Future Therapies: Eggs from stem cells

October 5, 2012Carole 7 Comments »

Many years ago, I had a conversation with a patient that stuck with me. One of our IVF patients wistfully asked me, “Can’t you just knock two eggs together to make a baby?” She was in a lesbian relationship and like most people in love, wanted to share a genetic link with her partner via their kids. They knew about sperm donation and taking turns being pregnant so they knew they could each have kids, even with the same sperm donor if they wanted. But what they really wanted was what most straight couples take for granted–the ability to make a baby by combining genes from both of them.

That wistful hope may actual become clinical therapy some day. Today, Japanese researchers announced that they successfully produced mice using eggs derived from stem cells. They used stem cells derived from mouse embryos (embryonic stem cells) and also from non-embryonic cells that were induced to return to the stem cell stage (induced pluripotent stem cells). The latter type, because it doesn’t involve the demise of embryos is obviously ethically simpler.

So here is what they did. They took these stem cells and induced them into a pre-egg cell type called primodial germ cell-like cells (PGCLCs). When the testes or ovaries are formed very early in fetal development, cells called primordial germ cells migrate into the future gonads and produce functional testicles or ovaries. So in the lab, scientist were able to produce functionally the  same kind of primordial cells. Similar to what normally occurs during fetal development, scientists mixed these primordial egg cells with other female gonadal somatic cells –meaning all the other non-egg layers of cells that coexist in an ovary.

What happened next is really cool. The  lab-made primordial germ cells (egg-precursor cells) and the surrounding follicle-ovary cells worked together to restore the architecture of the ovary. The scientists created reconstituted ovaries,  and the egg precursor cells went through the normal stages of x-reactivation, genetic imprinting erasure, formation of follicular cysts (also known as follicles)  and meiotic division. When these in-vitro produced ovaries were transplanted back into female mice without ovaries, actual early stage (germinal vesicle stage) eggs were produced. Germinal vesicle stage eggs (you may have heard them called GV eggs by your embryologist) are not mature enough for fertilization. So the scientists had to culture these GV eggs in maturation medium for a few days until they completed the maturation process. After in vitro maturation, these mouse eggs–originally derived from stem cell precursors– were used with IVF to create mice babies. So beginning with a non-egg stem cell from embryos or another tissue, scientists ended up with functional eggs that could be fertilized to create mouse babies.

What  possible clinical applications could arise from these mice studies? Theoretically, older women might benefit from these advances if functional eggs could be produced from stem cells later in life.  Cells from post-menopausal women could be changed back into stem cells and then these stem cells could be driven down the egg production pathway to create functional eggs. In theory, there would be no clicking biological clock- at least due to egg quality. Gay male couples could benefit because cells from one of them could be used to create eggs that could be fertilized by sperm from their partner.

What about lesbian couples? We can’t “knock eggs together” but  perhaps we can create sperm cells from stem cells. Human sperm cells have been  reportedly induced from stem cells as well. In 2009, UK researchers reported creating human sperm cells from embryonic stem cells. More recently, in August 2012, researchers at the University of Pittsburgh showed that they could produce early human sperm cells from stem cells derived from skin cells. In the future, one partner in a lesbian couple could provide skin-sourced stem cells that could be used to create functional sperm.  Two women could then have regular IVF to create their genetic child. As pointed out by an astute reader below, because any cells from a woman are only XX, without a Y chromosome anywhere, it would be impossible to generate a Y-bearing sperm so theoretically only female offspring could be produced.

Men who have lost the capacity to produce sperm due to cancer or other illness may someday have a chance to restore their genetic fertility as well if sperm could be derived from stem cells. Because the stem cells could, in theory be induced from non-gonadal cells in the body, it is not necessary that the male have any functioning testicular tissue per se- unless they are needed to provide the support cells for sperm development as needed in the eggs from stem-cell example.

Obviously, there are still many experiments to be done to show what works in mice can safely and effectively work in humans. Of course there will be ethical debates and probably regulation of these new scientific therapies when and if they are ever ready for clinical implementation. It may be difficult to get institutional review board (IRB) permissions for clinical trials to see if these new gametes actually make healthy kids or not. Hopefully, much animal and primate testing will be done before we even think about human trials. Some experts are pessimistic that this research potential will ever be realized as a clinical therapy.  Still, I can’t help but feel cautiously optimistic that new solutions may be on the horizon for infertility patients that can’t produce their own gametes for a whole host of reasons.

© 2012, Carole. All rights reserved.

7 Responses to this entry

  • Brave IVF Girl Says:

    My husband and I were talking about this story last night.

    One question I raised, and neither of us has heard addressed, is whether or not two women would only be able to create girl embryos. Since there’s no Y chromosome anywhere in play, even if sperm could be created, all embryos would be XX. Is my logic good?

  • Sue Says:

    My grandson was born with a congenital anomaly: anorchia. He has never had testes and will, at adolescence, have to begin HRT. My hope is that one day (30 years from now) he will be a candidate for stem cell sperm. My question is this, though: bc he never had sperm or testes, and thus would be without primordial cells, is there still potential for his genetic reproduction. I know he could adopt or use donor sperm but I just hope that he will at least have more choice, given the other obstacles he will deal with owing to his disorder.

  • Carole Says:

    Hi Brave IVF Girl,
    Your logic is right. Without a Y chromosome in any cells whatsoever, you can’t get a “starter cell” with a Y that you can reprogram into a stem cell and then an egg cell with the Y chromosome. That brings up another issue. Theoretically for a male, you would end up with some artificial egg cells that contain only a y chromosome and some with only an X. I have no idea if an egg with just a Y would work, because the egg is under the direction of maternal transcripts until the embryo is activated but these have always been X directed. So this might also favor the creation of girls if the Y eggs don’t work. Interestingly, a review of the primary article, not the news reports, does show that the researchers started with stem cells from female mice so I would have to say we don’t know if this could work even 50% of the time for XY individuals to make eggs. Obviously, there are a lot of questions to be answered before any of this becomes effective therapy for everyone that might want it. I will revise the post with these questions in mind. Thank you. Carole

  • Carole Says:

    Hi Sue,
    I am not sure. On the one hand, stem cells can be induced from any cell type. Skin cells were used to produce early sperm cells. I don’t know if transformation to a fully mature sperm cell would require helper or support cells that are usually part of the testicular environment to make functional sperm. Even if that were necessary, it might be possible to use “donor cells” from another male for the purpose of culturing/maturing the sperm. It’s way too early to predict whether any of these new discoveries will result in good clinical therapy but with a time frame of 30 years, it is possible for your grandson. Best Wishes, Carole

  • Sue Says:

    Ah. That makes sense. Thanks for your thoughtful reply.

  • Brave IVF Girl Says:

    Thanks for the followup! It’s such an intriguing topic – thanks for covering it.

  • Hope Says:

    Any news on this subject?

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