DNA methylation and gene expression changes in mouse mammary tissue during successive lactations: part II - the impact of lactation rank

E Ivanova; C Hue-Beauvais; A Chaulot-Talmon; J Castille; J Laubier; C De Casanove; A Aubert-Frambourg; P Germon; H Jammes; F Le Provost

doi:10.1080/15592294.2023.2215620

DNA methylation and gene expression changes in mouse mammary tissue during successive lactations: part II - the impact of lactation rank

Epigenetics. 2023 Dec;18(1):2215620. doi: 10.1080/15592294.2023.2215620.

Authors

E Ivanova¹, C Hue-Beauvais¹, A Chaulot-Talmon^{2

3}, J Castille¹, J Laubier¹, C De Casanove¹, A Aubert-Frambourg^{2

3}, P Germon⁴, H Jammes^{2

3}, F Le Provost¹

Affiliations

¹ INRAE, AgroParisTech, GABI, Université Paris-Saclay, Jouy-en-Josas, France.
² UVSQ, INRAE, BREED, Université Paris-Saclay, Jouy-en-Josas, France.
³ BREED, Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort, France.
⁴ INRAE, Université de Tours, Nouzilly, France.

Abstract

Mastitis is among the main reasons women cease breastfeeding. In farm animals, mastitis results in significant economic losses and the premature culling of some animals. Nevertheless, the effect of inflammation on the mammary gland is not completely understood. This article discusses the changes to DNA methylation in mouse mammary tissue caused by lipopolysaccharide-induced inflammation after in vivo intramammary challenges and the differences in DNA methylation between 1^st and 2^nd lactations. Lactation rank induces 981 differential methylations of cytosines (DMCs) in mammary tissue. Inflammation in 1^st lactation compared to inflammation in 2^nd lactation results in the identification of 964 DMCs. When comparing inflammation in 1^st vs. 2^nd lactations with previous inflammation history, 2590 DMCs were identified. Moreover, Fluidigm PCR data show changes in the expression of several genes related to mammary function, epigenetic regulation, and the immune response. We show that the epigenetic regulation of two successive physiological lactations is not the same in terms of DNA methylation and that the effect of lactation rank on DNA methylation is stronger than that of the onset of inflammation. The conditions presented here show that few DMCs are shared between comparisons, suggesting a specific epigenetic response depending on lactation rank, the presence of inflammation, and even whether the cells had previously suffered inflammation. In the long term, this information could lead to a better understanding of the epigenetic regulation of lactation in both physiological and pathological conditions.Abbreviations: RRBS, reduced representation bisulphite sequencing; RT-qPCR, real-time quantitative polymerase chain reaction; MEC, mammary epithelial cells; MaSC, mammary stem cell; TSS, transcription start site; TTS, transcription termination site; UTR, untranslated region; SINE, short interspersed nuclear element; LINE, long interspersed nuclear element; CGI, CpG island; DEG, differentially expressed gene; DMC, differentially methylated cytosine; DMR, differentially methylated region; GO term, gene ontology term; MF, molecular function; BP, biological process.

Keywords: DNA methylation; Lactation; inflammation; mammary epithelial cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cytosine
DNA Methylation*
Epigenesis, Genetic
Female
Gene Expression
Humans
Inflammation
Lactation
Mastitis*
Mice

Substances

Cytosine

Grants and funding

This work was funded by the GISA metaprogram: LongHealth project (INRAE), the MeMoFlaMa project (APIS-GENE), and the Department of Animal Genetics (INRAE).