Combining Transcriptomics and Proteomics to Screen Candidate Genes Related to Bovine Birth Weight

TL;DR

This study combines gene and protein analysis to find genes linked to calf birth weight in cattle, revealing how placental function affects fetal growth.

Contribution

The study identifies novel candidate genes and proteins in bovine placentae that influence calf birth weight through lipid and energy metabolism.

Findings

High-birth-weight calves have placentae with enhanced nutrient transport and lipid synthesis genes.

Low-birth-weight calves prioritize cell proliferation and angiogenesis in placental function.

ELOVL5, ELOVL7, ACSL1, CYP11A1, and CYP17A1 are proposed as potential biomarkers for regulating calf birth weight.

Abstract

The growth and development of fetal calves depend on nutrients from maternal circulation through the placenta, which can directly impact offspring health in early or later life. In this study, we examined how the placenta regulates calf birth weight using transcriptomic and proteomic analyses, identifying candidate genes associated with this trait. Our results indicate that a key factor affecting calf birth weight is that the placenta of high-birth-weight (HB) calves supplies more nutrients to the fetus at the transcriptomic level, characterized by enhanced nutrient transport, energy metabolism, and lipid synthesis. However, placentae from low-birth-weight (LB) calves focus more on cell proliferation and angiogenesis. At the protein level, differences in calf birth weight among Shandong Black cattle primarily arise from the energy metabolism and lipid synthesis processes while also showing significant disparities in immune function. Integrated analysis suggests that increased calf birth weight in the HB group results from efficient energy production and lipid synthesis by their placentae along with optimized cholesterol biosynthesis and metabolic pathways. Finally, we propose ELOVL5, ELOVL7, ACSL1, CYP11A1, and CYP17A1 as potential protein biomarkers that modulate the fatty acid metabolism, lipid synthesis, and cholesterol levels to influence calf birth weight.

The placenta is a vital organ in bovine reproduction, crucial for blood supply, nutrient transport, and embryonic development. It plays an essential role in the intrauterine growth of calves. However, the molecular mechanisms governing placental function in calves remain inadequately understood. Methods: We established transcriptome and proteome databases for low-birth-weight (LB) and high-birth-weight (HB) calf placentae, identifying key genes and proteins associated with birth weight through bioinformatics analyses that included functional enrichment and protein–protein interactions (PPIs). Both mRNA and protein levels were validated. Results: A total of 1494 differentially expressed genes (DEGs) and 294 differentially expressed proteins (DEPs) were identified when comparing the LB group to the HB group. Furthermore, we identified 53 genes and proteins exhibiting significant co-expression across both transcriptomic and proteomic datasets; among these, 40 were co-upregulated, 8 co-downregulated, while 5 displayed upregulation at the protein level despite downregulation at the mRNA level. Functional enrichment analyses (GO and KEGG) and protein–protein interaction (PPI) analysis indicate that, at the transcriptional level, the primary factor contributing to differences in calf birth weight is that the placenta of the high-birth-weight (HB) group provides more nutrients to the fetus, characterized by enhanced nutrient transport (SLC2A1 and SLC2A11), energy metabolism (ACSL1, MICALL2, PAG2, COL14A1, and ELOVL5), and lipid synthesis (ELOVL5 and ELOVL7). In contrast, the placenta of the low-birth-weight (LB) group prioritizes cell proliferation (PAK1 and ITGA3) and angiogenesis. At the protein level, while the placentae from the HB group exhibit efficient energy production and lipid synthesis, they also demonstrate reduced immunity to various diseases such as systemic lupus erythematosus and bacterial dysentery. Conversely, the LB group placentae excel in regulating critical biological processes, including cell migration, proliferation, differentiation, apoptosis, and signal transduction; they also display higher disease immunity markers (COL6A1, TNC CD36, CD81, Igh-1a, and IGHG) compared to those of the HB group placentae. Co-expression analysis further suggests that increases in calf birth weight can be attributed to both high-efficiency energy production and lipid synthesis within the HB group placentae (ELOVL5, ELOVL7, and ACSL1), alongside cholesterol biosynthesis and metabolic pathways involving CYP11A1 and CYP17A1. Conclusion: We propose that ELOVL5, ELOVL7, ACSL1, CYP11A1, and CYP17A1 serve as potential protein biomarkers for regulating calf birth weight through the modulation of the fatty acid metabolism, lipid synthesis, and cholesterol levels.

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