Embryonic heat conditioning induces paternal heredity of immunological cross- tolerance: coordinative role of CpG DNA methylation and miR-200a regulation
BackgroundEnhancing an organism’s survival hinges on the development of balanced and adaptable stress response systems. While the initial stress-response set-points in the hypothalamus may be genetically determined, they are further influenced by epigenetic factors during embryonic development. A de...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1487135/full |
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| author | Padma Malini Ravi Tatiana Kisliouk Shelly Druyan Amit Haron Mark A. Cline Elizabeth R. Gilbert Noam Meiri |
| author_facet | Padma Malini Ravi Tatiana Kisliouk Shelly Druyan Amit Haron Mark A. Cline Elizabeth R. Gilbert Noam Meiri |
| author_sort | Padma Malini Ravi |
| collection | DOAJ |
| description | BackgroundEnhancing an organism’s survival hinges on the development of balanced and adaptable stress response systems. While the initial stress-response set-points in the hypothalamus may be genetically determined, they are further influenced by epigenetic factors during embryonic development. A debate persists regarding the heritability of such behavioral traits. The chick in ovo heat conditioning model offers a unique insight into this fundamental question, where manipulation during embryonic development can induce heat resilience and even cross-tolerance to promote immunological resilience. In this study, we conducted an analysis of thermal manipulation during embryogenesis to demonstrate paternal heredity and investigate its transmission through sperm DNA methylation in coordination with miR-200a action.ResultFirst-generation embryos underwent in ovo heat conditioning (EHC), creating a cohort of embryonic EHC and control chicks. These chicks were then subjected to an intracranial lipopolysaccharide (LPS) challenge. Conditioning rendered the chicks immune resilient, as evidenced by their fibril effect. Male offspring were raised to maturity, and their sperm was analyzed for methylome patterns, revealing significant differences between treatments, particularly in immune and development related genes. Additionally, sperm from EHC males was used for artificial insemination of naïve Cobb hens, resulting in untreated offspring that displayed immune resilience upon LPS challenge, indicating transgenerational effects. Overlap analysis of sperm methylome and differentially methylated sites (DMS) of offspring hypothalamus revealed inheritance of altered methylation associated with specific genes. Several of these genes are potential effectors of miR-200a, whose expression profile in the hypothalamus during LPS challenge was conserved across both generations. To evaluate the role of miR-200a in cross-tolerance acquisition, miR-200a was intracranially injected, and RNA-seq analysis of the hypothalamus revealed genes involved in the regulation of developmental and metabolic processes, stress, and immune response.ConclusionThis study demonstrates paternal trait heredity by revealing that EHC induces cross-tolerance with the immunological system, rendering chicks resilient to LPS that transgenerationally transmit this to untreated offspring. Additionally, analysis of sperm methylation patterns in EHC mature chicks led to identification of genes associated with neuronal development and immune response, indicating potential neural network reorganization. Finally, miR-200a emerges as a regulator potentially involved in mediating the cross-tolerance effect. |
| format | Article |
| id | doaj-art-a430d517f369492685d159b811f97251 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-a430d517f369492685d159b811f972512025-02-07T06:49:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.14871351487135Embryonic heat conditioning induces paternal heredity of immunological cross- tolerance: coordinative role of CpG DNA methylation and miR-200a regulationPadma Malini Ravi0Tatiana Kisliouk1Shelly Druyan2Amit Haron3Mark A. Cline4Elizabeth R. Gilbert5Noam Meiri6Institute of Animal Science, Agricultural Research Organization, Volcani Center, Rishon LeZiyyon, IsraelInstitute of Animal Science, Agricultural Research Organization, Volcani Center, Rishon LeZiyyon, IsraelInstitute of Animal Science, Agricultural Research Organization, Volcani Center, Rishon LeZiyyon, IsraelInstitute of Animal Science, Agricultural Research Organization, Volcani Center, Rishon LeZiyyon, IsraelSchool of Neuroscience, Virginia Tech, Blacksburg, VA, United StatesSchool of Neuroscience, Virginia Tech, Blacksburg, VA, United StatesInstitute of Animal Science, Agricultural Research Organization, Volcani Center, Rishon LeZiyyon, IsraelBackgroundEnhancing an organism’s survival hinges on the development of balanced and adaptable stress response systems. While the initial stress-response set-points in the hypothalamus may be genetically determined, they are further influenced by epigenetic factors during embryonic development. A debate persists regarding the heritability of such behavioral traits. The chick in ovo heat conditioning model offers a unique insight into this fundamental question, where manipulation during embryonic development can induce heat resilience and even cross-tolerance to promote immunological resilience. In this study, we conducted an analysis of thermal manipulation during embryogenesis to demonstrate paternal heredity and investigate its transmission through sperm DNA methylation in coordination with miR-200a action.ResultFirst-generation embryos underwent in ovo heat conditioning (EHC), creating a cohort of embryonic EHC and control chicks. These chicks were then subjected to an intracranial lipopolysaccharide (LPS) challenge. Conditioning rendered the chicks immune resilient, as evidenced by their fibril effect. Male offspring were raised to maturity, and their sperm was analyzed for methylome patterns, revealing significant differences between treatments, particularly in immune and development related genes. Additionally, sperm from EHC males was used for artificial insemination of naïve Cobb hens, resulting in untreated offspring that displayed immune resilience upon LPS challenge, indicating transgenerational effects. Overlap analysis of sperm methylome and differentially methylated sites (DMS) of offspring hypothalamus revealed inheritance of altered methylation associated with specific genes. Several of these genes are potential effectors of miR-200a, whose expression profile in the hypothalamus during LPS challenge was conserved across both generations. To evaluate the role of miR-200a in cross-tolerance acquisition, miR-200a was intracranially injected, and RNA-seq analysis of the hypothalamus revealed genes involved in the regulation of developmental and metabolic processes, stress, and immune response.ConclusionThis study demonstrates paternal trait heredity by revealing that EHC induces cross-tolerance with the immunological system, rendering chicks resilient to LPS that transgenerationally transmit this to untreated offspring. Additionally, analysis of sperm methylation patterns in EHC mature chicks led to identification of genes associated with neuronal development and immune response, indicating potential neural network reorganization. Finally, miR-200a emerges as a regulator potentially involved in mediating the cross-tolerance effect.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1487135/fullcross-toleranceheat conditioningchickembryohypothalamusDNA methylation |
| spellingShingle | Padma Malini Ravi Tatiana Kisliouk Shelly Druyan Amit Haron Mark A. Cline Elizabeth R. Gilbert Noam Meiri Embryonic heat conditioning induces paternal heredity of immunological cross- tolerance: coordinative role of CpG DNA methylation and miR-200a regulation Frontiers in Immunology cross-tolerance heat conditioning chick embryo hypothalamus DNA methylation |
| title | Embryonic heat conditioning induces paternal heredity of immunological cross- tolerance: coordinative role of CpG DNA methylation and miR-200a regulation |
| title_full | Embryonic heat conditioning induces paternal heredity of immunological cross- tolerance: coordinative role of CpG DNA methylation and miR-200a regulation |
| title_fullStr | Embryonic heat conditioning induces paternal heredity of immunological cross- tolerance: coordinative role of CpG DNA methylation and miR-200a regulation |
| title_full_unstemmed | Embryonic heat conditioning induces paternal heredity of immunological cross- tolerance: coordinative role of CpG DNA methylation and miR-200a regulation |
| title_short | Embryonic heat conditioning induces paternal heredity of immunological cross- tolerance: coordinative role of CpG DNA methylation and miR-200a regulation |
| title_sort | embryonic heat conditioning induces paternal heredity of immunological cross tolerance coordinative role of cpg dna methylation and mir 200a regulation |
| topic | cross-tolerance heat conditioning chick embryo hypothalamus DNA methylation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1487135/full |
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