Are Human Females Born With All The Eggs They Will Ever Have?
April 14, 2009 by Ryan Ward
Here’s something you’ve probably heard, or believe to be true: When human females are born, they already have the total number of eggs that they will ever have for the course of their lives. This idea is so pervasive and dogmatic in the general public that it verges on absolute fact. And one can appreciate why- a simple search of the internet finds many posts supporting this position. But is this true? Are women born with all the eggs they will ever have? The answer is, LIKELY NO!
It now appears that mammalian females produce NEW eggs after birth and into adulthood. There are two important studies that deserve some attention. The first was published in 2004 in the journal Nature. The authors noticed that the follicles (the structures that contain the oocyte/egg) within the mouse ovary naturally degenerate at a rate that would predict complete exhaustion of their follicular reserve by early adulthood. This means that without some replenishment of follicles and oocytes, female mice would no longer have any remaining oocytes/eggs shortly after reaching sexual maturity. Knowing this was not the case, the authors went on to identify Germline Stem Cells which could generate new germ cells (eggs) in adult female mice. Amazingly, when fluorescently labeled ovaries were surgically implanted into normal (non-fluorescent) mice, fluorescent eggs could be seen within the normal ovary indicating that the fluorescent Germline Stem Cells had produced eggs in the normal mouse.
Just recently, another group reported that they could harvest mouse Germline Stem Cells from both newborn and adult female mice, and grow them long term in vitro (in culture dishes). Importantly, they could reinject them into ovaries of sterile mice and restore fertility in the recipients. As evidence fluorescent pups were born from previously sterile, non-fluorescent mothers who were injected with fluorescent Germline Stem Cells.
Together these studies indicate that female mammals have Germline Stem Cells which produce eggs long after birth. Moreover, these Germline Stem Cells can be harvested, studied and grown in vitro, and injected into ovaries to restore fertility of recipients. While both these reports used mice in their experiments, it’s very likely that human females have similar Germline Stem Cells that could be harvested, stored and used to restore fertility of a patient. You can quickly appreciate the implication of this finding: the future of reproductive technology may not be limited to in vitro fertilization and implantation, but may also include the use of Germline Stem Cells to restore fertility, in particular for people who are sterile from cancer therapy. Conceivably, Germline Stem Cells could be harvested from patients before rounds of chemotherapy and radiation, and then reinjected after treatment. An important medical advance, particularly for pediatric cancer survivors!
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Rett Syndrome and induced Pluripotent Stem cells goes “Green”
June 17, 2009 by Aaron Cheung
Stem cell researchers at The Hospital for Sick Children have now devised a method, reported in the scientific journal Nature Methods, that will facilitate the generation of induced Pluripotent Stem (iPS) cells. I have previously blogged about the promise of iPS cells (see related articles). iPS cells are cells which have been reprogrammed from a differentiated somatic cell (such as your skin cells) to a pluripotent stem cell (like an embryonic stem cell, only that you don’t need to use embryos!). The generation of iPS cells is inherently very rare which occurs at a frequency of about 0.01% meaning you can generate about one iPS cell line out of hundred thousand cells. Out of which, many lines fail to satisfy the different rigorous tests necessary to be given the prestigious name of “iPS cell”.
A group led by Dr. James Ellis, and lead author Dr. Akitsu Hotta, at The Hospital for Sick Children has generated a reporter, named EOS, that will facilitate the generation of iPS cells for both mouse and human. The reporter has DNA elements (called promoters) that will drive the expression of a fluorescent protein (GFP) and an antibiotic resistance gene (puromycin) that will only turn on in pluripotent stem cells, but remain off in differentiated cells. Therefore, scientists can now generate iPS cells from different sources and the iPS cells will literally “light up with a green colour” once reprogramming has been achieved. Furthermore, by adding puromycin to your culture, it will keep the iPS cells in a pluripotent state as iPS cells will normally spontaneously differentiate.
To demonstrate the applicability of EOS, Ellis also derived iPS cells from patients who have a neurodevelopmental disorder called Rett Syndrome. Rett Syndrome is an Autism Spectrum Disorder which affects almost exclusively females at an incidence of 1 in 10,000 and is one of the leading causes of mental retardation in girls. These Rett Syndrome iPS cells were green when placed under a fluorescent microscope and Ellis demonstrated that neurons can be generated from these Rett Syndrome iPS cells, the cell type affected in Rett Syndrome.
In conclusion, the EOS reporter will facilitate the generation of iPS and will be particularly useful for new labs going into this rapidly developing field. Furthermore, Rett Syndrome iPS cells that were also generated in this study will be invaluable for future drug screens that may be beneficial to those with Rett Syndrome.
Article:
Hotta, A. et al. Isolation of human iPS cells using EOS lentiviral vectors to select for pluripotency. Nature Methods 6, 370–376 (2009).
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Breakthrough of 2008 – Reprogramming
A New Era for Disease Modeling and Drug Screening
Some of our experts
Stem Cell Origins
Cancer stem cells
Stem Cells and the Nervous System
