Maternal nutrition modifies trophoblast giant cell phenotype and fetal growth in mice

Watkins, Adam J., Lucas, Emma S., Marfy-Smith, Stephanie, Bates, Nicola, Kimber, Susan J. and Fleming, Tom P. (2015). Maternal nutrition modifies trophoblast giant cell phenotype and fetal growth in mice. Human Reproduction, 149 (6), pp. 563-575.

Abstract

Mammalian placentation is dependent upon the action of trophoblast cells at the time of implantation. Appropriate fetal growth, regulated by maternal nutrition and nutrient transport across the placenta, is a critical factor for adult offspring long-term health. We have demonstrated that a mouse maternal low-protein diet (LPD) fed exclusively during preimplantation development (Emb-LPD) increases offspring growth but programmes adult cardiovascular and metabolic disease. In this study, we investigate the impact of maternal nutrition on post-implantation trophoblast phenotype and fetal growth. Ectoplacental cone explants were isolated at day 8 of gestation from female mice fed either normal protein diet (NPD: 18% casein), LPD (9% casein) or Emb-LPD and cultured in vitro. We observed enhanced spreading and cell division within proliferative and secondary trophoblast giant cells (TGCs) emerging from explants isolated from LPD-fed females when compared with NPD and Emb-LPD explants after 24 and 48 h. Moreover, both LPD and Emb-LPD explants showed substantial expansion of TGC area during 24-48 h, not observed in NPD. No difference in invasive capacity was observed between treatments using Matrigel transwell migration assays. At day 17 of gestation, LPD- and Emb-LPD-fed conceptuses displayed smaller placentas and larger fetuses respectively, resulting in increased fetal:placental ratios in both groups compared with NPD conceptuses. Analysis of placental and yolk sac nutrient signalling within the mammalian target of rapamycin complex 1 pathway revealed similar levels of total and phosphorylated downstream targets across groups. These data demonstrate that early post-implantation embryos modify trophoblast phenotype to regulate fetal growth under conditions of poor maternal nutrition.

Publication DOI: https://doi.org/10.1530/REP-14-0667
Divisions: Life & Health Sciences
Life & Health Sciences > Biosciences
Life & Health Sciences > Cell & Tissue Biomedical Research
Additional Information: © 2015 The authors. This work is licensed under a Creative Commons Attribution 3.0 Unported License. Funding: Biotechnology and Biological Sciences Research Council (BB/F007450/1; BB/I001840/1)
Uncontrolled Keywords: Obstetrics and Gynaecology,Reproductive Medicine,Embryology,Endocrinology,Cell Biology
Full Text Link: http://www.repr ... ntent/149/6/563
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2015-06-01
Authors: Watkins, Adam J.
Lucas, Emma S.
Marfy-Smith, Stephanie
Bates, Nicola
Kimber, Susan J.
Fleming, Tom P.

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