Analysis of human invasive cytotrophoblasts demonstrates mosaic aneuploidy

PLoS One. 2023 Jul 21;18(7):e0284317. doi: 10.1371/journal.pone.0284317. eCollection 2023.

Abstract

A total of 24 chromosome-specific fluorescence in situ hybridization probes for interphase nucleus analysis were developed to determine the chromosomal content of individual human invasive cytotrophoblasts derived from in vitro cultured assays. At least 75% of invasive cytotrophoblasts were hyperdiploid and the total number of chromosomes ranged from 47 to 61. The results also demonstrated that these hyperdiploid invasive cytotrophoblasts showed significant heterogeneity. The most copy number gains were observed for chromosomes 13, 14, 15, 19, 21, and 22 with average copy number greater than 2.3. A parallel study using primary invasive cytotrophoblasts also showed a similar trend of copy number changes. Conclusively, 24-chromosome analysis of human non-proliferating cytotrophoblasts (interphase nuclei) was achieved. Hyperdiploidy and chromosomal heterogeneity without endoduplication in invasive cytotrophoblasts may suggest a selective advantage for invasion and short lifespan during normal placental development.

Publication types

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

MeSH terms

  • Aneuploidy
  • Cell Nucleus
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence / methods
  • Interphase / genetics
  • Placenta*
  • Pregnancy
  • Trophoblasts*

Grants and funding

This work was financially supported by the National Institute of Health in the form of grants (CA-88258, HD-045736 and HD-044313, HD-041425) awarded to JW., This work was also financially supported by the Director, Office of Energy Research, Office of Health and Environmental Research, U.S. Department of Energy, under contract (DE-AC02-05CH11231) awarded to HUW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.