An enriched maternal environment and stereotypies of sows differentially affect the neuro-epigenome of brain regions related to emotionality in their piglets

ABSTRACT

Epigenetic mechanisms are important modulators of neurodevelopmental outcomes in the offspring of animals challenged during pregnancy. Pregnant sows living in a confined environment are challenged with stress and lack of stimulation which may result in the expression of stereotypies (repetitive behaviours without an apparent function). Little attention has been devoted to the postnatal effects of maternal stereotypies in the offspring. We investigated how the environment and stereotypies of pregnant sows affected the neuro-epigenome of their piglets. We focused on the amygdala, frontal cortex, and hippocampus, brain regions related to emotionality, learning, memory, and stress response. Differentially methylated regions (DMRs) were investigated in these brain regions of male piglets born from sows kept in an enriched vs a barren environment. Within the latter group of piglets, we compared the brain methylomes of piglets born from sows expressing stereotypies vs sows not expressing stereotypies. DMRs emerged in each comparison. While the epigenome of the hippocampus and frontal cortex of piglets is mainly affected by the maternal environment, the epigenome of the amygdala is mainly affected by maternal stereotypies. The molecular pathways and mechanisms triggered in the brains of piglets by maternal environment or stereotypies are different, which is reflected on the differential gene function associated to the DMRs found in each piglets’ brain region . The present study is the first to investigate the neuro-epigenomic effects of maternal enrichment in pigs’ offspring and the first to investigate the neuro-epigenomic effects of maternal stereotypies in the offspring of a mammal.

KEYWORDS:

• Maternal environment
• stereotypies
• prenatal
• offspring
• brain
• emotionality
• epigenetics
• DNA methylation

Acknowledgments

This project was sponsored with a grant awarded to AJZ from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), process number 2018/01082-04. PT received a scholarship from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brazil (CAPES) – (CAPES/PROEX). TB received a scholarship from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) under the process number 2017/05604-2. We are grateful to the Department of Preventive Veterinary Medicine and Animal Health. We are also grateful to Araporanga Farm for helping with the provision of animals. Humane Farm Animal Care is acknowledged and Vedovati, for support during the field studies. Luana Alves and Anna Cristina Oliveira helped with the experiment. CCB appreciates funding from the Swedish Research Council for Sustainable Development (FORMAS) grants #2018-01074, #2017-00946, and #2021-00532 and a grant by ‘The Escher Fund for Autism’ (CA, USA). FP appreciates funding from FAPESP projects #2016/20440-3 and #2018/13600-0 and from the Svenska Forskningsrådet FORMAS grant #2021-00532. The authors acknowledge support from the National Genomics Infrastructure in Stockholm funded by the Science for Life Laboratory, the Knut and Alice Wallenberg Foundation, and the Swedish Research Council. Likewise, the authors appreciate the computational resources provided by the SNIC/Uppsala Multidisciplinary Center for Advanced Computational Science, for assistance with massive parallel sequencing and for access to the UPPMAX computational infrastructure. We appreciate the work of Lisa Martin in language editing, and of Emmanouil Tsakoumis in reference formatting. Thanks to Professor Luiz Lehmann Coutinho, and his team from the Functional Genomics Center at Agriculture College Luiz de Queiroz, ESALQ/USP for performing the DNA sequencing.

Author contributions

Conceptualization: P.T., A.J.Z.; Methodology: P.T., A.J.Z., F.P., C.G.B., T.B.; Formal analysis: F.P.; Resources: A.J.Z., C.G.B.; Writing – original draft: P.T. and F.P. Writing – review & editing: P.T., F.P., A.J.Z., C.G.B., R.Z., T.B.; Writing – final draft: C.G.B. and A.J.Z. Supervision: A.J.Z., C.G.B.; Project administration: P.T., A.J.Z.; Funding acquisition: A.J.Z., C.G.B.

Data availability statement

The dataset supporting the conclusions of this article is available from the European Nucleotide Archive (ENA) repository (EMBL-EBI), under the accession number PRJEB51504 (www.ebi.ac.uk/ena/data/view/PRJEB51504).

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15592294.2023.2196656

Additional information

Funding

This work was sponsored through the Regular Project #2018/01082-04, financed by the Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP, granted to AJZ. PT was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior [CAPES/ PROEX - 760/2020]; FP appreciates funding from FAPESP projects #2016/20440-3 and #2018/13600-0 and from the Svenska Forskningsrådet FORMAS grant #2021-00532. TB was sponsored by the FAPESP, grant #2017/05604-2; CB appreciates funding from the Svenska Forskningsrådet Formas grant #2018-01074 and grant #2017- 00946; AJZ was sponsored by the Council for Scientific and Technological Development (CNPq), Project #316457/2021-3.