How to ¨Make an Egg¨

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Hans van der Slikke, MD: "It's the 23rd of October 2001, we're at the ASRM in Orlando, and next to me is Dr. Palermo. Welcome, Dr. Palermo. You're an obstetrician-gynecologist who trained in Italy and at the moment you're working at Cornell University. You presented about, let's say: ¨making an egg¨, this afternoon, could you tell us what the main goal of your research is?"

Gianpiero D. Palermo, MD: "The aim of our work is to try to help women in advanced reproductive age, who no longer produce any eggs to have their own baby. Although this technique is still experimental so it's not yet offered to patients, at least conceptually it is the only way to cure, to treat age related infertility. As we know women over thirty-five have a decreased ability to reproduce because of a higher incidence of chromosomal abnormalities - so called aneuploidy. By the age of forty this can get all the way up to 40%-50% so the only way to solve the problem is to transplant a nucleus of an older egg into a younger cytoblast. This would allow the correction of the problem but in this case the patient would still need to have some eggs. What we are trying to do is to kind of manufacture oocyte eggs by taking a somatic cell."

Hans van der Slikke, MD: "What kind of cell do you take then in this case?"

Gianpiero D. Palermo, MD: "We have used an endometrial cell and some of our colleagues involved in another study have used a fibroblast cell which can also be used. We have also used common cell and this is just for a practical reason - it's just easy to retrieve but in theory any cell of the body could be used as long as it has a normal chromosomal number and is healthy."

Hans van der Slikke, MD: "You take this cell and then what do you do?"

Gianpiero D. Palermo, MD: "The cell is injected into an egg which has been enucleated where the genome of this donor is removed, and once it's injected into the cytoblast the egg is activated. We try to wake up the egg by an electrical or chemical stimulus, it depends. Once the egg is activated it's able to segregate chromosomes so making the somatic cell a so-called haploid. That means instead of the forty-six chromosomes typical of the normal cell of a human body it's twenty-three and like a germ cell beginning a gamete so that's our goal at the present time. We've done this experiment in a mouse, and we have also used some spare human eggs of a patient undergoing the ICSI procedure."

Hans van der Slikke, MD: "This is the first step to have this egg, and then the question is could you fertilize this egg? Have you done some experiments with it?"

Gianpiero D. Palermo, MD: "Yes, we have inseminated it. Actually, if you look into this technique it's very similar to cloning, technically, but the major difference with cloning is we want to insure the biparental contribution to the offspring. So in this case the mother would contribute with her own genome and we still would let the sperm contribute for the paternal genome. We have haploidized this egg and inseminated it with sperm and we have been able to obtain a normal zygote or embryo so far. The number of embryos though is still limited at least to the blastocyst stage and so we have to improve efficiency of the technique, but certainly it's very promising in terms of continuing the research and it certainly opens the option to women affected by reproductive age. It's not only aimed at women that are older but it's also aimed at younger women, although it's a smaller percentage, that have cancer or underwent cancer treatment. In this case, they would have no ovaries or an ovary with the inability to produce eggs so we would bypass the problem and give them a chance to have their own child. It would also be of interest for women with premature ovarian failure as well."

Hans van der Slikke, MD: "So it's useful for all women who don't have proper eggs but you still need some donor eggs for this procedure."

Gianpiero D. Palermo, MD: "So far we need to use the cytoblast from a donor and maybe one day we'll also be able to bypass this inconvenience but that's a first step. The fact that we are able to haploidize a somatic cell to create a gamete from a somatic cell would open a new frontier, I think, for reproductive medicine."

Hans van der Slikke, MD: "In theory, is it necessary to have a human egg cell."

Gianpiero D. Palermo, MD: "We have done some experiments using a somatic cell from a human in a mouse cytoblast and it haploidized. The problem is, for example, we should use other species because the mouse only has forty chromosomes whereas the human has forty-six."

Hans van der Slikke, MD: "You remove them?"

Gianpiero D. Palermo, MD: "Yes, you remove them but still because the cytoblast has information to create or to produce a spindle to support the addition of this chromosome for forty and not forty-six the incidence of abnormality would be very high. We wouldn't really correct aneuploidy; we would kind of produce a certain amount of aneuploid so we have to be careful with the specie we utilize. I think we have to gather more information in the human-human model with spare eggs and in the mouse-mouse model presently. Once we have some mouse offspring, I think, we will know more about the safety of the procedure and how reliable and feasible it is."

Hans van der Slikke, MD: "When do you expect this kind of results?"

Gianpiero D. Palermo, MD: "I hope in the next few years; hopefully, within five years we'll be able to apply the procedure. It could be earlier, I just want to be realistic."

Hans van der Slikke, MD: "For women at this moment it's still in the far future."

Gianpiero D. Palermo, MD: "It's still at the experimental level."

For more information please see  Women with limited pregnancy options may benefit from researcher's work