Supplementing with progesterone (P4) at the beginning of diestrus increases pregnancy rates, but also anticipates the functional and structural regression of the corpus luteum (CL) which may impair the success of the strategy. We speculate that this anticipation (early luteolysis) can be prevented by the presence of the conceptus (embryo + attached membranes), which is the main agent responsible for maintaining the CL. However, this effect is not yet known and the present study aims to investigate it. For this, experiments have been proposed to test the following hypotheses: (experiment 1) inseminated cows supplemented with P4 have a lower frequency of premature luteolysis than cows not inseminated and supplemented with P4; (Experiment 2) in cows treated with P4 the presence of embryo increases the likelihood of conception, therefore, anticipated luteolytic process occurs to a lesser extent than cows treated with P4 without embryo; (Experiment 3) in cows supplemented with P4 the presence of the embryo decrease the expression of receptors that control the release of PGF2a and displaces PGF2a synthesis to PGE2 in the endometrium. In experiment 1, multiparous non-lactating Nelore cows detected in heat will be selected to receive three treatments: AI and 150 mg of long-acting P4 (P4-LA) on Day 3 (Day 0: ovulation); diluent at the time of AI and 150 mg of LA-P4 on Day 3 (positive control) or diluent at the time of AI and placebo on Day 3 (negative control). In experiment 2, the animals will be selected on Day 3 to receive P4-LA or placebo and transfer of 0, 1 or 5 embryos (ET) on Day 7 (2 by 3 factorial arrangement). The luteal function in the experiments 1 and 2 will be monitored daily by ultrasound and Doppler examination and by dosage of P4 plasma concentrations on Days 3, 9, 11, 13, 15, 17, 19 and 21. In experiment 3, the cows will be selected on Day 3 to receive P4-LA or placebo and transfer of 0 or 5 embryos on Day 7 (2x2 factorial). Endometrial tissue fragments post-mortem will be collected on the day preceding the moment of greatest occurrence of premature luteolysis previously established in the experiment 2. It will be analysed the abundance of transcripts linked to control of luteolysis time [progesterone receptor (PGR), estrogen receptor 1 (ESR1), estrogen receptor 2 (ESR2), oxytocin receptor (OXTR)], synthesis of prostaglandins (PGs) [phospholipase A2, group X (PLA2G10), prostaglandin-endoperoxidase synthase 2 (PTGS2)], synthesis of PGF2a [aldo-keto reductase family 1, member B1 (AKR1B1), aldo-keto reductase family 1, member C3 (AKR1C3), aldo-keto reductase family 1, C4 member (AKR1C4), carbonyl reductase 1 (CBR1))] and synthesis of PGE2 [ie prostaglandin E synthase (PGES), prostaglandin E synthase 2 (PTGES2) and prostaglandin E synthase 3 (PTGES3)]. In cows challenged with P4 it is expected that the incidence of premature luteolysis is attenuated by AI and TE or even annulled by transfer of 5 embryos. In the endometrium of cows stimulated by P4 the presence of the conceptus can decrease the expression of ESR1 genes, ESR2 and OXTR, not change the PLA2G10 and PTGS2 (remain increased) and increase the expression of PGE synthase ( PGES, PGES2 and PGES3 ) over the genes involved in the synthesis of PGF2a (ie AKR1B1, AKR1C3, AKR1C4 and CBR1). Results of this study, will give greater support for the efficient and safe use of supplementation with long-acting injectable P4.
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