A new breakthrough led by scientists at Salk Institute for Biological Studies and the OHSU could someday benefit families struggling with a genetic predisposition for debilitating mitochondrial diseases or infertility.
Researchers discovered that it is possible to use genetic material that normally goes to waste to regenerate oocytes – the cellular beginning of an embryo, or human eggs. The DNA used in the study comes from small cells called polar bodies. These polar bodies contain the same genetic material as in a woman’s egg nucleus and from the eggs.
Polar bodies have until now never been seen as being potentially useful for generating functional human eggs that can be used in fertility treatments. During this research, scientists managed to transplant a polar body from a woman’s developing oocyte into the cytoplasm of a donor oocyte that had been stripped of its nucleus.
Although it will be years before the technique can progress to clinical trials, the progress could eventually be significant for women of an advanced maternal age. A recent survey in the United States showed that the average age of first-time mothers increased to 25.0 years in 2006 from 21.4 years in 1970.
Shoukhrat Mitalipov, Ph.D. and director of the OHSU Center for Embryonic Cell and Gene Therapy is a co- senior author of the paper. He explained that as women get older, fertility declines. The results of the study show a method that will potentially double the number of eggs that can be obtained from one session of in vitro fertilization.
Joseph Ecker, Ph.D., Salk professor and director of the Genomic Analysis Laboratory and co-senior author, noted that from the point of view of epigenomic profiles, it was only possible to examine a limited number of lines. In spite of this, the quality of polar body-derived embryonic cells is promising.
By using rescued polar bodies that would normally simply bud off the developing oocyte, researchers managed to form additional oocytes genetically related to the mother through nuclear transfer. The new oocytes formed in this way developed into viable embryos when fertilized with sperm. The new embryos were not implanted to carry out an actual pregnancy.
Hong Ma, M.D., Ph.D., with OHSU’s Center for Embryonic Cell and Gene Therapy and co-first author hopes that the number of patient eggs available for in vitro fertilization can be doubled by recycling polar bodies that normally disintegrate and disappear during egg development.
Ryan O’Neil, co-first author and Salk researcher notes that this first investigation into the viability of human polar bodies reveals a new source of genetic material that was previously discarded.
Apart from potentially benefitting women of advanced maternal age, the technique may also present an opportunity to help women that have mutations in their mitochondria. Mitochondria are tiny powerhouses inside nearly every cell of the body and mutations in these can lead to debilitating forms of disease in children.
Mitalipov thinks that this new technique will maximize the chances of families having a child free of genetic mutations through in vitro fertilization. Mitalipov has been involved in infertility treatments for years and has previously developed a mitochondrial replacement therapy that involved the implantation of patient’s egg nucleus – or spindle – into a healthy donated egg that had been stripped of its original nucleus. This spindle-transfer technique was successfully demonstrated with the healthy offspring of rhesus macaque monkeys.