Complex patterns of cell growth in the placenta in normal pregnancy and as adaptations to maternal diet restriction

Autoři: Malcolm Eaton aff001;  Alastair H. Davies aff002;  Jay Devine aff003;  Xiang Zhao aff001;  David G. Simmons aff002;  Elín Maríusdóttir aff002;  David R. C. Natale aff002;  John R. Matyas aff002;  Elizabeth A. Bering aff001;  Matthew L. Workentine aff004;  Benedikt Hallgrimsson aff003;  James C. Cross aff001
Působiště autorů: Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary Alberta aff001;  Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary Alberta aff002;  Department of Anatomy and Cell Biology, Cumming School of Medicine, University of Calgary, Calgary Alberta aff003;  Faculty of Veterinary Medicine, University of Calgary, Calgary Alberta aff004
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226735


The major milestones in mouse placental development are well described, but our understanding is limited to how the placenta can adapt to damage or changes in the environment. By using stereology and expression of cell cycle markers, we found that the placenta grows under normal conditions not just by hyperplasia of trophoblast cells but also through extensive polyploidy and cell hypertrophy. In response to feeding a low protein diet to mothers prior to and during pregnancy, to mimic chronic malnutrition, we found that this normal program was altered and that it was influenced by the sex of the conceptus. Male fetuses showed intrauterine growth restriction (IUGR) by embryonic day (E) 18.5, just before term, whereas female fetuses showed IUGR as early as E16.5. This difference was correlated with differences in the size of the labyrinth layer of the placenta, the site of nutrient and gas exchange. Functional changes were implied based on up-regulation of nutrient transporter genes. The junctional zone was also affected, with a reduction in both glycogen trophoblast and spongiotrophoblast cells. These changes were associated with increased expression of Phlda2 and reduced expression of Egfr. Polyploidy, which results from endoreduplication, is a normal feature of trophoblast giant cells (TGC) but also spongiotrophoblast cells. Ploidy was increased in sinusoidal-TGCs and spongiotrophoblast cells, but not parietal-TGCs, in low protein placentas. These results indicate that the placenta undergoes a range of changes in development and function in response to poor maternal diet, many of which we interpret are aimed at mitigating the impacts on fetal and maternal health.

Klíčová slova:

Blood – Cell cycle and cell division – Diet – Gene expression – Chorion – Pregnancy – Placenta – Trophoblasts


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