A multi-omics analysis identifies molecular features associated with heifer fertility in a case-control design including Angus and Holstein cattle

Abstract

Background: Infertility or subfertility is a critical barrier to sustainable cattle production, including in heifers. The development of heifers that do not produce a calf within an optimum window of time is a critical factor for the profitability and sustainability of the cattle industry. The early identification of heifers with optimum fertility using molecular phenotyping is a promising approach to improving sustainability in beef and dairy cattle production. Results: Using a high-density single nucleotide polymorphism (SNP) chip, we collected genotypic data from 575,053 SNPs. We also produced quantitative transcriptome data for 12,445 genes (12,105 protein-coding genes, 228 long non-coding RNAs, and 112 pseudogenes) and proteome data for 213 proteins. We identified two SNPs significantly associated with heifer fertility (rs110918927, chr12: 85648422, P = 6.7x10-7; and rs109366560, chr11:37666527, P = 2.6x10-5). We identified two genes with differential transcript abundance (eFDR ≤ 0.002) between the two groups (Fertile and Sub-Fertile): Adipocyte Plasma Membrane Associated Protein (APMAP, 1.16 greater abundance in the Fertile group) and Dynein Axonemal Intermediate Chain 7 (DNAI7, 1.23 greater abundance in the Sub-Fertile group). Our analysis revealed that the protein Alpha-ketoglutarate-dependent dioxygenase FTO was more abundant in the plasma collected from Fertile heifers relative to their Sub-Fertile counterparts (FDR < 0.05). Interestingly, two proteins did not reach the significance threshold in the model accounting for all samples (Apolipoprotein C-II, APOC2 (FDRglmm = 0.06) and Lymphocyte cytosolic protein 1, LCP1 (FDRglmm = 0.06)), but both proteins were less abundant in the plasma of Fertile Holstein heifers (P < 0.05). Lastly, an integrative analysis of the three datasets identified a series of features (SNPs, gene transcripts, and proteins) that can be useful for the discrimination of heifers based on their fertility. When all features were utilized together, 21 out of 22 heifers were classified correctly based on their fertility category. Conclusions: Our multi-omics analyses confirm the complex nature of female fertility. Very importantly, our results also highlight differences in the molecular profile of heifers associated with fertility that transcend the constraints of breed-specific genetic background.

Sex-differences in proteasome-dependent K48-polyubiquitin signaling in the amygdala are developmentally regulated in rats

“…LC/MS data were analyzed in a similar manner to previously described methods [37]. Data were first log transformed (Log 2 (x + 1)) and proteins identified as having more than 15 zero values were excluded from analysis.…”

Anti‐Müllerian hormone: A novel biomarker for detecting bovine freemartinism

“…Yet, infertility or subfertility significantly impedes sustainable cattle production, particularly in heifers. The failure of heifers to conceive and produce a calf within an optimal timeframe is a pivotal factor influencing the profitability and long-term viability of the cattle industry (Marrella & Biase, 2023). Simultaneously, heifers serve as an exceptional biomedical model for delving into the fundamental causes of infertility.…”

“…Distinguishing between fertile and infertile heifers is of utmost importance for farms. Therefore, carefully selecting heifers is pivotal for ensuring the overall profitability and sustainability of the cowheifer sector (Kertz et al, 2023;Marrella & Biase, 2023).…”