Induced endometrial inflammation compromises conceptus development in dairy cattle†

Abstract

Endometrial inflammation is associated with reduced pregnancy per artificial insemination (AI) and increased pregnancy loss in cows. It was hypothesized that induced endometritis alters histotroph composition and induces inflammatory signatures on conceptus that compromise development. In Experiment 1, lactating cows were assigned to control (CON; n = 23) or to an intrauterine infusion of Escherichia coli and Trueperella pyogenes (ENDO; n = 34) to induce endometritis. Cows received AI 26 days after treatment, and the uterine fluid and conceptuses were collected on day 16 after AI. In Experiment 2, Holstein heifers were assigned to CON (n = 14) or ENDO (n = 14). An embryo was transferred on day 7 of the estrous cycle, and uterine fluid and conceptuses were recovered on day 16. Composition of histotroph and trophoblast and embryonic disc gene expression were assessed. Bacterial-induced endometritis in lactating cows altered histotroph composition and pathways linked to phospholipid synthesis, cellular energy production, and the Warburg effect. Also, ENDO reduced conceptus length in cows and altered expression of genes involved in pathogen recognition, nutrient uptake, cell growth, choline metabolism, and conceptus signaling needed for maternal recognition of pregnancy. The impact of ENDO was lesser on conceptuses from heifers receiving embryo transfer; however, the affected genes and associated pathways involved restricted growth and increased immune response similar to the observed responses to ENDO in conceptuses from lactating cows. Bacterial-induced endometrial inflammation altered histotroph composition, reduced conceptus growth, and caused embryonic cells to activate survival rather than anabolic pathways that could compromise development.

Keywords: conceptus development; dairy cow; histotroph metabolome; induced endometritis; mRNA expression.

Graphical Abstract

Figure 1

Effect of treatment on the mRNA expression of conceptus tissues from lactating dairy cows receiving AI (A) or heifers receiving ET (B). Conceptuses were recovered on day 16 of pregnancy and dissected into trophoblast and embryonic disc. Heat maps were generated including differently expressed genes (P ≤ 0.10) affected by treatment for the experiment with lactating cows receiving AI or for the experiment with heifers receiving ET. Genes were separated using the average linkage clustering method and following Euclidean distance measurement approach. The mRNA expression increases from red to green, and data based on genes were compared across the rows and presented on a Z-score-based scaling system.

Figure 2

Effect of treatment on the histotroph metabolome from lactating dairy cows on day 16 of pregnancy presented as: volcano plot (A); principal component analysis (B); partial least squares—discriminate analysis (C); 15 affected metabolites by treatment based on the VIP score (D); and heatmap of the 50 metabolites discriminating ENDO from CON treatment based on the VIP score (E). The histotroph was collected using the cytobrush technique on day 16 of pregnancy from 8 CON and 12 ENDO cows.

Figure 3

Summary plots for quantitative enrichment analysis based on small-molecule pathway databases (A) and the KEGG pathway (B). The histotroph was collected using the cytobrush technique on day 16 of pregnancy from 8 CON and 12 ENDO cows.