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

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

Author information

1
1 Department of Oncology, KU Leuven, Leuven, Belgium.
2
2 Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium.
3
3 TRACE (the patient-derived human xenograft platform), Catholic University of Leuven, KU Leuven, Leuven, Belgium.
4
4 Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium.
5
5 Genomics Core, KU Leuven, Leuven, Belgium.
6
6 Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
7
7 Center for Gynecologic Oncology Amsterdam (CGOA), Netherlands Cancer Institute, (NKI), Amsterdam, the Netherlands.

Abstract

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

PMID:
29439620
DOI:
10.1177/1933719118756771
[Indexed for MEDLINE]

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