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

Souhrn

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


Zdroje

1. Fowden AL, Moore T. Maternal-fetal resource allocation: Co-operation and conflict. Placenta. 2012;33(SUPPL 2):e11–5.

2. Cross JC. Adaptability and potential for treatment of placental functions to improve embryonic development and postnatal health. Reprod Fertil Dev. 2016;28(1–2):75–82. doi: 10.1071/RD15342 27062876

3. Romo A, Raquel C, Javier T. Intrauterine growth retardation (IUGR): epidemiology and etiology. Pediatr Endocrinol Rev. 2009;6(3):332–6.

4. Gaccioli F, Lager S, Powell TL, Jansson T. Placental transport in response to altered maternal nutrition. J Dev Orig Health Dis. 2013;4(2):101–15. doi: 10.1017/S2040174412000529 25054676

5. Prada J, Tsang R. Biological mechanisms of environmentally induced causes of IUGR. Eur J Clin Nutr. 1998;52 Suppl 1:S21–7; discussion S27-8.

6. Barker D, Eriksson J, Forsen T, Osmond C. Fetal origins of adult disease: strength of effects and biological basis. Int J Epidemiol. 2002;31:1235–9. doi: 10.1093/ije/31.6.1235 12540728

7. Sferruzzi-Perri AN, Camm EJ. The programming power of the placenta. Front Physiol. 2016;7:7:33. doi: 10.3389/fphys.2016.00007

8. Fowden AL, Sferruzzi-Perri AN, Coan PM, Constancia M, Burton GJ. Placental efficiency and adaptation: endocrine regulation. J Physiol. 2009 Jul 15;587(Pt 14):3459–72. doi: 10.1113/jphysiol.2009.173013 19451204

9. Morrison JL. Sheep models of intrauterine growth restriction: Fetal adaptations and consequences. Clin Exp Pharmacol Physiol. 2008;35(7):730–43. doi: 10.1111/j.1440-1681.2008.04975.x 18498533

10. Coan PM, Conroy N, Burton GJ, Ferguson-Smith AC. Origin and characteristics of glycogen cells in the developing murine placenta. Dev Dyn. 2006;235(12):3280–94. doi: 10.1002/dvdy.20981 17039549

11. Coan PM, Ferguson-Smith AC, Burton GJ. Developmental Dynamics of the Definitive Mouse Placenta Assessed by Stereology. Biol Reprod. 2004;70(6):1806–13. doi: 10.1095/biolreprod.103.024166 14973263

12. Simmons DG, Fortier AL, Cross JC. Diverse subtypes and developmental origins of trophoblast giant cells in the mouse placenta. Dev Biol. 2007;304(2):567–78. doi: 10.1016/j.ydbio.2007.01.009 17289015

13. Watson E, Cross J. Development of Structures and Transport Functions in the Mouse Placenta. Physiology. 2005;20:180–93. doi: 10.1152/physiol.00001.2005 15888575

14. Tunster S. J, Tycko B, John RM. The Imprinted Phlda2 Gene Regulates Extraembryonic Energy Stores. Mol Cell Biol. 2010;30(1):295–306. doi: 10.1128/MCB.00662-09 19884348

15. Simmons DG, Rawn S, Davies A, Hughes M, Cross JC. Spatial and temporal expression of the 23 murine Prolactin/Placental Lactogen-related genes is not associated with their position in the locus. BMC Genomics. 2008;9:352. doi: 10.1186/1471-2164-9-352 18662396

16. Soares MJ, Konno T, Alam SMK. The prolactin family: effectors of pregnancy-dependent adaptations. Trends Endocrinol Metab. 2007;18(3):114–21. doi: 10.1016/j.tem.2007.02.005 17324580

17. Sferruzzi-Perri AN. Regulating needs: Exploring the role of insulin-like growth factor-2 signalling in materno-fetal resource allocation. Placenta. 2018;33:S16–22.

18. Cross JC. More of a Good Thing or Less of a Bad Thing: Gene Copy Number Variation in Polyploid Cells of the Placenta. Bartolomei MS, editor. PLoS Genet. 2014 May 1;10(5):e1004330. doi: 10.1371/journal.pgen.1004330 24784435

19. Hannibal RL, Chuong EB, Rivera-Mulia JC, Gilbert DM, Valouev A. Copy Number Variation Is a Fundamental Aspect of the Placental Genome. PLoS Genet. 2014;10(5):1004290.

20. Hannibal RL, Baker JC. Selective Amplification of the Genome Surrounding Key Placental Genes in Trophoblast Giant Cells. Curr Biol. 2016;26(2):230–6. doi: 10.1016/j.cub.2015.11.060 26774788

21. Coan PM, Vaughan OR, Mccarthy J, Mactier C, Burton GJ, Constância M, et al. Dietary composition programmes placental phenotype in mice. J Physiol. 2011;58914(589):3659–367014.

22. Coan PM, Vaughan OR, Sekita Y, Finn SL, Burton GJ, Constancia M, et al. Adaptations in placental phenotype support fetal growth during undernutrition of pregnant mice. J Physiol. 2010;588(Pt 3):527–38. doi: 10.1113/jphysiol.2009.181214 19948659

23. Fernandez-Twinn DS, Ozanne SE, Ekizoglou S, Doherty C, James L, Gusterson B, et al. The maternal endocrine environment in the low-protein model of intra-uterine growth restriction. Br J Nutr. 2003 Oct 9;90(04):815.

24. Rebelato HJ, Esquisatto MAM, Moraes C, Amaral MEC, Catisti R. Gestational protein restriction induces alterations in placental morphology and mitochondrial function in rats during late pregnancy. J Mol Histol. 2013;44(6):629–37. doi: 10.1007/s10735-013-9522-7 23884563

25. Schulz LC, Schlitt JM, Caesar G, Pennington KA. Leptin and the Placental Response to Maternal Food Restriction During Early Pregnancy in Mice. Biol Reprod. 2012;87(5):120–120. doi: 10.1095/biolreprod.112.103218 22993381

26. Strakovsky RS, Zhou D, Pan Y. A low-protein diet during gestation in rats activates the placental mammalian amino acid response pathway and programs the growth capacity of offspring. J Nutr. 2010;140(12):2116–20. doi: 10.3945/jn.110.127803 20980649

27. Langley-Evans SC, Phillips GJ, Jackson AA. Fetal Exposure to Low Protein Diet Alters the Susceptibility of Young Adult Rats to Sulfur Dioxide-Induced Lung Injury. Vol. 127, J. Nutr. 1997.

28. Gonzalez PN, Gasperowicz M, Barbeito-Andrés J, Klenin N, Cross JC, Hallgrímsson B. Chronic protein restriction in mice impacts placental function and maternal body weight before fetal growth. PLoS One. 2016;11(3):1–18.

29. Gabory A, Ferry L, Fajardy I, Jouneau L, Gothié J-D, Vigé A, et al. Maternal Diets Trigger Sex-Specific Divergent Trajectories of Gene Expression and Epigenetic Systems in Mouse Placenta. Aguila MB, editor. PLoS One. 2012 Nov 5;7(11):e47986. doi: 10.1371/journal.pone.0047986 23144842

30. Cuffe JSM, Walton SL, Singh RR, Spiers JG, Bielefeldt-Ohmann H, Wilkinson L, et al. Mid-to late term hypoxia in the mouse alters placental morphology, glucocorticoid regulatory pathways and nutrient transporters in a sex-specific manner. Authors J Physiol C. 2014;592:3127–41.

31. Ishikawa H, Ine Rattigan A´, Fundele R, Burgoyne PS. Effects of Sex Chromosome Dosage on Placental Size in Mice 1. Biol Reprod. 2003;69:483–8. doi: 10.1095/biolreprod.102.012641 12700203

32. Coan PM, Angiolini E, Sandovici I, Burton GJ, Constância M, Fowden AL. Adaptations in placental nutrient transfer capacity to meet fetal growth demands depend on placental size in mice. J Physiol. 2008;586(18):4567–76. doi: 10.1113/jphysiol.2008.156133 18653658

33. Gallou-Kabani C, Gabory A, Rg Tost J, Karimi M, Mayeur S, Lesage J, et al. Sex-and Diet-Specific Changes of Imprinted Gene Expression and DNA Methylation in Mouse Placenta under a High-Fat Diet. PLoS One. 2010;5(12):e14398. doi: 10.1371/journal.pone.0014398 21200436

34. Mao J, Zhang X, Sieli PT, Falduto MT, Torres KE, Rosenfeld CS, et al. Contrasting effects of different maternal diets on sexually dimorphic gene expression in the murine placenta. Proc Natl Acad Sci. 2010;107(12):5557–62. doi: 10.1073/pnas.1000440107 20212133

35. Chen P-Y, Ganguly A, Rubbi L, Orozco LD, Morselli M, Ashraf D, et al. Intrauterine calorie restriction affects placental DNA methylation and gene expression. Physiol Genomics. 2013;45(14):565–76. doi: 10.1152/physiolgenomics.00034.2013 23695884

36. Zambrano E, Bautista CJ, Deás M, Martínez-Samayoa PM, González-Zamorano M, Ledesma H, et al. A low maternal protein diet during pregnancy and lactation has sex- and window of exposure-specific effects on offspring growth and food intake, glucose metabolism and serum leptin in the rat. J Physiol. 2006;571(Pt 1):221–30. doi: 10.1113/jphysiol.2005.100313 16339179

37. Gao H, Sathishkumar KR, Yallampalli U, Balakrishnan M, Li X, Wu G, et al. Maternal protein restriction regulates IGF2 system in placental labyrinth. Front Biosci (Elite Ed). 2012;4:1434–50.

38. Gundersen HJG, Jensen EB. The efficiency of systematic sampling in stereology and its prediction*. J Microsc. 1986;147(September):229–63.

39. Gasperowicz M, Surmann-Schmitt C, Hamada Y, Otto F, Cross JC. The transcriptional co-repressor TLE3 regulates development of trophoblast giant cells lining maternal blood spaces in the mouse placenta. Dev Biol. 2013;382(1):1–14. doi: 10.1016/j.ydbio.2013.08.005 23954203

40. Johansson S, Wide M, Young E, Lindblad P. Expression of alkaline phosphatase in the mature mouse placenta visualized by in situ hybridization and enzyme histochemistry. Vol. 187, Anat Embryol. 1993.

41. Pimentel H, Bray NL, Puente S, Melsted P, Pachter L. Differential analysis of rna-seq incorporating quantification uncertainty. Nat Methods. 2017;14(7):687–90. doi: 10.1038/nmeth.4324 28581496

42. Yi L, Pimentel H, Bray NL, Pachter L. Gene-level differential analysis at transcript-level resolution. Genome Biol. 2018;19(53).

43. Yu G, He Q-Y. ReactomePA: an R/Bioconductor package for reactome pathway analysis and visualization. Mol BioSyst. 2016;12:477. doi: 10.1039/c5mb00663e 26661513

44. Yu G, Wang L-G, Han Y, He Q-Y. clusterProfiler: an R Package for Comparing Biological Themes Among Gene Clusters. Omi A J Integr Biol. 2012;16(5):284–7.

45. Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R, Chao P, et al. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res. 2010;38(Web Server Issue).

46. Mayhew TM. A stereological perspective on placental morphology in normal and complicated pregnancies. J Anat. 2009 Jul;215(1):77–90. doi: 10.1111/j.1469-7580.2008.00994.x 19141109

47. Endl E, Gerdes J. The Ki-67 Protein: Fascinating Forms and an Unknown Function. Exp Cell Res. 2000 Jun 15;257(2):231–7. doi: 10.1006/excr.2000.4888 10837136

48. Hendzel MJ, Wei Y, Mancini MA, Van Hooser A, Ranalli T, Brinkley B, et al. Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation. Vol. 106, Chromosoma. Springer-Verlag; 1997.

49. Watson ED, Geary-Woo C, Hughes M, Cross JC. The Mrj co-chaperone mediates keratin turnover and prevents the formation of toxic inclusion bodies in trophoblast cells of the placenta. Development. 2007;134:1809–17. doi: 10.1242/dev.02843 17409114

50. Coan PM, Ferguson-Smith AC, Burton GJ. Ultrastructural changes in the interhaemal membrane and junctional zone of the murine chorioallantoic placenta across gestation. J Anat. 2005;207:783–96. doi: 10.1111/j.1469-7580.2005.00488.x 16367805

51. Barbeito-Andrés J, Castro-Fonseca E, Qiu LR, Bernal V, Henkelman RM, Gleiser PM, et al. Region-specific changes in brain size and cell composition under chronic nutrient restriction. J Exp Biol. 2019;222.

52. Jones HN, Powell TL, Jansson T. Regulation of Placental Nutrient Transport—A Review. Placenta. 2007;28(8–9):763–74. doi: 10.1016/j.placenta.2007.05.002 17582493

53. Constância M, Hemberger M, Hughes J, Dean W, Ferguson-Smith A, Fundele R, et al. Placental-specific IGF-II is a major modulator of placental and fetal growth. Nat Lett. 2002;417.

54. Sibley CP, Coan PM, Ferguson-Smith AC, Dean W, Hughes J, Smith P, et al. Placental-specific insulin-like growth factor 2 (Igf2) regulates the diffusional exchange characteristics of the mouse placenta. PNAS. 2004;101(21):8204–8. doi: 10.1073/pnas.0402508101 15150410

55. Sferruzzi-Perri AN, Vaughan OR, Coan PM, Suciu MC, Darbyshire R, Constancia M, et al. Placental-Specific Igf2 Deficiency Alters Developmental Adaptations to Undernutrition in Mice. Endocrinology. 2011;152.

56. Mayhew TM, Barker BL. Villous Trophoblast: Morphometric Perspectives on Growth, Differentiation, Turnover and Deposition of Fibrin-type Fibrinoid During Gestation. Placenta. 2001;22:628–38. doi: 10.1053/plac.2001.0700 11504531

57. Sawa H, Ukita H, Fukuda M, Kamada H, Saito I, Öbrink B. Spatiotemporal Expression of C-CAM in the Rat Placenta. Vol. 45, The Journal of Histochemistry & Cytochemistry. 1997.

58. Adamson SL, Lu Y, Whiteley KJ, Holmyard D, Hemberger M, Pfarrer C, et al. Interactions between trophoblast cells and the maternal and fetal circulation in the mouse placenta. Dev Biol. 2002;250(2):358–73. doi: 10.1016/s0012-1606(02)90773-6 12376109

59. Zybina E V, Kudryavtseva M V, Kudryavtsev BN. Polyploidization and Endomitosis in Giant Cells of Rabbit Trophoblast. Vol. 60, Cell Tiss. Res. Springer-Verlag; 1975.

60. Zybina E V, Zybina TG. Modifications of nuclear envelope during differentiation and depolyploidization of rat trophoblast cells. Micron. 2007;39:593–606. doi: 10.1016/j.micron.2007.05.006 17627829

61. Rosenfeld CS. Sex-Specific Placental Responses in Fetal Development. Endocrinology. 2015;156(10):3422–34. doi: 10.1210/en.2015-1227 26241064

62. Eriksson JG, Kajantie E, Osmond C, Thornburg K, Barker DJP. Boys Live Dangerously in the Womb. Am J Hum Biol. 2010;22(3):330–5. doi: 10.1002/ajhb.20995 19844898

63. Higgins JS, Vaughan OR, Fernandez de Liger E, Fowden AL, Sferruzzi-Perri AN. Placental phenotype and resource allocation to fetal growth are modified by the timing and degree of hypoxia during mouse pregnancy. J Physiol. 2016;594(5):1341–56. doi: 10.1113/JP271057 26377136

64. Bouillot S, Rampon C, Tillet E, Huber P. Tracing the Glycogen Cells with Protocadherin 12 During Mouse Placenta Development. Placenta. 2006;27:882–8. doi: 10.1016/j.placenta.2005.09.009 16269175

65. Waddell BJ, Hisheh S, Dharmarajan AM, Burton PJ. Apoptosis in Rat Placenta Is Zone-Dependent and Stimulated by Glucocorticoids. Vol. 63, Biology of reproduction. 2000.

66. Dackor J, Strunk KE, Wehmeyer MM, Threadgill DW. Altered Trophoblast Proliferation is Insufficient to Account for Placental Dysfunction in Egfr Null Embryos. Placenta. 2007;28(11–12):1211–8. doi: 10.1016/j.placenta.2007.07.005 17822758

67. Fox DT, Duronio RJ. Endoreplication and polyploidy: insights into development and disease. Development. 2013;140(1):3–12. doi: 10.1242/dev.080531 23222436

68. MacAuley a, Cross JC, Werb Z. Reprogramming the cell cycle for endoreduplication in rodent trophoblast cells. Mol Biol Cell. 1998;9(4):795–807. doi: 10.1091/mbc.9.4.795 9529378

69. Hayakawa K, Terada K, Takahashi T, Oana H, Washizu M, Tanaka S. Nucleosomes of polyploid trophoblast giant cells mostly consist of histone variants and form a loose chromatin structure. Sci Reports2. 2018;8(5811).

70. Rai A, Cross JC. Three-dimensional cultures of trophoblast stem cells autonomously develop vascular-like spaces lined by trophoblast giant cells. Dev Biol. 2015;398(1):110–9. doi: 10.1016/j.ydbio.2014.11.023 25499676

71. Rawn SM, Cross JC. The Evolution, Regulation, and Function of Placenta-Specific Genes. Annu Rev Cell Dev Biol. 2008;24(1):159–81.

72. Outhwaite JE, McGuire V, Simmons DG. Genetic ablation of placental sinusoidal trophoblast giant cells causes fetal growth restriction and embryonic lethality. Placenta. 2015;36(8):951–5. doi: 10.1016/j.placenta.2015.05.013 26091829


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