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

Morgan, Hannah L.; Aljumah, Arwa; Rouillon, Charl�ne; Watkins, Adam J.

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 Dnmt3b expression, 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.

Citation

Morgan, H. L., Aljumah, A., Rouillon, C., & Watkins, A. J. (2021). Paternal low protein diet and the supplementation of methyl-donors impact fetal growth and placental development in mice. Placenta, 103, 124-133. https://doi.org/10.1016/j.placenta.2020.10.020

• Journal Article Type: Article
• Acceptance Date: Oct 16, 2020
• Online Publication Date: Oct 17, 2020
• Publication Date: Jan 1, 2021
• Deposit Date: Oct 20, 2020
• Publicly Available Date: Oct 18, 2021
• Journal: Placenta
• Print ISSN: 0143-4004
• Electronic ISSN: 1532-3102
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 103
• Pages: 124-133
• DOI: https://doi.org/10.1016/j.placenta.2020.10.020
• Keywords: Obstetrics and Gynaecology; Developmental Biology; Reproductive Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/4977764
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0143400420304173