Mouse maternal systemic inflammation at the zygote stage causes blunted cytokine responsiveness in lipopolysaccharide-challenged adult offspring
<p>Abstract</p> <p>Background</p> <p>The preimplantation embryo is sensitive to culture conditions <it>in vitro </it>and poor maternal diet <it>in vivo</it>. Such environmental perturbations can have long-lasting detrimental consequences for offs...
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| Format: | Article |
| Language: | English |
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BMC
2011-07-01
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| Series: | BMC Biology |
| Online Access: | http://www.biomedcentral.com/1741-7007/9/49 |
| _version_ | 1811275616800997376 |
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| author | Fleming Tom P Perry V Hugh Teeling Jessica L Williams Charlotte L |
| author_facet | Fleming Tom P Perry V Hugh Teeling Jessica L Williams Charlotte L |
| author_sort | Fleming Tom P |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The preimplantation embryo is sensitive to culture conditions <it>in vitro </it>and poor maternal diet <it>in vivo</it>. Such environmental perturbations can have long-lasting detrimental consequences for offspring health and physiology. However, early embryo susceptibility to other aspects of maternal health and their potential long-term influence into adulthood is relatively unexplored. In this study, we established an <it>in vivo </it>mouse model of maternal periconceptional systemic inflammation by intraperitoneal lipopolysaccharide (LPS) administration on the day of zygote formation and investigated the consequences into adulthood.</p> <p>Results</p> <p>In the short term, maternal LPS challenge induced a transient and typical maternal sickness response (elevated serum proinflammatory cytokines and hypoactive behaviour). Maternal LPS challenge altered preimplantation embryo morphogenesis and cell lineage allocation, resulting in reduced blastocyst inner cell mass (ICM) cell number and a reduced ICM:trophectoderm cell ratio. In the long term, diverse aspects of offspring physiology were affected by maternal LPS treatment. Whilst birthweight, growth and adult blood pressure were unaltered, reduced activity in an open-field behaviour test, increased fat pad:body weight ratio and increased body mass index were observed in male, but not female, offspring. Most importantly, the maternal LPS challenge caused corticosterone-independent blunting of the serum proinflammatory cytokine response to innate immune challenge in both male and female offspring. The suppressed state of innate immunity in challenged offspring was dose-dependent with respect to the maternal LPS concentration administered.</p> <p>Conclusions</p> <p>These results demonstrate for the first time that the preimplantation embryo <it>in vivo </it>is sensitive to maternal systemic inflammation, with effects on blastocyst cell lineage allocation and consequences for behaviour, adiposity and innate immune response in adult offspring. Critically, we identify a novel mechanism mediated through maternal-embryonic interactions that confers plasticity in the development of the innate immune system, which is potentially important in setting postnatal tolerance to environmental pathogens. Our study extends the concept of developmental programming of health and disease to include maternal health at the time of conception.</p> |
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| format | Article |
| id | doaj.art-f64ca9057b754411a748d19a872c8418 |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-04-12T23:41:01Z |
| publishDate | 2011-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-f64ca9057b754411a748d19a872c84182022-12-22T03:11:59ZengBMCBMC Biology1741-70072011-07-01914910.1186/1741-7007-9-49Mouse maternal systemic inflammation at the zygote stage causes blunted cytokine responsiveness in lipopolysaccharide-challenged adult offspringFleming Tom PPerry V HughTeeling Jessica LWilliams Charlotte L<p>Abstract</p> <p>Background</p> <p>The preimplantation embryo is sensitive to culture conditions <it>in vitro </it>and poor maternal diet <it>in vivo</it>. Such environmental perturbations can have long-lasting detrimental consequences for offspring health and physiology. However, early embryo susceptibility to other aspects of maternal health and their potential long-term influence into adulthood is relatively unexplored. In this study, we established an <it>in vivo </it>mouse model of maternal periconceptional systemic inflammation by intraperitoneal lipopolysaccharide (LPS) administration on the day of zygote formation and investigated the consequences into adulthood.</p> <p>Results</p> <p>In the short term, maternal LPS challenge induced a transient and typical maternal sickness response (elevated serum proinflammatory cytokines and hypoactive behaviour). Maternal LPS challenge altered preimplantation embryo morphogenesis and cell lineage allocation, resulting in reduced blastocyst inner cell mass (ICM) cell number and a reduced ICM:trophectoderm cell ratio. In the long term, diverse aspects of offspring physiology were affected by maternal LPS treatment. Whilst birthweight, growth and adult blood pressure were unaltered, reduced activity in an open-field behaviour test, increased fat pad:body weight ratio and increased body mass index were observed in male, but not female, offspring. Most importantly, the maternal LPS challenge caused corticosterone-independent blunting of the serum proinflammatory cytokine response to innate immune challenge in both male and female offspring. The suppressed state of innate immunity in challenged offspring was dose-dependent with respect to the maternal LPS concentration administered.</p> <p>Conclusions</p> <p>These results demonstrate for the first time that the preimplantation embryo <it>in vivo </it>is sensitive to maternal systemic inflammation, with effects on blastocyst cell lineage allocation and consequences for behaviour, adiposity and innate immune response in adult offspring. Critically, we identify a novel mechanism mediated through maternal-embryonic interactions that confers plasticity in the development of the innate immune system, which is potentially important in setting postnatal tolerance to environmental pathogens. Our study extends the concept of developmental programming of health and disease to include maternal health at the time of conception.</p>http://www.biomedcentral.com/1741-7007/9/49 |
| spellingShingle | Fleming Tom P Perry V Hugh Teeling Jessica L Williams Charlotte L Mouse maternal systemic inflammation at the zygote stage causes blunted cytokine responsiveness in lipopolysaccharide-challenged adult offspring BMC Biology |
| title | Mouse maternal systemic inflammation at the zygote stage causes blunted cytokine responsiveness in lipopolysaccharide-challenged adult offspring |
| title_full | Mouse maternal systemic inflammation at the zygote stage causes blunted cytokine responsiveness in lipopolysaccharide-challenged adult offspring |
| title_fullStr | Mouse maternal systemic inflammation at the zygote stage causes blunted cytokine responsiveness in lipopolysaccharide-challenged adult offspring |
| title_full_unstemmed | Mouse maternal systemic inflammation at the zygote stage causes blunted cytokine responsiveness in lipopolysaccharide-challenged adult offspring |
| title_short | Mouse maternal systemic inflammation at the zygote stage causes blunted cytokine responsiveness in lipopolysaccharide-challenged adult offspring |
| title_sort | mouse maternal systemic inflammation at the zygote stage causes blunted cytokine responsiveness in lipopolysaccharide challenged adult offspring |
| url | http://www.biomedcentral.com/1741-7007/9/49 |
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