Parental origin of triploidy in human fetuses: evidence for genomic imprinting

Abstract

Two distinct phenotypes of triploid fetuses have been previously described and a correlation with parental origin of the triploidy has been suggested. We have studied the parental origin of the extra haploid set of chromosomes in nine triploid fetuses using analysis of DNA polymorphisms at a variety of loci. Maternal origin of the triploidy (digyny) was demonstrated in six fetuses with type II phenotype, paternal origin (diandry) in two cases with type I phenotype, and nonpaternity in one case. The predominance of digynic triploids in our study contrasts with the results reported in previous studies in which, through analysis of cytogenetic polymorphisms, paternal origin was found to account for the majority of triploid conceptuses. This difference may be accounted for by a combination of factors--the different methods of parental assignment used and analysis of a different subset of triploid conceptuses. The correlation between the observed phenotypes and the parental origin of triploidy may represent another example of imprinting in human development.

Polyploid Incidence and Evolution

“…Although most triploids and tetraploids have severe defects and fail to survive to term, livebirths do occasionally occur with infants surviving for up to two years (55,107). Imprinting has been implicated as a possible mechanism causing developmental abnormalities in triploids (32,80), based on the observation that survival is higher for digynic triploids (formed from polyploidization in the egg) than for dispermic triploids (formed from polyploidization in the sperm or, more commonly, fertilization by two sperm). Consistent with what is known about imprinting in mammals, digynic triploids develop at an appropriate rate but display stunted growth, while dispermic triploids are larger than expected based on their developmental stage (80).…”

“…Unreduced sperm, however, appear to play a minor role in polyploidization in animals, perhaps because diploid sperm are rarely successful in competition with reduced sperm (see Reference 3 for an exception). Polyspermy is also known in plants and animals and is, for example, the most common mechanism leading to human triploids (119), which comprise ∼1-3% of conceptions (80). Ramsey & Schemske (99) estimate that autotetraploid plants are formed at a rate on the order of 10 −5 per individual per generation.…”

Parental origin and mechanisms of formation of triploidy: a study of 25 cases

“…[1][2][3] Two distinct phenotypes are known to be associated with triploidy. A minority of foetuses presents with moderate growth retardation, proportionately sized body parts and particularly large placentas with partial hydatidiform mole (type I [4][5][6] ). The second more common phenotype includes a more severe growth retardation.…”

“…The second more common phenotype includes a more severe growth retardation. Typical in such cases is a relative macrocephaly resulting from the uneven development of body parts, with a particular growth retardation of the trunk and limbs (type II [4][5][6] ). Features that are often observed in both groups include syndactylies, usually involving the third and fourth fingers and toes and heart defects.…”

“…[7][8][9] More recent studies, based on the molecular analysis of microsatellite markers, clearly indicate that triploidies of maternal origin are far more frequent than those of paternal origin in foetuses with gestational ages of 10 weeks or more. 5,10 Reasons for the discrepancies could be first of all related to the different methods used for ascertaining the parental origin of the triploidies; indeed, the use of molecular markers as opposed to cytogenetic polymorphisms allows a higher degree of accuracy. A further reason for the apparently contradictory results of different studies could be attributed to a detection bias in favour of cases associated with an abnormal placenta in early gestational ages.…”