Stress-induced epigenetic effects driven by maternal lactation in dairy cattle: a comethylation network approach

ABSTRACT

Epigenetic marks do not follow the Mendelian laws of inheritance. The environment can alter the epigenotype of an individual when exposed to different external stressors. In lactating cows, the first stages of gestation overlap with the lactation peak, creating a negative energy balance that is difficult to overcome with diet. This negative energy balance could affect early embryo development that must compete with the mammary tissue for nutrients. We hypothesize that the methylation profiles of calves born to nonlactating heifers are different from those of calves born to lactating cows. We found 50,277 differentially methylated cytosines and 2,281 differentially methylated regions between these two groups of animals. A comethylation network was constructed to study the correlation between the phenotypes of the mothers and the epigenome of the calves, revealing 265 regions associated with the phenotypes. Our study revealed the presence of DMCs and DMRs in calves gestated by heifers and lactating cows, which were linked to the dam’s lactation and the calves’ ICAP and milk EBV. Gene-specific analysis highlighted associations with vasculature and organ morphogenesis and cell communication and signalling. These finding support the hypothesis that calves gestated by nonlactating mothers have a different methylation profile than those gestated by lactating cows.

KEYWORDS:

• Comethylation network
• whole-genome methylation
• differential methylation
• dairy cattle epigenetics
• methylation biomarkers

Acknowledgments

The authors acknowledge the ideas and help of Juliana Afonso and Laercio R. Porto-Neto during the experimental design of the analyses. A. Lopez-Catalina’s research stay at CSIRO was funded by his predoctoral fellowship from the Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (FPI-SGIT2018-03). The data were also analysed using the CESGA Supercomputing Infrastructure (Galicia, Spain).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

ALC and LTN base called the data. ALC performed the analyses and wrote the first version of the manuscript. AR, OGR, PAA and LTN supervised the analyses and reviewed and edited the paper. All authors conceived the study and designed the experiments. OGR and AR contributed to the acquisition of funding and resources. All the authors have read and approved the final manuscript.

Availability of data and materials

The datasets generated and/or analysed during the current study are available in the National Center for Biotechnology Information (NCBI) repository under the accession number PRJNA981322.

Competing interests

The authors declare that they have no competing interests.

Ethics approval

The Ethics Committee of the Instituto Nacional de Investigación y Tecnología Agraría y Alimentaria (INIA) waived the need for ethics approval and the need to obtain consent for the collection, analysis and publication of the retrospectively obtained and anonymized data for this noninterventional study with reference CEEA-PH-2021-08. All methods were carried out in accordance with relevant guidelines and regulations from the European Union and were reported in accordance with the ARRIVE guidelines.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15592294.2024.2381856

Additional information

Funding

A. Lopez-Catalina predoctoral fellowship from Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, (FPI-SGIT2018-03).This project received funding from the European Union’s Horizon 2020 Research and Innovation Program under grant agreement no. 101000226.The authors thank the CRUE-CSIC agreement with Taylor & Francis Group for providing open access funding.