Characterization of immune pleiotropy of ESR1 gene in pigs
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ORIGINAL ARTICLE
Characterization of immune pleiotropy of ESR1 gene in pigs Yalan Wu1 · Wei Zhang1 · lingni Zhang1 · Daoyuan Wang1 · Shuhong Zhao1,2 · Mengjin Zhu1,2 Received: 11 July 2020 / Accepted: 12 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract It is well known that the estrogen receptor alpha gene (ESR1) affects the reproductive traits of pigs; however, the immune role of ESR1 gene has not yet been resolved. Here, we characterized the pleiotropic aspects of ESR1 gene in immunity using the pig model. Tissue expression profile showed that the ESR1 gene had a broad ectopic expression in multiple reproductive and immune-related tissues/organs, which provided the tissue-level spatial fundamental of ESR1 gene that might function as a pleiotropic immune regulator. Using the peripheral blood cell model, a coupling transcriptome analytical strategy was proposed and verified that there existed strong positive or negative correlations of ESR1 gene with hundreds of differentially expressed genes that were involved in the immune regulation, indicating that the ESR1 gene might affect or be affected by, directly or indirectly, dozens of immune-related genes in the peripheral blood cells. Furthermore, the results of genetic association analysis showed that the SmaI-polymorphism of ESR1 gene had significant or highly significant associations with multiple immune traits, including platelet (PLT), hematocrit (HCT), the number of CD4-CD8-CD3- cells, plateletcrit (PCT), mean corpuscular volume (MCV), and mean corpuscular hemoglobin concentration (MCHC). Multiple evidences supported the immune pleiotropic roles of ESR1 gene in pigs. The study advances our understanding of the cross-species immune pleiotropic landscape of ESR1 gene and also provides a potential pleiotropic molecular marker for disease-resistant breeding in pigs. Keywords ESR1 · Immune pleiotropy · Coupling transcriptome · Interaction network · Genetic association · Pig
Introduction Estrogen plays wide roles in reproductive regulations, and numerous studies have documented that the reproductive estrogen also interacts with diverse non-reproductive physiology such as immunity (Khan et al. 2012; Hamilton et al. 2017). Involving both innate and adaptive immune cells, the immune system provides many natural targets for estrogen Yalan Wu and Wei Zhang contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00251-020-01178-2) contains supplementary material, which is available to authorized users. * Mengjin Zhu [email protected] 1
Key Lab of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China
The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan 430070, China
2
action (Deena et al. 2016). The estrogen has been confirmed to regulate neutrophil numbers and function (Cuzzocrea et al. 2008; Li et al. 201
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