TY - JOUR
T1 - Acute Drug Effects on the Human Placental Tissue: The Development of a Placental Murine Xenograft Model
AU - Verheecke, Magali
AU - Hermans, Els
AU - Tuyaerts, Sandra
AU - Souche, Erika
AU - van Bree, Rita
AU - Verbist, Godelieve
AU - Everaert, Tina
AU - van Houdt, Jeroen
AU - van Calsteren, Kristel
AU - Amant, Frederic
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85042560478&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29439620
U2 - https://doi.org/10.1177/1933719118756771
DO - https://doi.org/10.1177/1933719118756771
M3 - Article
C2 - 29439620
SN - 1933-7191
VL - 25
SP - 1637
EP - 1648
JO - Reproductive sciences (Thousand Oaks, Calif.)
JF - Reproductive sciences (Thousand Oaks, Calif.)
IS - 12
ER -