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Paternal low protein diet and the supplementation of methyl-donors impact fetal growth and placental development in mice

Abstract : Introduction: Paternal low-protein diet can alter sperm methylation status, fetal growth and program offspring ill-health, however its impact on the placenta remains poorly defined. Here we examine the influence paternal low-protein diet has on fetal and placental development and the additional impact of supplementary methyl-donors on fetoplacental physiology. Methods: Male C57BL/6J mice were fed a control normal protein diet (NPD; 18% protein), a low-protein diet (LPD; 9% protein) or LPD with methyl-donor supplementation (MD-LPD; choline chloride, betaine, methionine, folic acid, vitamin B12) for a minimum of 8 weeks. Males were mated with 8-11 week old female C57BL/6J mice and fetal and placental tissue collected on embryonic day 17.5. Results: Paternal LPD was associated with increased fetal weights compared to NPD and MD-LPD with 22% fetuses being above the 90th centile for fetal weight. However, LPD and MD-LPD placental weights were reduced when compared to NPD. Placentas from LPD fathers demonstrated a reduced junctional zone area and reduced free-fatty acid content. MD-LPD placentas did not mirror these finding, demonstrating an increased chorion area, a reduction in junctional-specific glycogen staining and reduced placental Dnmt3bexpression, none of which were apparent in either NPD or LPD placentas. Discussion: A sub-optimal paternal diet can influence fetal growth and placental development, and dietary methyl-donor supplementation alters placental morphology and gene expression differentially to that observed with LPD alone. Understanding how paternal diet and micro-nutrient supplementation influence placental development is crucial for determining connections between paternal well-being and future offspring health.
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https://hal.inrae.fr/hal-03284469
Contributor : Agnès Girard <>
Submitted on : Monday, July 12, 2021 - 3:50:17 PM
Last modification on : Tuesday, August 17, 2021 - 4:00:01 PM

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Hannah Morgan, Arwa Aljumah, Charlène Rouillon, Adam Watkins. Paternal low protein diet and the supplementation of methyl-donors impact fetal growth and placental development in mice. Placenta, Elsevier, 2021, 103, pp.124-133. ⟨10.1016/j.placenta.2020.10.020⟩. ⟨hal-03284469⟩

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