Analysis of the uterine lumen in fertility-classified heifers: II. Proteins and metabolites

Authors: MORAES, JOAO - University Of Missouri; BEHURA, SUSANTA - University Of Missouri; BISHOP, JEANETTE - Colorado State University; HANSEN, THOMAS - Colorado State University; Geary, Thomas; SPENCER, THOMAS - University Of Missouri

Submitted to: Biology of Reproduction
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/1/2019
Publication Date: 10/16/2019
Citation: Moraes, J.G., Behura, S.K., Bishop, J.V., Hansen, T.R., Geary, T.W., Spencer, T.E. 2019. Analysis of the uterine lumen in fertility-classified heifers: II. Proteins and metabolites. Biology of Reproduction. 102(3):571-587. https://doi.org/10.1093/biolre/ioz197.
DOI: https://doi.org/10.1093/biolre/ioz197

Interpretive Summary: Exact signaling between the uterus and embryo is needed for embryo growth and survival in all mammals. An embryo needs specific nutrients from the uterus to grow and attach to the uterus. Repeated embryo transfer was used to classify cows as high fertile (HF), sub-fertile (SF) and infertile (IF). Specific nutrients and gene expression signals (mRNA) in the uterus of day 17 pregnant and non-pregnant cows were studied. The signal for embryo presence (IFNT) was greater in pregnant cows and greater in pregnant HF than SF cows. However, IFNT mRNA levels were not different between HF and SF cows. Several of the nutrients needed for embryo growth and development were greater in the uterus of pregnant HF than SF cows. A similar increase in genes related to these nutrients were also increased in pregnant HF cows. This study supports the idea that uterine nutrients differ between highly fertile and sub-fertile cows and these differences affect embryo growth and survival.

Technical Abstract: Survival and growth of the bovine conceptus (embryo and associated extraembryonic membranes) is dependent on endometrial secretions or histotroph found in the uterine lumen. Previously, serial embryo transfer was used to classify heifers as high fertile (HF), subfertile (SF), or infertile (IF). Here, we investigated specific histotroph components (proteins and metabolites) in the uterine lumen of day 17 pregnant and nonpregnant fertility-classified heifers. IFNT concentrations in uterine luminal flush (ULF) were higher in pregnant heifers classified as high fertile (HF) than in subfertile (SF) animals. Although there were no differences in IFNT mRNA levels between HF and SF conceptuses, the increased IFNT abundance in ULF from HF heifers were due to conceptus size. Further, no differences in endometrium expression of selected classical and nonclassical interferon-stimulated genes (ISGs) were observed, suggesting that IFNT signaling in the endometrium of pregnant HF and SF heifers was similar and not a major cause of reduced uterine receptivity in SF animals. Pregnancy induced significant changes in the ULF proteins with several increased by pregnancy and greater in pregnant HF than SF heifers including those involved in energy metabolism (ACAA2, ENO1, TKT, PGD), oxidative stress (GSS), amino acid metabolism (PSPH, GOT1, LAP3, WARS, AHCY), and cell proliferation and differentiation (RAC1, HSPB1, CDC42). Metabolomics analysis found that pregnancy induced 271 differential metabolites in the ULF of HF heifers, but no differences were identified in ULF of SF heifers that were pregnant or open. The majority of the metabolites that increased in the ULF of pregnant HF as compared to SF heifers were associated with energy and amino acid metabolism. Hence, the observed differences in ULF proteome and metabolome are hypothesized to influence uterine receptivity and consequently conceptus development and survival.