Somatic Genomic Variations in Extra-Embryonic Tissues

Abstract

In the mature chorion, one of the membranes that exist during pregnancy between the developing fetus and mother, human placental cells form highly specialized tissues composed of mesenchyme and floating or anchoring villi. Using fluorescence in situ hybridization, we found that human invasive cytotrophoblasts isolated from anchoring villi or the uterine wall had gained individual chromosomes; however, chromosome losses were detected infrequently. With chromosomes gained in what appeared to be a chromosome-specific manner, more than half of the invasive cytotrophoblasts in normal pregnancies were found to be hyperdiploid. Interestingly, the rates of hyperdiploid cells depended not only on gestational age, but were strongly associated with the extraembryonic compartment at the fetal-maternal interface from which they were isolated. Since hyperdiploid cells showed drastically reduced DNA replication as measured by bromodeoxyuridine incorporation, we conclude that aneuploidy is a part of the normal process of placentation potentially limiting the proliferative capabilities of invasive cytotrophoblasts. Thus, under the special circumstances of human reproduction, somatic genomic variations may exert a beneficial, anti-neoplastic effect on the organism.

Single Cell Genomics of the Brain: Focus on Neuronal Diversity and Neuropsychiatric Diseases

“…Nonetheless, considering the devastating effect of aneuploidy on cellular phenotypes [ 3 , 7 , 12 , 81 , 82 ], one can suggest that a number of mosaic embryos are likely to be spontaneously aborted because of high incidence of chromosomal mosaicism in human miscarriages [ 82 , 83 ]. A possibility of a decrease in the rates can be produced through aneuploid cells to become extraembryonic in as much as human placenta is hallmarked by aneuploidization during gestation [ 76 , 84 ]. It is further supported by the observations of confined placental mosaicism suggesting the phenomenon to occur relatively frequently as to the direct studies [ 85 ] and as to tracing back of mosaicism in liveborns by molecular cytogenetic analysis of uniparental disomy [ 86 ].…”

Bioinformatic Tools Identify Chromosome-Specific DNA Probes and Facilitate Risk Assessment by Detecting Aneusomies in Extra-embryonic Tissues

“…We decided to perform investigations on uncultured interphase cells using fluorescence in situ hybridization (FISH), since cell viability or proliferation are minor concerns when using FISH [ 1 - 5 ]. Probes for our initial studies of aneuploidy in extra-embryonic tissues were obtained from a commercial source (Abbott, Des Moines, IL) [ 6 , 7 ]. Probe sets were comprised of three to four chromosome enumerator probes (CEPs) targeting chromosome types, X, Y, 16 or 18, or locus-specific probes (LSPs) for chromosome 13 or 21 [ 7 ].…”

“…Probes for our initial studies of aneuploidy in extra-embryonic tissues were obtained from a commercial source (Abbott, Des Moines, IL) [ 6 , 7 ]. Probe sets were comprised of three to four chromosome enumerator probes (CEPs) targeting chromosome types, X, Y, 16 or 18, or locus-specific probes (LSPs) for chromosome 13 or 21 [ 7 ]. Studying the chromosomal make-up of cells in different compartments of anchoring villi and the uterine wall also referred to as ‘basal plate’, we found that the karyotypes of these extra-embryonic cells were mostly unrelated to the karyotype of the fetus [ 5 , 7 , 8 ].…”

“…Probe sets were comprised of three to four chromosome enumerator probes (CEPs) targeting chromosome types, X, Y, 16 or 18, or locus-specific probes (LSPs) for chromosome 13 or 21 [ 7 ]. Studying the chromosomal make-up of cells in different compartments of anchoring villi and the uterine wall also referred to as ‘basal plate’, we found that the karyotypes of these extra-embryonic cells were mostly unrelated to the karyotype of the fetus [ 5 , 7 , 8 ]. The most common abnormality we have observed was a gestational age-related gain of chromosomes affecting invading cytotrophoblasts (iCTB’s) [ 7 ].…”

Bioinformatics Tools Allow Targeted Selection of Chromosome Enumeration Probes and Aneuploidy Detection

“…For example, in prenatal/pre-implantation genetic analyses (Cassel et al 1997; Bucksch et al 2012) or stem cell research (Hessel et al 1996; Weier et al 2004; Kwon et al 2010), as a means of controlling the rate of fetal cellular proliferation at the fetal-maternal interface (Weier et al 2005; Weier et al 2010) or determining the fate of regenerating tissues, assessment of aneuploidy may be of substantial importance (Pujol et al 2003; Kodama et al 2009; Kwon et al 2010). However, whereas other methods, such as chorionic villus sampling (CVS) with in vitro culture-based karyotyping of metaphase spreads, have presented difficulties in detecting aneusomies because abnormal cells can arise in any portion of the placenta or fetal-maternal interphase but might not be proliferating (Weier et al 2005), we rely on chromosome-specific FISH assay to accurately determine the cellular chromosome complements in interphase cells.…”