Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development

Development. 2018 Jan 29;145(2):dev156273. doi: 10.1242/dev.156273.

Abstract

An increasing body of evidence points to significant spatio-temporal differences in early placental development between mouse and human, but a detailed comparison of placentae in these two species is missing. We set out to compare placentae from both species across gestation, with a focus on trophoblast progenitor markers. We found that CDX2 and ELF5, but not EOMES, are expressed in early post-implantation trophoblast subpopulations in both species. Genome-wide expression profiling of mouse and human placentae revealed clusters of genes with distinct co-expression patterns across gestation. Overall, there was a closer fit between patterns observed in the placentae when the inter-species comparison was restricted to human placentae through gestational week 16 (thus, excluding full-term samples), suggesting that the developmental timeline in mouse runs parallel to the first half of human placental development. In addition, we identified VGLL1 as a human-specific marker of proliferative cytotrophoblast, where it is co-expressed with the transcription factor TEAD4. As TEAD4 is involved in trophectoderm specification in the mouse, we posit a regulatory role for VGLL1 in early events during human placental development.

Keywords: Comparative study; Cytotrophoblast; Placenta; Placental development; Placental progenitors; Trophoblast stem cells.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CDX2 Transcription Factor / genetics
  • CDX2 Transcription Factor / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Genome-Wide Association Study
  • Gestational Age
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Mice
  • Multigene Family
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Placenta / metabolism*
  • Placentation / genetics
  • Placentation / physiology*
  • Pregnancy
  • Proto-Oncogene Proteins c-ets / genetics
  • Proto-Oncogene Proteins c-ets / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Species Specificity
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • TEA Domain Transcription Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • CDX2 Transcription Factor
  • CDX2 protein, human
  • DNA-Binding Proteins
  • ELF5 protein, human
  • EOMES protein, human
  • Muscle Proteins
  • Proto-Oncogene Proteins c-ets
  • RNA, Messenger
  • T-Box Domain Proteins
  • TEA Domain Transcription Factors
  • TEAD4 protein, human
  • Transcription Factors
  • VGLL1 protein, human