Acute Drug Effects on the Human Placental Tissue: The Development of a Placental Murine Xenograft Model

Reprod Sci. 2018 Dec;25(12):1637-1648. doi: 10.1177/1933719118756771. Epub 2018 Feb 13.


Objective: A pilot study was conducted to establish a human placental xenograft, which could serve as a model to evaluate the effect of toxic exposures during pregnancy.

Study design: The protocol consisted of engraftment of third-trimester human placental tissue in immunocompromised mice, after induction of a pseudo-pregnancy state by ovariectomy and progesterone supplementation. To validate the model, the placental tissue before and after engraftment was examined by immunohistochemistry, fluorescence-activated cell sorting (FACS), single-nucleotide polymorphism (SNP) genotyping, and whole transcriptome sequencing (WTSS). The human chorion gonadotropin (hCG) production in serum and urine was examined by enzyme-linked immunosorbent assay.

Results: Microscopic evaluation of the placental tissue before and after engraftment revealed a stable morphology and preserved histological structure of the human tissue. Viable trophoblast was present after engraftment and remained stable over time. Vascularization and hormonal secretion (hCG) were present till 3 weeks after engraftment. Thirty-one SNPs were equally present, and there was a stable expression level for 56 451 genes evaluated by whole transcriptome sequencing.

Conclusion: Although this human placental xenograft model cannot copy the unique uterine environment in which the placenta develops and interacts between the mother and the fetus, it could be a suitable tool to evaluate the acute impact and adaptive processes of the placental tissue to environmental changes.

Keywords: drug effects; human xenograft model; mice; placenta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chorionic Gonadotropin / metabolism
  • Female
  • Heterografts*
  • Humans
  • Mice
  • Placenta / metabolism*
  • Polymorphism, Single Nucleotide*
  • Pregnancy
  • Progesterone / metabolism
  • Pseudopregnancy
  • Transcriptome*


  • Chorionic Gonadotropin
  • Progesterone