In utero Exposure to Maternal Chronic Inflammation Transfers a Pro-Inflammatory Profile to Generation F2 via Sex-Specific Mechanisms
Generational transfer of maladaptations in offspring have been reported to persist for multiple generations in conditions of chronic inflammation, metabolic and psychological stress. Thus, the current study aimed to expand our understanding of the nature, potential sex specificity, and transgenerati...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00048/full |
| _version_ | 1818263424926220288 |
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| author | Rozanne Charlene McChary Adams Carine Smith |
| author_facet | Rozanne Charlene McChary Adams Carine Smith |
| author_sort | Rozanne Charlene McChary Adams |
| collection | DOAJ |
| description | Generational transfer of maladaptations in offspring have been reported to persist for multiple generations in conditions of chronic inflammation, metabolic and psychological stress. Thus, the current study aimed to expand our understanding of the nature, potential sex specificity, and transgenerational plasticity of inflammatory maladaptations resulting from maternal chronic inflammation. Briefly, F1 and F2 generations of offspring from C57/BL/6 dams exposed to a modified maternal periconception systemic inflammation (MSPI) protocol were profiled in terms of leukocyte and splenocyte counts and cytokine responses, as well as glucocorticoid sensitivity. Overall, F1 male and female LPS groups presented with glucocorticoid hypersensitivity (with elevated corticosterone and increased leukocyte glucocorticoid receptor levels) along with a pro-inflammatory phenotype, which carried over to the F2 generation. The transfer of inflammatory and glucocorticoid responsiveness from F1 to F2 is evident, with heritability of this phenotype in F2. The findings suggest that maternal (F0) perinatal chronic inflammation resulted in glucocorticoid dysregulation and a resultant pro-inflammatory phenotype, which is transferred in the maternal lineage but seems to affect male offspring to a greater extent. Of further interest, upregulation of IL-1β cytokine responses is reported in female offspring only. The cumulative maladaptation reported in F2 offspring when both F1 parents were affected by maternal LPS exposure is suggestive of immune senescence. Given the potential impact of current results and the lack of sex-specific investigations, more research in this context is urgently required. |
| first_indexed | 2024-12-12T19:18:48Z |
| format | Article |
| id | doaj.art-06b5d3838fd7464980da5d7cdc8223fc |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T19:18:48Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-06b5d3838fd7464980da5d7cdc8223fc2022-12-22T00:14:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-02-011110.3389/fimmu.2020.00048505728In utero Exposure to Maternal Chronic Inflammation Transfers a Pro-Inflammatory Profile to Generation F2 via Sex-Specific MechanismsRozanne Charlene McChary AdamsCarine SmithGenerational transfer of maladaptations in offspring have been reported to persist for multiple generations in conditions of chronic inflammation, metabolic and psychological stress. Thus, the current study aimed to expand our understanding of the nature, potential sex specificity, and transgenerational plasticity of inflammatory maladaptations resulting from maternal chronic inflammation. Briefly, F1 and F2 generations of offspring from C57/BL/6 dams exposed to a modified maternal periconception systemic inflammation (MSPI) protocol were profiled in terms of leukocyte and splenocyte counts and cytokine responses, as well as glucocorticoid sensitivity. Overall, F1 male and female LPS groups presented with glucocorticoid hypersensitivity (with elevated corticosterone and increased leukocyte glucocorticoid receptor levels) along with a pro-inflammatory phenotype, which carried over to the F2 generation. The transfer of inflammatory and glucocorticoid responsiveness from F1 to F2 is evident, with heritability of this phenotype in F2. The findings suggest that maternal (F0) perinatal chronic inflammation resulted in glucocorticoid dysregulation and a resultant pro-inflammatory phenotype, which is transferred in the maternal lineage but seems to affect male offspring to a greater extent. Of further interest, upregulation of IL-1β cytokine responses is reported in female offspring only. The cumulative maladaptation reported in F2 offspring when both F1 parents were affected by maternal LPS exposure is suggestive of immune senescence. Given the potential impact of current results and the lack of sex-specific investigations, more research in this context is urgently required.https://www.frontiersin.org/article/10.3389/fimmu.2020.00048/fullinfectioncytokineglucocorticoid receptorgendertransgenerational inheritancepericonception systemic inflammation |
| spellingShingle | Rozanne Charlene McChary Adams Carine Smith In utero Exposure to Maternal Chronic Inflammation Transfers a Pro-Inflammatory Profile to Generation F2 via Sex-Specific Mechanisms Frontiers in Immunology infection cytokine glucocorticoid receptor gender transgenerational inheritance periconception systemic inflammation |
| title | In utero Exposure to Maternal Chronic Inflammation Transfers a Pro-Inflammatory Profile to Generation F2 via Sex-Specific Mechanisms |
| title_full | In utero Exposure to Maternal Chronic Inflammation Transfers a Pro-Inflammatory Profile to Generation F2 via Sex-Specific Mechanisms |
| title_fullStr | In utero Exposure to Maternal Chronic Inflammation Transfers a Pro-Inflammatory Profile to Generation F2 via Sex-Specific Mechanisms |
| title_full_unstemmed | In utero Exposure to Maternal Chronic Inflammation Transfers a Pro-Inflammatory Profile to Generation F2 via Sex-Specific Mechanisms |
| title_short | In utero Exposure to Maternal Chronic Inflammation Transfers a Pro-Inflammatory Profile to Generation F2 via Sex-Specific Mechanisms |
| title_sort | in utero exposure to maternal chronic inflammation transfers a pro inflammatory profile to generation f2 via sex specific mechanisms |
| topic | infection cytokine glucocorticoid receptor gender transgenerational inheritance periconception systemic inflammation |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00048/full |
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