Stem Cells May Help Turn Back the Biological Clock

In biology we learn that a woman has a set number of oocytes, or eggs, within the ovaries and over her lifetime there is no way to increase this number. However, a new report in Nature indicates that this may not be the case. Scientists at Massachusetts General Hospital published a paper in Nature Medicine on their work with a potential source of ovarian stem cells that can produce oocytes. (A news brief and reference to the article can be found here.)

This group had done extensive work with mice in the past, and claimed to have found ovarian stem cells. However, their work was met with skepticism. Now they have developed more sensitive techniques for distinguishing between a normal oocyte and a stem cell. They used a type of fluorescence sorting technique:

Their method, based on a technique called fluorescence-activated cell sorting (FACS), attaches a fluorescently labelled antibody to a protein, Ddx4, that is present on the outer surface of the stem cells but not on the surface of the later-stage egg cells or oocytes. The FACS instrument lines up cells in single file and sorts them one by one, separating the labelled ones from the rest; it also gets rid of dead or damaged cells, such as oocytes, in which internal Ddx4 might become accessible to the antibody. This method is more selective than previous isolation methods, which did not get rid of such cells.

The authors followed these mouse studies with human studies. They harvested oogonial stem cells (OSCs) from the discarded ovaries of six women between the ages of 22 and 33, or at prime reproductive age. These OSCs generated what appeared to be normal oocytes within the laboratory setting. The group has not confirmed that these oocytes are capable of being fertilized and producing an embryo, but the OSC-formed oocytes seem to have the genetic markers of normal oocytes. Follow up studies indicated that OSCs exist in ovaries of women that are in their 40s.

The article reports that possible uses are for IVF procedures and increasing a woman’s reproductive lifetime:

…it could mean an unlimited supply of eggs for women who have ovarian tissue that still hosts OSCs. This group could include cancer patients who have undergone sterilizing chemotherapy, women who have gone through premature menopause, or even those experiencing normal ageing…In addition, growing eggs from OSCs in the lab would allow scientists to screen for hormones or drugs that might reinvigorate these cells to keep producing eggs in the body and slow down women’s biological clocks.

As the article notes, by increasing a woman’s reproductive lifetime by five years, this would cover most women who opt for IVF.

These findings raise several ethical considerations:

  • Because these experiments would involve the formation of an embryo, funding must be from either private sources or in collaboration with the U.K. (with a license from the U.K. Human Fertilisation and Embryology Authority).
  • While the article reports that this procedure could slow down a woman’s biological clock in the sense that she could produce more oocytes into her forties, this does not mean that the rest of her body is younger or healthier. Pregnancy is hard on the body at any age, and some women, who have had children when they are over forty, have commented on the difficulties in managing the physical demands of pregnancy as well as the subsequent physical demands of early motherhood. Some women’s bodies can handle this better than others, but that varies. The health and safety of the mother should be considered beyond just the health of her particular oocytes.
  • We do not know the developmental consequences of producing a baby in this manner. There are delicate factors involved in the developmental process, some of which are still mysterious to scientists. There is no way of knowing if a baby conceived from these types of gametes will have developmental abnormalities until it is tried. For all we know, this procedure may go the way that mammalian cloning has gone where for every “healthy” clone there have been hundreds of botched clones. In the case of Dolly, some of the clones were allowed to completely gestate, but were born with severe deformities.
  • Lastly, conspicuously omitted from this article is that this would provide a ready supply of oocytes for embryonic stem cell research. One of the issues scientists run into in trying to conduct embryonic stem cell research is the limited supply of eggs. There are several ethical issues with harvesting eggs from reproductively healthy women, none-the-least of which are commodifying women by offering them financial compensation for usage of their body, as well as under-reported substantial health risks  associated with hyperovulation (see here for Jennifer Lahl’s documentary, Eggsploitation). These findings provide a way for scientists to circumvent some ethical roadblocks, but does not remove the overall ethical dilemma of producing and destroying embryos for scientific research.

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