Tetraploidy in hydatidiform moles

Abstract

study question: How does tetraploidy develop in hydatidiform moles (HMs), and what is the frequency of the different origins? summary answer: Most molar pregnancies with tetraploid cells appear to be produced by somatic endoreduplications, while a minority originate from a tetraploid zygote. The frequency of zygotic tetraploidy was estimated to be 0.7%.what is known already: The parental origin of the genome in tetraploid HMs has only been evaluated in a few cases, most showing three genome sets from the father (PPPM). Estimates of the proportion of HMs that are tetraploid vary between 2 and 28%. study design, size, duration: From 1986 to 2010, unfixed samples of clinically suspected molar pregnancies were forwarded to the Danish Mole Project. For this cohort study 442 samples fulfilled the following criteria for inclusion: macroscopic appearance of HM and ≥10 vesicular chorionic villi with a diameter of ≥1 mm.participants/materials, setting, methods: Of 403 karyotyped samples, 21 cases disclosed ≥2 tetraploid metaphases.The 21 cases were scrutinized by karyotyping, flow cytometry (FC) and DNA-marker analysis.main results and the role of chance: Among 20 HMs, 3 showed the genotype PPPM: one with the sex chromosomes XXYY and two with XXXY, indicating that they originated in tetraploid zygotes. In 14 androgenetic, one likely androgenetic and two mosaics, the tetraploid cells likely developed by endoreduplications of diploid cells. One case did not fulfil the histopathological criteria for HM.limitations, reasons for caution: As an inclusion criterion was the macroscopic observation of vesicular chorionic villi, some non-molar hydropic placentas may have been included and some early moles may have been excluded.wider implications of the findings: In future, studies to determine that an HM is tetraploid and discriminate cases of mosaicism and to deduce the origin of the tetraploidy must use the techniques of karyotyping, DNA-marker analysis and FC in combination. study funding/competing interest(s): No external funding was sought to support this study. None of the authors has any conflict of interest to declare.

A 92,XXXY Miscarriage Consecutive to a Digynic Triploid Pregnancy

“…The results of the DNA marker analysis corroborated this statement, since in several loci this pregnancy showed 2 different paternal alleles or 2 different maternal alleles or both. To our knowledge such karyotype has only been reported in 6 previous cases, 5 of them associated with partial hydatidiform moles, with a PPPM genotype (3 paternal (P) and 1 maternal (M) alleles) [Surti et al, 1986;Murphy et al, 2012;Sundvall et al, 2013]. The case of Baumer et al [2003] is similar to ours, with a PPMM genotype found in a spontaneously aborted embryo.…”

“…The finding of a complete tetraploidy in native trophoblast cells, evidenced by the CVS short-term culture, might be indicative of a 'zygotic tetraploidy' where all cells are tetraploid and derived from a tetraploid conceptus [Sundvall et al, 2013]. However, in viable pregnancies, complete tetraploidy in a trophoblast is not an infrequent finding and is usually confined to this tissue.…”

Mosaicism in Preimplantation Human Embryos: When Chromosomal Abnormalities Are the Norm

“…This leads to DNA replication without cell division, producing a tetraploid cell. Mosaic tetraploidy is observed in <1% of molar pregnancies [39], but may be more frequent at earlier embryonic stages. Indeed, some studies have suggested tetraploidy to be a normal feature of blastocyst-stage embryos [19].…”

Cell-free DNA in pregnancy with choriocarcinoma and coexistent live fetus

“…However, polyploid molar pregnancies generally show heterozygosity for paternal alleles. [12,13] Although we only had few informative loci, we did not observe heterozygosity for paternal markers making polyploidy unlikely. Increasing the number of loci analyzed could increase the validity of this conclusion.…”