Exacerbated conceptus signaling does not favor establishment of pregnancy in beef cattle

T Martins,M Binelli,C C Rocha,B O Cardoso,A C Basso,A M Gonella-Diaza,E O S Batista,O A Ojeda-Rojas,M Sponchiado

doi:10.1186/s40104-018-0302-9

Abstract

BackgroundInsufficient production of anti-luteolytic signals by the pre-attachment embryo is considered a major cause of pregnancy failure in cattle. We tested the hypothesis that transfer of multiple blastocysts (n = 5/recipient) and progesterone (P4) supplementation amplify anti-luteolytic signaling and reduce embryonic losses in beef cattle. Cows detected in estrus (D0; n = 104) were assigned randomly to receive 150 mg of injectable long-acting P4 (iP4) or vehicle (non-iP4) on D4 and transcervical transfer of none or five, grade 1, not-frozen, in vitro-produced blastocysts, on D7. Luteal development and time of structural luteolysis were monitored by ultrasonography. Plasma P4 concentrations were determined on D4, D5 and D7, and daily between D14 and D20. Conceptus signaling was monitored by transcript abundance of interferon-stimulated gene 15 (ISG15) in peripheral blood mononuclear cells isolated on D14, D16, D18 and D20. Early embryonic mortality (EEM) was defined as the absence of ISG15 mRNA upregulation over time and/or luteal regression up to D20. Late embryonic mortality (LEM) was defined as the absence of a conceptus with a heartbeat on pregnancy diagnosis at D30 (PD30) after observing upregulation of ISG15 mRNA and extension of luteal lifespan. Pregnant cows presented conceptuses with heartbeat at PD30.ResultsOn D5, iP4-treated cows had P4 concentrations 2.07-fold greater than non-iP4 treated (P < 0.001). On D7, P4 concentrations were similar. Pregnant and LEM animals showed a progressive increase in the abundance of ISG15 from D14 to D20. iP4-treated cows detected pregnant at PD30 had 1.53-fold greater abundance of ISG15 mRNA between D14 and D20 than non-iP4 treated cows (P = 0.05). iP4 doubled the frequency of EEM while it did not affect LEM. At PD30, embryonic survival was 37.0% vs. 55.6% for iP4-treated vs. control cows. Majority of pregnant cows (71%) presented only a single viable embryo.ConclusionsA substantial proportion of cows had EEM (31%) and LEM (20%) even after transferring multiple blastocysts. This argues that mortality was due to poor uterine receptivity that could not be reversed by supplemental P4 or overcome by transferring multiple blastocysts. Further, a given uterine environment was not necessarily adequate to all embryos.

Highlights

Insufficient production of anti-luteolytic signals by the pre-attachment embryo is considered a major cause of pregnancy failure in cattle
Increased concentrations of P4 stimulate endometrial secretions [9], accelerate conceptus elongation and subsequent release of IFNT into the uterine lumen [10,11,12] in cattle. Despite of such clear positive effect on pregnancy establishment, the reported fertility outcome to early diestrus P4 supplementation is variable [13, 14]
Effect of P4 supplementation and embryo transfer on ovarian and endocrine variables Concentrations of P4 in plasma between D4 and D7 were affected by a day by injectable long-acting P4 (iP4) treatment interaction

Summary

Introduction

Insufficient production of anti-luteolytic signals by the pre-attachment embryo is considered a major cause of pregnancy failure in cattle. During the first three weeks post-insemination, embryonic mortality accounts for up to two-thirds of overall pregnancy losses in cattle [1,2,3], constituting a major cause of pregnancy failures Explanation for this massive loss is related to a functional incompetence of the uterus to support embryonic development, embryonic incompetence or both [4]. Increased concentrations of P4 stimulate endometrial secretions [9], accelerate conceptus elongation and subsequent release of IFNT into the uterine lumen [10,11,12] in cattle. Despite of such clear positive effect on pregnancy establishment, the reported fertility outcome to early diestrus P4 supplementation is variable [13, 14]. An asynchrony between stimuli provided by the uterine environment and required by the developing embryo [18] can be an explanation for the variable fertility results

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