Center for Demographic Studies, Duke University, 2117 Campus Drive, Durham, NC 27708, USA e-mail: mgolub{at}cds.duke.edu
Dear Sir,
There are two well-recognized enigmas in the ethnic reproductive pattern: higher hydatidiform mole (HM) incidence and lower dizygotic (DZ) twin rate in some South-East Asian countries in comparison with populations of Europe and the USA (Bortolus et al., 1999). A recent paper by Matsui et al. (2003
) adds new important insights in the understanding of the first puzzle. The authors presented comprehensive data that incidence of HM per 1000 live births in Japan was rather high and constant in the years 1974 to 1990 (2.23.3); however it decreased significantly after 1991. They also found that this trend resulted from a decline of complete HM, while the incidence of partial HM has stayed constant over 16 years.
Partial moles are androgenic triploids, they have always one maternal and two paternal genomes (Genest et al., 2002) and result predominantly from dispermy (McFadden et al., 2002
). Complete moles are the result of diploid androgenesis, they do not have maternal genome and their origin is enigmatic. It is generally assumed that complete HM originates by fertilization of an empty oocyte by a two haploid spermsheterozygous moleor by one sperm with subsequent endoreplicationhomozygous mole (Petignat et al., 2003
). Thus, for an explanation of the striking trend in the rate of complete HM, the authors speculate that Japanese women of reproduction age have lost, over the last decade, the increased risk of ovulating empty oocytes. The influence of some socio/environmental factors is proposed.
In my opinion, this explanation needs some remarks and additions. First, in spite of tens of thousands of direct observations of mature oocytes extracted during IVF procedures there is no convincing evidence for a reservoir of empty oocytes (Golubovsky, 2003). The empty follicle syndrome was described (Zreik et al., 2000
), but no regular findings of empty oocytes were demonstrated. Second, the data reported by the authors contain important indications on the reversed dependence between the rate of complete and partial moles. Indeed, the lowest complete HM incidence in two successive years 1999 and 2000, (0.57 and 0.49) was accompanied by the highest rate of partial HM (1.02 and 1.16). Correspondingly, an opposite trend was observed in the years 1985 and 1989 (Matsui et al., 2003
). Third, it appears that the decline of complete HM in the beginnings of the 1990s was accompanied practically simultaneously by the opposite trenda drastic increase in the rate of DZ twins (Imaizumi and Nonaka, 1997
). All of these facts indicate the causative linkage between three relevant reproduction abnormalities.
I argue that the focus of the explanation needs to be shifted from empty oocytes to the fertilization process itself, namely, to the events associated with the dispermy. A reasonable estimate suggests that overall, 7% of human oocytes are penetrated by more than one sperm (Feng and Gordon, 1996). Three abnormal fertilization scenarios are expected in the cases of dispermy. They are depicted in Figure 1: (i) fusion of all pronuclei and occurrence of diandric triploidy and partial HM; (ii) developmental repression of female MII products, fusion of two male pronuclei resulting in the diploid androgenesis and complete HM and (iii) equal oocyte division with extrusion of large second polar body (small circles in Figure 1) and possible double fertilization of two female MII products resulting in twins. These twins will have two distinct paternal genomes but two similar maternal genomes, differing only due to female crossing-over in MI. They were labelled as the sesquizygotic or SZ twins and it is hard to discriminate them from the usual DZ twins (discussion: Golubovsky, 2002
).
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The South-East Asian and European populations may differ on the distribution of both maternally and paternally dependent genes which, in the case of dispermy, may favour one or another pattern of fertilization. The preferable choice of one definite way will automatically decrease the incidence of another way. If, for instance, the genes favouring the diploid androgenesis have higher a concentration in Japan, it may explain both the increased rate of complete HM and decreased rate of DZ-SZ twins and triploidy (partial mole). Apparently, the choice and implementation of any dispermic fertilization scenario might be modified by socio/environmental factors.
References
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