Is it possible to remove the DNA from an unfertilized female egg and replace it with the DNA from a sperm cell carrying the X-chromosome?
March 13, 2009 4:47 PM   Subscribe

Regarding humans, is it possible to remove the DNA from an unfertilized female egg and replace it with the DNA from a sperm cell carrying the X-chromosome (perhaps using a process similar to nuclear transfer)? After doing this, could the egg be fertilized by the sperm of a different male and implanted into a surrogate mother, thus creating a child that is the biological child of two males?

Could a similar process be used to create a child from two females? (Obviously their child would be female because there would be no Y-chromosome involved.)

Is it probable that this will be possible/common/affordable once science progresses?
If all of this is indeed possible, why are these processes not commonly utilized by gay couples?
posted by Houyhnhnm to Science & Nature (12 answers total) 4 users marked this as a favorite
The process of haploidisation has allowed scientists to create mice, so far, with genetic material from two female parents. I am looking for evidence of success with two male parents, but having trouble finding it.
posted by notquitemaryann at 5:11 PM on March 13, 2009

It's possible eventually, I guess, but you could accomplish essentially the same thing right now by taking two eggs from a given woman, fertilizing one with the sperm of one man and the other with the other's, letting each divide several times, pulling one cell from each to test and be sure they were the same sex, then pushing the two bunches of cells together so that they form a single cell mass and implanting that in a surrogate.

Such an individual might even have genetic advantages over typicals.
posted by jamjam at 5:18 PM on March 13, 2009

In reading your question, I was curious about whether there were differences in male and female DNA beyond the X/Y chromosome. Turns out there are some issues with genomic imprinting from maternal and paternal sources which lead to birth defects if there's not one of each on certain parts of the DNA. Obviously they could try to find a way around it, but it certainly complicates the issue.

Also, since the method you linked to is part of cloning efforts, there would probably be social/religious arguments against the process you're suggesting if it's seen as unnatural influence on creating humans (as cloning is).
posted by parkerjackson at 5:18 PM on March 13, 2009

Genotypicals, I should say.
posted by jamjam at 6:00 PM on March 13, 2009

Theoretically? I think so. Practically? No, at least not yet. Remember Dolly? The way she was made was by doing something similar to what you're talking about, taking the genetic material from one cell, and inserting it in another. That's about as far as we've come so far. I'm pretty sure no such tests have been done on human beings yet.
posted by kingjoeshmoe at 6:11 PM on March 13, 2009

pulling one cell from each to test and be sure they were the same sex, then pushing the two bunches of cells together so that they form a single cell mass and implanting that in a surrogate.

I'm no biologist, but it seems like the sex of the two embryos would be the least of your worries. Even if the embryos were to successfully combine (which I doubt -- at the most you might end up with unrelated conjoined twins. Weird!), the resulting embryo would contain two unique genotypes.
posted by i_am_a_fiesta at 7:22 PM on March 13, 2009

So, in mice, at least, it is quite possible. The words to search for are androgenetic embryos. Then ignore all the hairloss ads, as androgenetic alopecia seems to be the internet's primary concern.
But essentially, yes, they inject one sperm nucleus, then suck out the maternal nucleus, leaving the good cytoplasmic stuff, like mitochondria, in and then fertilize with another sperm using IVF.
I would hazard that, just as parkerjackson suggests, the imprinting imbalance arising from two paternally imprinted alleles would be problematic for both the fetus and the surrogate, although the mice seem to do alright. This may be the primary limitation on bringing this to the human level.
I have a dim recollection, although I can't find the paper now, of the converse: enucleated sperm injected with oocyte nucleus. In theory that would be quite possible, but consider the numbers in this case... oocytes are big expensive cells to make, and quite finite for any given genome (females make all their eggs before they're born) and collecting them is a bitch. Whereas sperm are continuously replenished and trivial to collect in quantity. As any fertilization event requires an abundance of sperm, to assure quality of outcome, the production of enough haploid sperm that you injected with maternal haploid nuclei is prohibitive, given the source of them (oocytes).
With the way our gametes are set up, it seems much more likely that there would be a androgenetic human embryo made before a gynogenetic one.
posted by Cold Lurkey at 7:32 PM on March 13, 2009

i_am_a_fiesta: I think you'd end up with a genetic mosaic / chimera. This is actually kind of common, as I understand it, though the cells would be siblings, not completely unrelated.
posted by hattifattener at 8:10 PM on March 13, 2009

If my recollection about Dolly's genesis is right, that Wikipedia article on Nuclear Transfer linked in the original question is incorrect.

I believe that the nucleus of a fertilized ovum was removed (not just the DNA) and was replaced by a nucleus from a somatic cell. Been a long time since I thought about that though.
posted by Sublimity at 8:30 PM on March 13, 2009

Mrs. Princelyfox says:

My University doesn't have access to Genesis, Cold Lurkey, so I can't speak to that article. As you have described it Houyhnhnm, my answer is "no." However, it may be possible. But first let me explain why it won't work with humans.

Placenta formation is driven by paternally imprinted genes from sperm. When the maternal signals are missing due to severe chromosome abnormalities caused from advanced maternal age, sperm imprinting directs development of all embryonic tissue to exclusively form placenta tissue which is termed a hydatidiform mole. No fetus is formed. If the levels of genes expressed by sperm imprinting are elevated higher than normal (such as by two sperm fertilizing an enucleated egg) and the maternal genes are absent, then the mole can become invasive leading to gestational trophoblastic disease. The implantation becomes overly aggressive leading to tumors which can metastasize and have to be treated with chemotherapy and possibly hysterectomy.

This technique is theoretically much more realistic for two females. Assuming you first can get two haploid nuclei into an egg from two women (which would require parthenogenetically activating the oocytes to force expulsion of the second polar body to get them haploid), then the resulting embryo would not form placental tissues. There is a workaround for this in mice developed for making transgenic mice knockouts termed tetraploid rescue.

So, Houyhnhnm, in summary one sperm nuclei would need to be remodeled. This is theoretically possible via either Xenopus oocyte extract , the three genes used in iPS cells , or by serially transplanting the sperm nuclei into multiple oocytes. The difficulty with all these is the mechanism of delivery. In theory, you could make a sperm nuclei preparation, then in vitro transcribe and translate Sox2, Oct4 and Klf4 and incubate those proteins with the sperm nuclei to remodel it, then inject the nuclei into enucleated eggs, and then add the second male’s sperm. Prior to implantation, you would have to do preimplantation genetic diagnosis to avoid the YY embryos that would be made. (I have no idea how YY embryos would develop – the X chromosome has some really important genes for neural development so you’re looking at mental retardation if they are even viable.)
posted by princelyfox at 9:24 PM on March 13, 2009 [3 favorites]

Re: princelyfox

I'm not a reproductive biologist, your answer was much more well informed than mine, but as to your final point, I know I've read in multiple places that YY or YO embryos do not develop.
posted by CTORourke at 11:39 PM on March 13, 2009

Here is a similar thread that I just found.
posted by Houyhnhnm at 4:37 PM on March 14, 2009

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