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

Maternal nutrition modifies trophoblast giant cell phenotype and fetal growth in mice
Maternal nutrition modifies trophoblast giant cell phenotype and fetal growth in mice
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.
0022-4251
563-575
Watkins, Adam J.
2d535c61-2df0-4410-a1b4-3aa1be5a43bb
Lucas, Emma S.
713aa0eb-0951-4de7-8d1c-6fe1235a1c8c
Marfy-Smith, Stephanie
b93e230c-cc90-42f5-ae47-19354008d2fa
Bates, Nicola
a1c943ba-4314-45b4-8122-d6701589daf0
Kimber, Susan J.
f0e196d5-6427-44bb-bcd2-30c47e6d96ea
Fleming, Tom P.
2abf761a-e5a1-4fa7-a2c8-12e32d5d4c03
Watkins, Adam J.
2d535c61-2df0-4410-a1b4-3aa1be5a43bb
Lucas, Emma S.
713aa0eb-0951-4de7-8d1c-6fe1235a1c8c
Marfy-Smith, Stephanie
b93e230c-cc90-42f5-ae47-19354008d2fa
Bates, Nicola
a1c943ba-4314-45b4-8122-d6701589daf0
Kimber, Susan J.
f0e196d5-6427-44bb-bcd2-30c47e6d96ea
Fleming, Tom P.
2abf761a-e5a1-4fa7-a2c8-12e32d5d4c03

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. Reproduction, 149 (6), 563-575. (doi:10.1530/REP-14-0667). (PMID:25755287)

Record type: Article

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.

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Accepted/In Press date: 9 March 2015
e-pub ahead of print date: 9 March 2015
Published date: 1 June 2015
Organisations: Biomedicine

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Local EPrints ID: 402230
URI: https://eprints.soton.ac.uk/id/eprint/402230
ISSN: 0022-4251
PURE UUID: 245407dc-5ad1-4d75-89be-1baa539e62f4

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Date deposited: 03 Nov 2016 15:13
Last modified: 28 Aug 2019 18:05

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