Triploidy

Definition

Nuclei of most human cells contain two sets of haploid chromosomes, one inherited from each parent, which join to create 23 pairs of chromosomes. Each normal diploid cell has a 2 n constitution: 46 chromosomes (22 pairs of autosomes and one pair of sex chromosomes). This normal state is termed euploidy . The presence of additional haploid sets of chromosomes is referred to as polyploidy. For instance, triploidy describes the presence of a complete extra haploid set of chromosomes (the cell complement is 3 n , i.e., 69 chromosomes), and tetraploidy describes two extra haploid sets of chromosomes (4 n , i.e., 92 chromosomes).

Prevalence and Epidemiology

Triploidy, which is lethal, occurs in 1% to 3% of all clinically recognized conceptions. Polyploid conceptions, which account for about one-quarter of spontaneous abortions, typically demise early in development. Triploidy is the third most common cytogenetic abnormality identified at spontaneous abortion (15%), preceded by monosomy X (20%) and trisomies (60%). Its prevalence at 16 to 20 weeks is 20 : 10,000, and it is rarely reported in live births (1 : 10,000). There are no reported survivors beyond 10 months, although sporadic reports describe mosaic individuals living into their 20s. Triploidy is sporadic, and its rate, in contrast to trisomy, does not increase with advancing maternal age.

Etiology and Pathophysiology

The joining of one haploid spermatozoon and one haploid oocyte produces a normal diploid cell count of 46 chromosomes. Proper meiosis (gamete formation) ensures that gametes are haploid in number before fusion. If there is an error in meiosis I or meiosis II, the gamete may remain in the diploid state. Triploidy can arise from (1) the fertilization of one egg by two spermatozoa, a condition referred to as dispermy; (2) fertilization of one oocyte by a diploid sperm, referred to as diandry; or (3) fertilization of a diploid oocyte by one sperm, referred to as digyny . When a normal haploid oocyte is fertilized by two haploid sperm or a diploid sperm, the karyotype result can be XXX, XXY, or XYY. This is type I triploidy and is paternally derived (two sets of the haploid chromosomes are paternal in origin). Type II triploidy is maternally derived and results from the fertilization of a diploid oocyte by a haploid sperm, and the karyotype result can be XXX or XXY (two sets of the haploid chromosomes are maternal in origin). The distribution of karyotypes seen in triploid conceptuses is 69,XXY (60%), 69,XXX (37%), and 69,XYY (3%).

The origin of human triploidy is controversial. Initial studies of parental origin of triploidy showed that most cases of triploid conceptuses were of paternal origin, with dispermy being the most common cause. Redline et al. examined 1054 karyotyped spontaneous abortions before 20 weeks' gestation. Triploidy was detected in 64 of 832 successfully karyotyped specimens. Polymerase chain reaction analysis for parent of origin of the extra haploid chromosomal set was successful in 59 of 64 triploids analyzed. Paternal origin was confirmed in 39 cases (66%). However, later studies reported that most cases of triploidy were of maternal origin. The difference between these studies might be explained by the gestational age included in the analysis. Early studies of triploid conceptuses included specimens from a wide range of gestational ages, usually without correlation with developmental stage of the embryo or fetus. When analysis is divided into embryonic diagnosis (<10 weeks' gestation) versus fetal diagnosis (>10 weeks' gestation), maternal origin appears to be more common in pregnancies that persist beyond the embryonic period.