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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2018

Erschienen:

2018

Enthalten in:

Zur Gesamtaufnahme - volume:25

Enthalten in:

Reproductive sciences (Thousand Oaks, Calif.) - 25(2018), 12 vom: 15. Dez., Seite 1637-1648

Sprache:

Englisch

Beteiligte Personen:

Verheecke, Magali [VerfasserIn]
Hermans, Els [VerfasserIn]
Tuyaerts, Sandra [VerfasserIn]
Souche, Erika [VerfasserIn]
Van Bree, Rita [VerfasserIn]
Verbist, Godelieve [VerfasserIn]
Everaert, Tina [VerfasserIn]
Cortès-Calabuig, Alvaro [VerfasserIn]
Van Houdt, Jeroen [VerfasserIn]
Van Calsteren, Kristel [VerfasserIn]
Amant, Frederic [VerfasserIn]

Links:

Volltext

Themen:

4G7DS2Q64Y
Chorionic Gonadotropin
Drug effects
Human xenograft model
Journal Article
Mice
Placenta
Progesterone
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 23.04.2019

Date Revised 23.04.2019

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1177/1933719118756771

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM280984790