Artificial Egg Technology May Advance Fertility Treatment and Produce Children with Two Biological Fathers

Reproductive technology may soon take parenting where no man has gone before. In quoting the intro to the original Star Trek, before the reboot of the show got more gender inclusive (“where no ONE has gone before”), I don’t mean to be sexist. I’m talking about biotechnology that may be poised to enable babies to be produced from two same sex parents whose chromosomes intermingle the same way as those of mother and father in nature. This looks as though it will happen with two fathers long before it happens with two mothers.

Let’s make sure that we’re on the same page before diving more deeply into the discussion, since biotechnology has already provided scenarios on which babies are born from more than two parents. The oldest way for this to happen dates back to ancient times. A man unable to conceive a child with his wife blames the wife and simply takes a second wife, or a concubine, and tries to produce a child with her, and then, in a sense, the baby has one father and two mothers. This happens in the Biblical story of Abraham, whose wife, or principal wife (depending how you read the story), Sarah, cannot conceive, so Abraham sleeps with a different wife or concubine (also depending on how you read the story), Hagar, who gives birth to a son, Ishmael. There’s quite a bit of sibling rivalry and inter-wife rivalry in this classic story, but it reflects actual family situations in the Middle East, during the Iron Age, when the story was written down.

Moving forward to the late 19th century, the advent of artificial insemination led to a scenario called surrogate motherhood. Nearly a century before in vitro fertilization (IVF) was devised, the method of harvesting donated semen from a man and injecting it into the uterus of a woman was first tested. The woman could be the sperm donor’s wife, opting to be inseminated this way in an attempt to become pregnant after not getting pregnant the natural way. She could also be single woman who doesn’t know the donor, or could be with a man who is sterile. During the 20th century, researchers would improve this method by spinning the semen in a centrifuge, in order to concentrate the sperm cells and remove urine and other fluids, before injecting it into the woman’s uterus. Alternatively, especially if a couple could not have a child on account of the woman having a reproductive health issue, the man’s sperm could be used to impregnate a surrogate mother, a volunteer, usually paid, to carry the pregnancy for the couple, but then not be involved with the child. So in that sense the child would have three parents: a father, a legal mother who raises the child, and a biological mother, the surrogate, who carried the pregnancy.

IVF came on the scene in the late 1970s. This was useful in cases when neither sexual intercourse, nor artificial insemination, nor hormonal treatments, were enough to compensate for a couple’s fertility problems. If a woman could produce ova, but some problem always interfered anywhere in the process of sperm cells reaching an ovum as they traveled through the fallopian tube, the ovum being fertilized to produce a zygote, and the zygote developing over the course of five to six days into a blastocyst (the entity that implants into the endometrium of the uterus), fertilization could be carried out in the laboratory. In modern-day IVF, typically the aspiring mother receives hormonal therapy to help her produce multiple ova each month. The ova are harvested directly from the ovary through a needle and multiple ova are fertilized in the lab with the aspiring father’s sperm. Any fertilized eggs, zygotes, are then observed over the course of a few days, as they undergo cell division and develop, or some or all of them are vitrified (cooled extremely rapidly to make them like glass) to enable cold storage over time. Embryo transfer (ET) is the process of taking one or more such embryos and injecting them through a special tube, through the aspiring mother’s cervix, to optimal spots within the uterus, using ultrasound guidance. Usually this is done with embryos that have reached anywhere from the four or eight cell stage to the blastocyst stage. They can be embryos created just a few days before, or embryos that have been revived after some period in cold storage.

IVF-ET also is the technique used when the aspiring mother herself cannot produce ova. In such cases there is an egg donor and resulting embryos can be transferred to the aspiring mother, if she has a uterus, or they can be transferred into a surrogate mother, who may or may not be the egg donor. Thus, with IVF, there can be a legal father and a donor father, and a legal mother, a donor mother, and a surrogate mother.

But technology also allows for another kind of mother called a mitochondrial mother. Mitochondria are organelles that you have in most of your body cells. Their role is to generate energy in the form of a molecule called ATP. Mitochondria have their own DNA, their own genes, separate from the DNA of the cell nucleus, because thee ancestors of mitochondria were independent, bacteria-like organisms billions of years ago. Mitochondria reproduce on their own and all of your mitochondria come from your mother. Your father contributed half of your nuclear genes, your mother the other half of your nuclear genes, but she also contributed all of your mitochondrial genes. On account of some rare conditions in which mitochondria are sick, there is now a process for creating an egg whose mitochondria come from one donor and whose nuclear genes come from the aspiring mother. With IVF, these two genomes can be combined with the aspiring father’s genome.

This brings us to the next innovation, which utilizes cloning technology, reproductive cloning which can enable an aspiring mother who cannot make her own ova to have an ovum produced anyway from the genes in one of her body cells, such as a skin cell. Doing this is already very complicated legally, particularly in the wake of the Supreme Court of the United States (SCOTUS) decision on the Dobbs versus Jackson Womens Health Organization abortion. Just to remind you, the Dobbs case regards a Mississippi law prohibiting abortions after 15 weeks gestation. The majority decision ended up, not only upholding the Mississippi law, called the “Gestational Age Act,” but also overturning the Roe V Wade decision of 1973. This may place all reproductive technology in the crosshairs, because reproductive technology creates human embryos, many of which never turn into babies (just like embryos in nature). Currently, US federal law prohibits federal funds from being used to support reproductive cloning and related research, but some US states have much more liberal policies.

Oregon is one such state. Researchers based at Oregon Health Sciences University (OHSU) recently succeeded with a modified cloning process in mice. Normally, the way to create a clone is to take an ovum (an egg), remove the genetic material (the chromosomes) from its nucleus, and replace that nuclear genetic material with the genetic material from a body cell, such as a skin cell. This produces a cell that is diploid, meaning that it has two of every chromosome, instead of being haploid (having just one of each chromosome) like an ovum or a sperm cell. Such a cloned cell can then start to divide, just like a zygote, and form an embryo that can be implanted into a woman’s uterus. If the clone were made from the woman’s own body cell, the child will be a clone of the mother. Genetically, it will be identical to the mother, so it will be a girl who looks very much like the mother looked when she was a child. If the clone were made from the aspiring father’s body cell, it would be a boy who looks like the father looked when he was a boy. Either way, it would be like having a twin who is a generation younger than you. Not everybody likes that scenario and would rather have a child who is a genetic blend of both parents.

But in the mouse study, the OHSU team added another step. Once the genetic material, the genome, of the donated ovum is replaced with the genetic material of a body cell, the cloned cell can be made to go through a process called haploidization, in which its genome is cut in half so that it has just one of each chromosome, instead having paired chromosomes. Now, it is haploid, just like an ovum that a female produces each month from her ovaries, but its haploid genome comes from a body cell. This is useful in fertility treatment, if a woman cannot ovulate, or otherwise be made to produce ova. But since the genome of the haploid cloned cell comes from a body cell, such as a skin cell, the donor of that genome can be either female, or male. Then, it can be fertilized, in vitro, with sperm from an aspiring father, but if the skin cell was from a male —as it was in the OHSU mouse study— then the biological mother, is actually a father too. The embryo produced has two biological fathers and no biological mother, although, until artificial womb technology is ready, there must be a surrogate mother to carry the pregnancy.

So what about having two biological mothers —let’s specify two biological nuclear mothers, to avoid the scenario of a mitochondrial donor— and no father? For this to happen, the technique would have to create a haploid clone from one mother, which could involve the same technique that we described, since a skin cell can be used from either sex, but then fertilize that haploid, ovum-like, cell with a cell containing a haploid genome from a different woman. Since both gamete-like haploid cells would come from females, neither could supply a Y chromosome, so this process would produce only girl babies. Unless, of course, technology advances to the point at which genetic material comprising the Y chromosome of a male chromosome donor can replace, safely, one of the X chromosomes. Eventually, this may be possible with some advanced form of CRISPR genome editing.

David Warmflash
Dr. David Warmflash is a science communicator and physician with a research background in astrobiology and space medicine. He has completed research fellowships at NASA Johnson Space Center, the University of Pennsylvania, and Brandeis University. Since 2002, he has been collaborating with The Planetary Society on experiments helping us to understand the effects of deep space radiation on life forms, and since 2011 has worked nearly full time in medical writing and science journalism. His focus area includes the emergence of new biotechnologies and their impact on biomedicine, public health, and society.

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