Trophoblast Retrieval and Isolation From the Cervix for Noninvasive, First Trimester, Fetal Gender Determination in a Carrier of Congenital Adrenal Hyperplasia

Bolnick, Alan; Fritz, Rani; Jain, Chandni; Kadam, Leena; Bolnick, Jay M.; Kilburn, Brian A.; Singh, Manvinder; Diamond, Michael P.; Drewlo, Sascha; Armant, D. Randall

doi:10.1177/1933719116632922

Cited by 14 publications

(7 citation statements)

References 36 publications

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“…Recently, HLA-G-positive extravillous trophoblasts have been retrieved from the endocervical canal and used for non-invasive prenatal testing (Bolnick et al 2016a , b ). These authors have shown that it is possible to collect extravillous trophoblasts from the cervix with a brush and separate trophoblasts from maternal cells for downstream analysis of fetal DNA, RNA, proteins and others (Drewlo and Armant 2017 ).…”

Section: Migratory Routes Of Extravillous Trophoblast In Normal Pregnmentioning

confidence: 99%

Human trophoblast invasion: new and unexpected routes and functions

Moser

Windsperger

Pollheimer

et al. 2018

Histochem Cell Biol

135

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Until recently, trophoblast invasion during human placentation was characterized by and restricted to invasion into uterine connective tissues and the uterine spiral arteries. The latter was explained to connect the arteries to the intervillous space of the placenta and to guarantee the blood supply of the mother to the placenta. Today, this picture has dramatically changed. Invasion of endoglandular trophoblast into uterine glands, already starting at the time of implantation, enables histiotrophic nutrition of the embryo prior to perfusion of the placenta with maternal blood. This is followed by invasion of endovenous trophoblasts into uterine veins to guarantee the drainage of fluids from the placenta back into the maternal circulation throughout pregnancy. In addition, invasion of endolymphatic trophoblasts into the lymph vessels of the uterus has been described. Only then, invasion of endoarterial trophoblasts into spiral arteries takes place, enabling hemotrophic nutrition of the fetus starting with the second trimester of pregnancy. This new knowledge paves the way to identify changes that may occur in pathological pregnancies, from tubal pregnancies to recurrent spontaneous abortions.

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Section: Migratory Routes Of Extravillous Trophoblast In Normal Pregnmentioning

confidence: 99%

Human trophoblast invasion: new and unexpected routes and functions

Moser

Windsperger

Pollheimer

et al. 2018

Histochem Cell Biol

135

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“…TRIC has been used successfully with FISH and PCR to unequivocally determine fetal sex ( Bolnick et al , 2014 , 2016a ). DNA fingerprinting by targeted next-generation sequencing of STRs and SNPs has now been successfully conducted with EVT cells obtained by TRIC ( Jain et al , 2016 ).…”

Section: Utility Of Tric For Placental Researchmentioning

confidence: 99%

Trophoblast retrieval and isolation from the cervix: origins of cervical trophoblasts and their potential value for risk assessment of ongoing pregnancies

Moser

Drewlo

Huppertz

et al. 2018

Human Reproduction Update

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BACKGROUNDEarly during human development, the trophoblast lineage differentiates to commence placentation. Where the placenta contacts the uterine decidua, extravillous trophoblast (EVT) cells differentiate and invade maternal tissues. EVT cells, identified by expression of HLA-G, invade into uterine blood vessels (endovascular EVT), as well as glands (endoglandular EVT), and open such luminal structures towards the intervillous space of the placenta. Endoglandular invasion diverts the contents of uterine glands to the intervillous space, while glands near the margin of the placenta that also contain endoglandular EVT cells open into the reproductive tract. Cells of the trophoblast lineage have thus been recovered from the uterine cavity and endocervical canal. An emerging non-invasive technology [trophoblast retrieval and isolation from the cervix (TRIC)] isolates and examines EVT cells residing in the cervix to explore their origin, biology and relationship to pregnancy and fetal status.OBJECTIVE AND RATIONALEThis review explores the origins and possible uses of trophoblast cells obtained during ongoing pregnancies (weeks 5–20) by TRIC. We hypothesize that endoglandular EVT cells at the margins of the expanding placenta enter the uterine cavity and are carried together with uterine secretion products to the cervix where they can be retrieved from a Papanicolaou (Pap) smear. The advantages of TRIC for investigation of human placentation and prenatal testing will be considered. Evidence from the literature, and from archived in utero placental histological sections, is presented to support these hypotheses.SEARCH METHODSWe used 52 out of 80 publications that appeared between 1966 and 2017 and were found by searching the PubMed and Google Scholar databases. The studies described trophoblast invasion of uterine vessels and glands, as well as trophoblast cells residing in the reproductive tract. This was supplemented with literature on human placental health and disease.OUTCOMESThe literature describes a variety of invasive routes taken by EVT cells at the fetal–maternal interface that could displace them into the reproductive tract. Since the 1970s, investigators have attempted to recover trophoblast cells from the uterus or cervix for prenatal diagnostics. Trophoblast cells from Pap smears obtained at 5–20 weeks of gestation have been purified (>95% β-hCG positive) by immunomagnetic isolation with nanoparticles linked to anti-HLA-G (TRIC). The isolated cells contain the fetal genome, and have an EVT-like expression profile. Similar EVT-like cells appear in the lumen of uterine glands and can be observed entering the uterine cavity along the margins of the placenta, suggesting that they are the primary source of cervical trophoblast cells. Cells isolated by TRIC can be used to accurately genotype the embryo/fetus by targeted next-generation sequencing. Biomarker protein expression quantified in cervical trophoblast cells after TRIC correlates with subsequent pregnancy loss, pre-eclampsia and fetal growth re...

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“…Most recently, trophoblast cells were identified via endocervical cells obtained via standard speculum exam with cytobrush and are being investigated as a possible additional option for noninvasive prenatal diagnosis. 25,26…”

Section: What New Tests Are Coming and What Are The Considerations Fomentioning

confidence: 99%

Introducing new and emerging genetic tests into prenatal care

Vora

Wapner

2018

Seminars in Perinatology

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Given the rapid advances in genomics, translating new genomic tests effectively into prenatal clinical practice remains challenging. We discuss emerging genetic tests, considerations for their use, how tests should ideally be validated prior to use in clinical practice, and the role of the Federal Drug Administration, Clinical Laboratory Improvement Amendments (CLIA) laboratories, commercial laboratories, insurers, and professional societies such as the American College of Obstetricians and Gynecologists (ACOG), and the Society for Maternal-Fetal Medicine (SMFM) in the introduction of new prenatal genetic tests. After the introduction of new tests into the prenatal clinic, it is critical to utilize shared databases with measured outcomes to improve clinical care as well as to advance science.

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Trophoblast Retrieval and Isolation From the Cervix for Noninvasive, First Trimester, Fetal Gender Determination in a Carrier of Congenital Adrenal Hyperplasia

Cited by 14 publications

References 36 publications

Human trophoblast invasion: new and unexpected routes and functions

Human trophoblast invasion: new and unexpected routes and functions

Trophoblast retrieval and isolation from the cervix: origins of cervical trophoblasts and their potential value for risk assessment of ongoing pregnancies

Introducing new and emerging genetic tests into prenatal care

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