Rejuvenating gonads with stem cells – Fertility Lab Insider

Harvard scientist Jon Tilly proposed a radical new idea about how eggs are produced that called for the existence of ovarian stem cells which could continually produce new eggs. Stem cells are accepted as essential to sperm production in males. In men, the sperm stem cells (called spermatogonia) produce daughter cells that either make the final end product (new sperm cells) or make more stem cells in a continuing cycle of renewal.

Although accepted as dogma in the male system, the dogma regarding the ovary denied the existence of a renewable stem cell that could continually produce new eggs. The existing dogma was that every baby girl is born with all the eggs she will ever have and her eggs continually die off with age and are lost monthly after puberty. The ovarian stem cells was believed to only produce a defined number of eggs for a short time during fetal development but then became dormant for the rest of the females lifespan.

The problem with this dogma was that Tillys accounting of eggs lost in his experimental systems always ended up with more eggs than expected. The only way he could reconcile this discrepancy was to allow for the existence of a small population of ovarian stem cells which were capable of reactivating and contributing some eggs to the total. Most of his science colleagues were sure that he was wrong. It took him four years to prove the existence of these reactivated stem cells in the ovary by showing that stem cells he recovered from an aging ovary could be induced to make eggs again.

Tilly used cells from aged mouse ovaries, exposing them to the cellular environment of younger mouse ovaries and reactivating or rejuvenating the old stem cells which then started to produce eggs again. If the same could be done in humans, old ovaries could be reawakened to produce eggs. This would be a huge advance in the treatment of infertility since ovarian aging is considered irreversible. The only current treatment option for old ovaries which no longer produce eggs is to do IVF using eggs from a younger donor.

Unfortunately, it will likely be years, if not decades, before these scientific findings in a mouse model are converted to clinical treatments for patients. The typical path for moving a scientific discovery from bench to bedside treatment is excruciatingly slow because the clinical treatment must be proven to be both effective and safe. For reproductive treatments which produce children, the safety and health of those children is the primary concern.

First, treatments must be shown to be safe for both mother and offspring in other animal models, especially other primates like rhesus monkeys and chimpanzees. In vitro experiments with rare donated human ovarian tissue would also be necessary. If all the animal research and in vitro human tissue work still looks promising, clinical trials might start in humans, if institutional review boards give approval for the proposed research in humans. Because in vitro fertilization research is not funded by NIH, and stem cell funding is subject to erratic funded by NIH or individual states, this research will be slower to yield new clinical treatments compared to other non-controversial areas like cancer research.

Although anyone reading this today is unlikely to benefit personally from this research, it still opens a small door to the possibility of new treatments for advanced maternal age that dont involve giving up the genetic link between mother and child.

You can read more about Tillys research in this BioTechniques article Where do babies come from?.

Another scientist, Karim Nayernia, professor of stem cell biology at Newcastle Universitys Institute of Human Genetics, is researching the use of spermatogonial stem cells to revive fertility in the male, after chemotherapy or disease. In mouse studies, he was able to use stem cells from bone marrow and coax it to become sperm stem cells called spermatogonia. Transplants of these new stem cells into mice whose testicles were depleted of stem cells allowed the mice to father offspring. In 2009, his research team reported that they successfully produced human sperm-like cells from embryonic stem cells in vitro. There remain questions about the health of the mice offspring so this research is a long way from clinical use, but offers the possibility of new treatments for male infertility.

Another researcher, Richard Behringer, professor of genetics at the University of Texas MD Anderson Cancer Center has been using stem cells to understand what makes us male or female. His research may one day allow same sex couples to have genetic children together. First, he took stem cells from male mice, cultured them in such a way to cause the X and Y chromosomes to separate in culture, creating some daughter cells that were XO, a genetic type that creates a female genotype due to lack of a Y chromosome. Genetic material from these XO cells was used to replace the genetic material inside a mouse blastocyst. A surrogate mother mouse carried the XO blastocyst and gave birth to a female pup. The ovary of the pup produced eggs that contained DNA from the feminized male stem cell. This female offspring mated naturally with male mice to produce offspring from (essentially) two males.

Dr. Behringer is also investigating techniques to introduce a second X chromosome into an XO cell, creating a female egg cell from a male stem cell. There are decades of basic biology research to be done here which will provide insights into how sex differentiation works. These preliminary experiments are decades away from clinical use and may never be implemented if society as a whole remains uncomfortable with using science to circumvent male-female procreation.

Reproductive research has always been controversial. IVF was considered amoral and possibly dangerous in the beginning and yet is widely accepted today. Public opinion tends to come around if a new medical intervention is effective and causes no harm. If nothing else, stem cell research is unlocking the most basic secrets nature has and although we cant predict what new fertility treatments, if any, might arise, it is certainly worth understanding reproduction at the cellular and molecular level. Stem cells are proving extremely useful for reproductive research.

2011, Carole. All rights reserved.

Posted on January 12, 2011 at 2:03 pmhttp://fertilitylabinsider.com/2011/01/rejuvenating-gonads-with-stem-cells/http://fertilitylabinsider.com/2011/01/rejuvenating-gonads-with-stem-cells/trackback/Categorised under : Ethical Issues , Fertility Preservation , Inside the Lab , Repro Bio 101Tagged with : eggs from stem cells , reproductive research , sperm from stem cells , stem cell research

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