TY - JOUR
T1 - Endocervical trophoblast for interrogating the fetal genome and assessing pregnancy health at five weeks
AU - Kadam, L.
AU - Jain, Chandni
AU - Kohan-Ghadr, Hamid Reza
AU - Krawetz, Stephen A.
AU - Drewlo, Sascha
AU - Armant, D. Randall
N1 - Funding Information:
Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute on Minority Health and Health Disparities of the National Institutes of Health under Awards Number R43HD092205, R43HD094405 and R43HD097904. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Support was also provided by the W.K. Kellogg Foundation (USA) and PerkinElmer Health Sciences, Inc, Waltham, MA, USA.
Funding Information:
Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute on Minority Health and Health Disparities of the National Institutes of Health under Awards Number R43HD092205 , R43HD094405 and R43HD097904 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health . Support was also provided by the W.K. Kellogg Foundation (USA) and PerkinElmer Health Sciences, Inc, Waltham, MA, USA .
Publisher Copyright:
© 2019 Elsevier Masson SAS
PY - 2019/8
Y1 - 2019/8
N2 - Prenatal testing for fetal genetic traits and risk of obstetrical complications is essential for maternal-fetal healthcare. The migration of extravillous trophoblast (EVT) cells from the placenta into the reproductive tract and accumulation in the cervix offers an exciting avenue for prenatal testing and monitoring placental function. These cells are obtained with a cervical cytobrush, a routine relatively safe clinical procedure during pregnancy, according to published studies and our own observations. Trophoblast retrieval and isolation from the cervix (TRIC) obtains hundreds of fetal cells with >90% purity as early as five weeks of gestation. TRIC can provide DNA for fetal genotyping by targeted next-generation sequencing with single-nucleotide resolution. Previously, we found that known protein biomarkers are dysregulated in EVT cells obtained by TRIC in the first trimester from women who miscarry or later develop intrauterine growth restriction or preeclampsia. We have now optimized methods to stabilize RNA during TRIC for subsequent isolation and analysis of trophoblast gene expression. Here, we report transcriptomics analysis demonstrating that the expression profile of TRIC-isolated trophoblast cells was distinct from that of maternal cervical cells and included genes associated with the EVT phenotype and invasion. Because EVT cells are responsible for remodeling the maternal arteries and their failure is associated with pregnancy disorders, their molecular profiles could reflect maternal risk, as well as mechanisms underlying these disorders. The use of TRIC to analyze EVT genomes, transcriptomes and proteomes during ongoing pregnancies could provide new tools for anticipating and managing both fetal genetic and maternal obstetric disorders.
AB - Prenatal testing for fetal genetic traits and risk of obstetrical complications is essential for maternal-fetal healthcare. The migration of extravillous trophoblast (EVT) cells from the placenta into the reproductive tract and accumulation in the cervix offers an exciting avenue for prenatal testing and monitoring placental function. These cells are obtained with a cervical cytobrush, a routine relatively safe clinical procedure during pregnancy, according to published studies and our own observations. Trophoblast retrieval and isolation from the cervix (TRIC) obtains hundreds of fetal cells with >90% purity as early as five weeks of gestation. TRIC can provide DNA for fetal genotyping by targeted next-generation sequencing with single-nucleotide resolution. Previously, we found that known protein biomarkers are dysregulated in EVT cells obtained by TRIC in the first trimester from women who miscarry or later develop intrauterine growth restriction or preeclampsia. We have now optimized methods to stabilize RNA during TRIC for subsequent isolation and analysis of trophoblast gene expression. Here, we report transcriptomics analysis demonstrating that the expression profile of TRIC-isolated trophoblast cells was distinct from that of maternal cervical cells and included genes associated with the EVT phenotype and invasion. Because EVT cells are responsible for remodeling the maternal arteries and their failure is associated with pregnancy disorders, their molecular profiles could reflect maternal risk, as well as mechanisms underlying these disorders. The use of TRIC to analyze EVT genomes, transcriptomes and proteomes during ongoing pregnancies could provide new tools for anticipating and managing both fetal genetic and maternal obstetric disorders.
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U2 - 10.1016/j.ejmg.2019.103690
DO - 10.1016/j.ejmg.2019.103690
M3 - Article
C2 - 31226440
AN - SCOPUS:85067894649
SN - 1769-7212
VL - 62
JO - European Journal of Medical Genetics
JF - European Journal of Medical Genetics
IS - 8
M1 - 103690
ER -