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.
Highlights
The development of the mammalian fetus is fundamentally dependent upon successful implantation of the embryo into the uterine tissue
Previous studies have identified the cells closest to the central ectoplacental cone (EPC) explant as being proliferative stem cells (Scott et al 2000, El-Hashash & Kimber 2004), while those cells located at the outgrowth periphery display morphological characteristics of trophoblast giant cells (TGCs) and express specific markers such as PL-II, not expressed within proliferating cells (El-Hashash & Kimber 2004)
We have demonstrated elevated fetal growth at E17 in offspring derived from blastocysts transferred from low-protein diet (LPD)-fed dams into normal protein diet (NPD)-fed dams (Watkins et al 2008)
Summary
The development of the mammalian fetus is fundamentally dependent upon successful implantation of the embryo into the uterine tissue. TE cells not in direct contact with the ICM (mural TE) exit mitosis, endo-reduplicate their DNA and give rise to the primary trophoblast giant cells (TGCs). The TE cells directly overlying the ICM (polar TE) differentiate into the chorion and ectoplacental cone (EPC), from which secondary TGCs are derived (Simmons & Cross 2005)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
