Quantification of fetal organ sparing in maternal low-protein dietary models [version 2; peer review: 2 approved]
Background: Maternal malnutrition can lead to fetal growth restriction. This is often associated with organ sparing and long-lasting physiological dysfunctions during adulthood, although the underlying mechanisms are not yet well understood. Methods: Low protein (LP) dietary models in C57BL/6J mice...
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| Format: | Article |
| Language: | English |
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Wellcome
2022-05-01
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| Series: | Wellcome Open Research |
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| Online Access: | https://wellcomeopenresearch.org/articles/6-218/v2 |
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| author | Eva Islimye Ying Zhang Alex P. Gould Sarah Hart-Johnson Patricia Serpente |
| author_facet | Eva Islimye Ying Zhang Alex P. Gould Sarah Hart-Johnson Patricia Serpente |
| author_sort | Eva Islimye |
| collection | DOAJ |
| description | Background: Maternal malnutrition can lead to fetal growth restriction. This is often associated with organ sparing and long-lasting physiological dysfunctions during adulthood, although the underlying mechanisms are not yet well understood. Methods: Low protein (LP) dietary models in C57BL/6J mice were used to investigate the proximal effects of maternal malnutrition on fetal organ weights and organ sparing at embryonic day 18.5 (E18.5). Results: Maternal 8% LP diet induced strikingly different degrees of fetal growth restriction in different animal facilities, but adjustment of dietary protein content allowed similar fetal body masses to be obtained. A maternal LP diet that restricted fetal body mass by 40% did not decrease fetal brain mass to the same extent, reflecting positive growth sparing of this organ. Under these conditions, fetal pancreas and liver mass decreased by 60-70%, indicative of negative organ sparing. A series of dietary swaps between LP and standard diets showed that the liver is capable of efficient catch-up growth from as late as E14.5 whereas, after E10.5, the pancreas is not. Conclusions: This study highlights that the reproducibility of LP fetal growth restriction studies between laboratories can be improved by careful calibration of maternal dietary protein content. LP diets that induce 30-40% restriction of prenatal growth provide a good model for fetal organ sparing. For the liver, recovery of growth following protein restriction is efficient throughout fetal development but, for the pancreas, transient LP exposures spanning the progenitor expansion phase lead to an irreversible fetal growth deficit. |
| first_indexed | 2024-12-10T21:31:16Z |
| format | Article |
| id | doaj.art-4b0c0811c07f4257aa6f50212cb3c817 |
| institution | Directory Open Access Journal |
| issn | 2398-502X |
| language | English |
| last_indexed | 2024-12-10T21:31:16Z |
| publishDate | 2022-05-01 |
| publisher | Wellcome |
| record_format | Article |
| series | Wellcome Open Research |
| spelling | doaj.art-4b0c0811c07f4257aa6f50212cb3c8172022-12-22T01:32:47ZengWellcomeWellcome Open Research2398-502X2022-05-01619785Quantification of fetal organ sparing in maternal low-protein dietary models [version 2; peer review: 2 approved]Eva Islimye0https://orcid.org/0000-0002-9131-7956Ying Zhang1https://orcid.org/0000-0003-2194-7116Alex P. Gould2https://orcid.org/0000-0002-6875-6985Sarah Hart-Johnson3Patricia Serpente4https://orcid.org/0000-0002-7485-1161Laboratory of Physiology and Metabolism, The Francis Crick Institute, London, NW1 1AT, UKLaboratory of Physiology and Metabolism, The Francis Crick Institute, London, NW1 1AT, UKLaboratory of Physiology and Metabolism, The Francis Crick Institute, London, NW1 1AT, UKMRC National Institute for Medical Research, UK, Mill Hill, London, NW7 1AA, UKLaboratory of Physiology and Metabolism, The Francis Crick Institute, London, NW1 1AT, UKBackground: Maternal malnutrition can lead to fetal growth restriction. This is often associated with organ sparing and long-lasting physiological dysfunctions during adulthood, although the underlying mechanisms are not yet well understood. Methods: Low protein (LP) dietary models in C57BL/6J mice were used to investigate the proximal effects of maternal malnutrition on fetal organ weights and organ sparing at embryonic day 18.5 (E18.5). Results: Maternal 8% LP diet induced strikingly different degrees of fetal growth restriction in different animal facilities, but adjustment of dietary protein content allowed similar fetal body masses to be obtained. A maternal LP diet that restricted fetal body mass by 40% did not decrease fetal brain mass to the same extent, reflecting positive growth sparing of this organ. Under these conditions, fetal pancreas and liver mass decreased by 60-70%, indicative of negative organ sparing. A series of dietary swaps between LP and standard diets showed that the liver is capable of efficient catch-up growth from as late as E14.5 whereas, after E10.5, the pancreas is not. Conclusions: This study highlights that the reproducibility of LP fetal growth restriction studies between laboratories can be improved by careful calibration of maternal dietary protein content. LP diets that induce 30-40% restriction of prenatal growth provide a good model for fetal organ sparing. For the liver, recovery of growth following protein restriction is efficient throughout fetal development but, for the pancreas, transient LP exposures spanning the progenitor expansion phase lead to an irreversible fetal growth deficit.https://wellcomeopenresearch.org/articles/6-218/v2Fetal growth restriction Developmental origins of health and disease (DOHaD) Small for gestational age (SGA) Intrauterine growth restriction (IUGR) Organ sparing Brain sparingeng |
| spellingShingle | Eva Islimye Ying Zhang Alex P. Gould Sarah Hart-Johnson Patricia Serpente Quantification of fetal organ sparing in maternal low-protein dietary models [version 2; peer review: 2 approved] Wellcome Open Research Fetal growth restriction Developmental origins of health and disease (DOHaD) Small for gestational age (SGA) Intrauterine growth restriction (IUGR) Organ sparing Brain sparing eng |
| title | Quantification of fetal organ sparing in maternal low-protein dietary models [version 2; peer review: 2 approved] |
| title_full | Quantification of fetal organ sparing in maternal low-protein dietary models [version 2; peer review: 2 approved] |
| title_fullStr | Quantification of fetal organ sparing in maternal low-protein dietary models [version 2; peer review: 2 approved] |
| title_full_unstemmed | Quantification of fetal organ sparing in maternal low-protein dietary models [version 2; peer review: 2 approved] |
| title_short | Quantification of fetal organ sparing in maternal low-protein dietary models [version 2; peer review: 2 approved] |
| title_sort | quantification of fetal organ sparing in maternal low protein dietary models version 2 peer review 2 approved |
| topic | Fetal growth restriction Developmental origins of health and disease (DOHaD) Small for gestational age (SGA) Intrauterine growth restriction (IUGR) Organ sparing Brain sparing eng |
| url | https://wellcomeopenresearch.org/articles/6-218/v2 |
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