Parental Origin and Phenotype of Triploidy in Spontaneous Abortions: Predominance of Diandry and Association with the Partial Hydatidiform Mole

Abstract

The origin of human triploidy is controversial. Early cytogenetic studies found the majority of cases to be paternal in origin; however, recent molecular analyses have challenged these findings, suggesting that digynic triploidy is the most common source of triploidy. To resolve this dispute, we examined 91 cases of human triploid spontaneous abortions to (1) determine the mechanism of origin of the additional haploid set, and (2) assess the effect of origin on the phenotype of the conceptus. Our results indicate that the majority of cases were diandric in origin because of dispermy, whereas the maternally-derived cases mainly originated through errors in meiosis II. Furthermore, our results indicate a complex relationship between phenotype and parental origin: paternally-derived cases predominate among "typical" spontaneous abortions, whereas maternally-derived cases are associated with either early embryonic demise or with relatively late demise involving a well-formed fetus. As the cytogenetic studies relied on analyses of the former type of material and the molecular studies on the latter sources, the discrepancies between the data sets are explained by differences in ascertainment. In studies correlating the origin of the extra haploid set with histological phenotype, we observed an association between paternal-but not maternal-triploidy and the development of partial hydatidiform moles. However, only a proportion of paternally derived cases developed a partial molar phenotype, indicating that the mere presence of two paternal genomes is not sufficient for molar development.

Cytogenetic analyses of culture failures by comparative genomic hybridisation (CGH)–Re-evaluation of chromosome aberration rates in early spontaneous abortions

“…In practice XYY triploids have rarely been observed, accounting for about 3% of all triploids and were associated with early embryonic demise. 34,35 In our own material we found a relation of 1.5XXX : 1XXY : 1XYY (n=7) in the CGH series and of 1XXX : 1.5XXY : 0.08XYY (n=459) in the cytogenetically analysed abortion material. The observed differences in m=microsatellite analysis, f=FISH, mat=maternal, pat=paternal.…”

Advanced paternal age and reproductive outcome

“…Diandric (paternal) triploids, originate from dispermy, whereas digynic (maternal) triploids originate from errors in meiosis II. 42 However, data are lacking in regard to the effect of paternal age on the incidence of triploidy.…”

Characteristics of hydatidiform moles: analysis of a prospective series with p57 immunohistochemistry and molecular genotyping

“…In contrast, partial hydatidiform moles are characterized by diandric triploidy (two paternal and one maternal chromosome complements), with most arising by dispermy. [36][37][38] Non-molar specimens are usually characterized by biparental diploidy (one paternal and one maternal chromosome complements). Some non-molar specimens are digynic triploid conceptions (two maternal and one paternal chromosome complements) but do not exhibit molar features, 39 with the exception of rare examples having the morphology and immunophenotype (p57-negative) of complete hydatidiform moles occurring in patients with familial recurrent hydatidiform mole associated with mutations in NLRP7 (NALP7) or KHDC3L (C6orf221).…”