activation of a cascade of intracellular events. . However, the molecular mechanisms by which estradiol acts in the endometrial PGF2a synthesis are little known.. The hypothesis is that estradiol stimulates gene expression of proteins involved in PGF2α synthesis in the bovine endometrium. Nelore (N = 52), pluriparous, cyclic and non-lactating cows received 2 mg of estradiol benzoate (Sincrodiol Gold fino® Cravinhos, Brazil) and an intravaginal progesterone device (1g; Sincrogest; Ourofino®, Cravinhos, Brazil) during 8 days. The cows received 0.5 mg of sodium cloprostenol (Sincrocio; Ourofino, Cravinhos, Brazil) via IM, 48 hours before the device removal and a second application at the removal. On day 15 of the estrous cycle (D0; estrus) the following treatments were administered: placebo (P; 5 ml of ethanol 50%; IV), estradiol (E; 5mL of 50% ethanol containing 3 mg of 17β estradiol; IV) or control (not treated). The time of treatments application was considered as time 0. Cows were subjected to a transcervical endometrial biopsy, and according to the time of biopsy were divided into the following groups: control group on time 0 (C; n = 10 ), time 4 hours (E4; P4 n = 11 and n = 10) or time 7 hours (E7, n = 10 and P7; n = 11). The tissue obtained by biopsy was analyzed by qRT-PCR for relative quantification of the genes : PTGS2, PLA2G4, ESR1, ESR2, OXTR, PKCα, PKCβ, AKR1CB1, and AKR1C4. The abundance of transcripts was analyzed by two-way ANOVA. The PTGS2 gene (P u003c 0.05) showed lower expression in P7 and E7 groups compared to P4 and E4 groups, respectively. Expression of PLA2G4 and ESR1 genes in the E4 group was lower compared to E7 (P u003c 0.05). There was lower expression of the gene ESR2 in E4 and E7 groups compared to the other groups (P u003c 0.05) and more OXTR transcripts in E4 and E7 groups (P u003c 0.05) compared to counterparts. There was a down regulation of PRKCα transcripts in the E7 group compared to other groups (P u003c 0.05). Also, a lower PRKCβ expression in P7 and E7 groups (P u003c 0.05) compared to the others. The expression AKR1B1 and AKR1C4 was lower (P u003c 0.05) in E4 and E7 groups compared to the other groups. It is concluded that, with the exception of OXTR, estradiol administration reduced gene expression of most of the proteins involved in PGF2a synthesis, indicating an acute negative feedback in the transcription of these genes. It is suggested that, at a time prior to the biopsies, there has been an increase in the expression of those genes. Thus, it becomes necessary to evaluate the protein expressioment.n, to determine if the decrease in the abundance of the transcripts is associated with an increase in the abundance of proteins after four hours of treat.