Abstract
In 1996, Tesarik reported the first successful case of ROSI and many successful cases were reported around the world, however very few cases of deliveries were reported. Many doctors began to become doubtful about the usefulness of ROSI and it almost disappeared from the field of ART. Based on recent advances on ROSI research, I think it is now necessary to reconsider the usefulness of ROSI. There are three issues concerning the extremely low success rate of ROSI. The first is the cytodifferentiation of round spermatid from other round cells. The most difficult cytological differentiation is between spermatogonia and round spermatid. The second is insufficient oocyte activation. Finally, ROSI improvement is being prevented by epigenetic errors. The big difference in ROSI and ICSI is caused by different nuclear proteins. We are now experimenting how to solve those epigenetic errors using histone deacetylase inhibitor. The first two problems have almost been solved. The only problem we are yet to overcome is the epigenetic abnormality. The big difference between ROSI and ICSI is the different type of nuclear protein. In a round spermatid is histone and in a spermatozoon is protamine. Normal transformation of nucleosomes into nucleoprotamine is generated in normal spermatogenesis. The characteristics of nuclei of RS are ①incomplete histone-protein transition (incomplete chromatin reprograming), ②active DNA demethylation, then these epigenetic errors affect gene expression. We are now conducting some experiments to solve these problems. The experiment involves the correction of abnormal gene expression by using histone deacetylase inhibitor. However, this method is not yet allowed clinically. I believe these procedures will be allowed for clinical application after accumulation of positive evidence by researchers.
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