Discussion
In the studies retrieved in the literature review, oocyte activation, parthenogenesis and UPD were mentioned. This raises the question of whether there are any differences and correlations between oocyte activation, parthenogenesis and UPD.
Oocyte activation is a series of events that converts an MII-arrested oocyte into a fertilized egg ready to begin embryogenesis. In most mammals, oocyte activation is a spatial-temporal regulated process triggered by sperm entry (8).
By activating mouse eggs with experimentally controlled and precisely defined calcium transients, Ducibella et al (9) demonstrated that each of the early events of mammalian oocyte activation is initiated by a different number of calcium transients, while their completion requires a greater number of calcium transients than for their initiation (8). A variety of artificial activating methods is used in human assisted reproduction treatment, including physical, mechanical or chemical stimuli, which provoke one or more calcium rises in the oocyte cytoplasm (8). However, spontaneous oocyte activation may occur under experimental conditions, providing genetic material for PGD diagnostics, as reported by Paffoni et al (10).
Parthenogenesis, a unique form of reproduction, is normally inhibited in mammals and a human embryo with parthenogenetic origin is not considered capable of producing offspring (1). It was reported that parthenogenetic activation took place around the time of fertilization of a sperm missing a sex chromosome, resulting in the generation of the upid(AC)mat 46,XX cell lineage by endoreplication of one blastomere containing a female pronucleus and the 45,X cell lineage by union of male and female pronuclei (9,11).
Artificial activation may also be used to obtain parthenogenetic mammalian embryos that may serve as a model to study biochemical and morphological events. Fresh and aged human oocytes may be activated parthenogenetically using a calcium ionophore. Ethanol was proven to be a poor activating agent. Human parthenotes may complete division to the eight cell stage (11,12). Parthenogenesis may also be induced by exposure of unfertilized oocytes to strontium-containing medium (13). Certain early human pregnancy losses may involve oocytes that have been parthenogenetically activated spontaneously (2,14).
UPD refers to the situation in which both homologues of a chromosomal region/segment have originated from only one parent. UPD and mosaic aneuploidy arise from mitotic or meiotic events (15). As a consequence of UPD, or deficiency of part of a chromosome, there are two types of developmental risk: Aberrant dosage of genes regulated by genomic imprinting and homozygosity of a recessive mutation (16). This may involve the entire chromosome or only a small segment. Uniparental disomy in the human blastocyst is exceedingly rare (17).
UPD almost always arises in connection with a numerical or structural chromosomal aberration. UPD cases in which the causative cytogenetic event is still present, even if only in the mosaic state, provide deep insight into the abilities of gametes or embryonic cells to repair chromosomal imbalances and/or rearrangements (18).
In conclusion, there are certain correlations between oocyte activation, parthenogenesis and UPD, but the following are the differences, which are well established: The incidence of UPD of any chromosome is estimated to account for ~1:3,500 live births. For certain chromosomes, UPD does not exert any adverse effect on any individual. However, for other chromosomes, it may result in abnormalities due to aberrant genomic imprinting (16). In humans, parthenogenesis always leads to teratoma and never to a viable individual (1).
In the present study, the first cycle used was IVF short-time fertilization. After the removal of the cumulus cells, two early cleavage embryos were discovered. ICSI was performed in the second cycle and prior to injection, two 6-cell embryos were discovered and tested. Although recurrent spontaneous parthenogenesis was observed, this did not influence the other MII oocyte fertilization and the achievement of pregnancy. It was hypothesized that the bilateral salpingectomy resulted in recurrent spontaneous oocyte activation. This is a similar case to that reported by Combelles et al (2), where the patient had two cycles of spontaneous oocyte activation and underwent left oophorectomy due to an ovarian teratoma.
In humans, parthenogenesis never results in a viable individual. In the present study, the parthenogenetic embryos were observed for three days and exhibited no changes. Although there were two parthenogenetic embryos, this did not influence the other oocyte fertilization and the resulting pregnancy. In the present case, the healthy baby that was born originated from the other normal oocyte.
The present results indicated that the first 6-cell embryo was not able to be observed in the amplification concentrate. The reason was probably that not every blastomere contains genomes. As with the previously reported case, only one of eight blastomeres contained genomes, indicating that the oocyte underwent cleavage without genome replication, or another probability was that what was assumed to be the 7 blastomeres were actually embryo fragments rather than blastomeres (1).
In the present study, the SNP and CNV results for the second 6-cell embryo revealed a genotype of 39,XX,+1,+1,+1,+1,+6q,+6q,+6q,-7p(x1),-10(x1),-13(x0),-15(x0),-17(x1),-18(x1),-19(x1),-20(x1). Only those chromosomes with the presence of one copy exhibited a signal pattern similar to that of a UPD and other chromosomes rather appeared to have a trisomy or tetrasomy copy. The reason may be due to amplification concentration, or other unknown aspects. The mechanisms of the formation of the UPD included trisomy rescue, with and without concomitant trisomy, monosomy rescue and mitotic formation of a mosaic segmental UPD (15). UPD was also identified with one cell line having complete maternal UPD consistent with a parthenogenetic origin (14). Chromosomal segregation was analyzed, revealing a highly probable UPD as the reason for parent/child allele mismatches (19). This indicates that massively imbalanced embryos were identified, as new single-cell genomic methodologies have further pinpointed the existence of mixoploidy in cleavage-stage embryos (20).
Although repeated spontaneous parthenogenesis appeared in the patient of the present study, other oocytes were able to be fertilized normally and the patient became pregnant. The clinical value of the case report was that it demonstrated that pregnancy outcomes were not influenced by the fact that parthenogenesis was observed in part of the oocytes. As with the case reported by Oliveira et al (3), although there was a parthenogenetic origin of the ovarian teratoma, there were eight normally fertilized embryos, three of which were transferred, resulting in a normal single pregnancy and the birth of a healthy baby.
In conclusion, in the present study, a massively imbalanced parthenogenesis embryo was detected, which may occur in patients from various regions, who always have a history of either recurrent miscarriages or bilateral tubal obstruction with or without ovarian/fallopian tube surgery.