11 July 2012

Disputes over ovarian stem cells

For more than 50 years, it has been assumed that women and females of other mammalian species are born with a fixed number of eggs (oocytes) in the ovaries, the number of which gradually decreases during life. At the same time, the ovaries themselves are not capable of producing new oocytes.

However, in recent years, this dogma has been somewhat shaken. First, in 2004, Ji Wu from Shanghai Liao Tong University and Jonathan Tilly from the Massachusetts General Practice Clinic isolated cells from the ovaries of mice capable of dividing and giving rise to new oocytes. Earlier this year, Tilly announced that he had managed to isolate the same cells, called oogonial stem cells, from the ovaries of a middle-aged woman. These discoveries promise new opportunities in the treatment of infertility, as well as relieving women from anxiety about the depletion of the supply of eggs. However, like all other discoveries that contradict dogmas, they caused a lot of controversy.

The results recently obtained by scientists at the University of Gothenburg, working under the leadership of Kui Liu, have added fuel to the fire of controversy. With the help of fluorescent tags, they traced the fate of cells that supposedly give rise to oocytes during division, and found that this assumption does not correspond to reality.

According to Liu, his original intention was to reproduce the results obtained by Wu and Tilly. However, he was confused by the fact that they used antibodies to the DDX4 protein expressed by reproductive stem cells to search for their cells. However, this protein is not on the surface, but inside the cells, so their search with the help of antibodies is simply impossible.

Therefore, Liu and his colleagues decided to work with so-called "rainbow" mice, whose reproductive cells emit a green glow under normal conditions, which changes to red, orange or blue when the Ddx4 gene is activated. They identified several such cells and observed them for 72 hours. During this period, none of the cells entered the division phase and did not turn into an oocyte. The researchers found several oocyte-like cells, but they did not express Ddx4.

Tilly explains this by the fact that, contrary to Liu's statements, the DDX4 protein is expressed on the surface of some reproductive cells, in particular those identified by him and in stem cells. The search for cells in which the Ddx4 gene is activated, regardless of the localization of the resulting protein, led Liu to detect oocytes characterized by intracellular expression of the DDX4 protein. And the cells that were monitored, apparently, are immature oocytes, unable to divide at all.

Experts reacted ambiguously to the data published by Liu – they were divided into two opposite camps, representatives of one of which consider Liu's statement justified, and representatives of the other, on the contrary, claim that the results of his experiments do not allow making such conclusions. However, they all recognize that in this case conclusions should be formulated with great caution, and carefully planned additional studies are necessary to clarify the situation.

Article by H. Zhang et al. Experimental evidence showing that no mitotic active female germline progenitors exist in postnatal mouse ovaries is published in the journal Proceedings of the National Academy of Sciences.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of The Scientist: Ovarian Stem Cell Debate.

11.07.2012

Found a typo? Select it and press ctrl + enter Print version