Stem cell therapy for female Infertility: Dream or Reality?

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Rapid advancements in stem cell research have been a hope for the cure of several diseases and disorders including infertility. But a recent study by Swedish researchers from University of Gothenburg and Karolinska Institute questions the feasibility of female infertility treatment with stem cells.

The basic principle of stem cell therapy is to induce the pluripotent stem cells to differentiate in to lineage of cells or tissue of choice. Several researchers believe that stem cell technology could solve the problems of female infertility by generating new eggs (ova) from stem cells despite the fact that ova is present in a woman since her birth.

The research team led by Dr. Kui Liu and Dr. Jan-Åke Gustafsson proved that oogenesis does not occur from the germline stem cells in adult mice by in vivo cell-lineage tracing throughout their life time. “Ever since 2004, the studies on stem cell research and infertility have been surrounded by hype. There has been a great amount of media interest in this, and the message has been that the treatment of infertility with stem cells is about to happen. However, many researchers, including my research group, have tried to replicate these studies and not succeeded. This creates uncertainty about whether it is at all possible to create new eggs with the help of stem cells,” says Kui Liu, a researcher at the Department of Chemistry and Molecular Biology at the University of Gothenburg.

In their study researchers destroyed or ablated follicles or oocytes in a female transgenic mouse model Gdf9-Cre;iDTR by injecting diphtheria toxin. This transgenic mouse was engineered to specifically express receptors for diphtheria toxin in the follicles. These mice showed no oocytes or follicles development for a period of up to 12 months which is the end of reproductive life span.

In another experiment,Sohlh1-CreERT2; R26R and Foxl2-CreERT2 transgenic mice were injected with tamoxifen and analysed after 2 and 8 months. These mice were engineered to produce β- galactoside under the influence of Sohlh1 promoter which is active only in the meiotic-arrested immature oocytes of primordial follicles. Tamoxifen administration labels only a percentage of the immature oocytes. This allowed the scientists to measure the ratio of labeled and unlabelled oocytes over a period of time. No change in the ratio of labeled and unlabelled oocytes was observed between 2 and 8 months of tamoxifen-injected ovaries suggesting that no new ova or oocytes developed from the so called germ line stem cells in adult mice.

These findings conclude that the so called germ line stem cells in the female reproductive system are devoid of proliferation and cannot give rise to new ova in adults. “This shows not only that the use of stem cell research in the clinical treatment of childlessness is unrealistic but also that clinics should focus on using the eggs that women have had since birth in treating infertility,” says Professor Kui Liu leaving a blank hope on the effectiveness of stem cell therapy in female infertility.

Source: University of Gothenburg

The original publication can be accessed here.