PhD student, Karolinska Institutet
Characterisation of human ovarian tissue cells
Female fertility has been widely accepted as a finite window of opportunity, due to the limited and depleting source of ovarian follicles present during normal aging. Recent reports of putative oogonial stem cells (OSCs) have questioned this prevailing dogma and stimulated research and intervention efforts in the realm of fertility and reproductive medicine. By studying these reported putative OSCs isolated from human ovarian tissue, we aim for a better understanding of the underlying mechanisms of female fertility. By dissecting cell identity and function from the heterogeneous milieu comprising primary isolated ovarian tissue, I intend to elucidate whether the currently practiced OSC-based infertility treatment should be recommended or further scrutinized for efficacy. Currently I am characterizing the diverse unknown stromal cell types found in human ovarian tissue, based on surface protein expression patterns and in vitro functionality. Efforts in exploring signaling pathways involved in ovarian follicle activation and death due to chemotherapy are taken to unravel cellular interactions and mechanisms in human ovarian tissue.
Taking everything into account, my work aims in gaining fundamental knowledge in the diverse cell types composing human ovarian tissue, better understanding their underlying mechanistic interactions, and realizing their true potential for applications in infertility treatment.
Abstract: Germline stem cell research over the last decade has brought into question one of the basic tenets of reproductive biology that women are born with a finite number of oocytes without the potential for renewal. Evidence for the existence of oogonial stem cells in the postnatal ovary has gained momentum, but skepticism remains.Several research studies claimed that they have identified functional oogonial stem cells in the postnatal ovary of several different species including humans. The scientific community has questioned both the methods and significance of these studies.Many speculate that germline stem cells could make a significant impact on the treatment of female infertility. However, this field of research is still in its infancy. There is still much to learn about the biology of oogonial stem cells and their potential clinical application. More research is needed before oogonial stem cells can become a viable treatment modality for women with infertility.
Pub.: 17 Apr '13, Pinned: 15 Sep '17
Abstract: Whether the adult mammalian ovary contains oogonial stem cells (OSCs) is controversial. They have been isolated by a live-cell sorting method using the germ cell marker DDX4, which has previously been assumed to be cytoplasmic, not surface-bound. Furthermore their stem cell and germ cell characteristics remain disputed. Here we show that although OSC-like cells can be isolated from the ovary using an antibody to DDX4, there is no good in silico modelling to support the existence of a surface-bound DDX4. Furthermore these cells when isolated were not expressing DDX4, and did not initially possess germline identity. Despite these unremarkable beginnings, they acquired some pre-meiotic markers in culture, including DDX4, but critically never expressed oocyte-specific markers, and furthermore were not immortal but died after a few months. Our results suggest that freshly isolated OSCs are not germ stem cells, and are not being isolated by their DDX4 expression. However it may be that culture induces some pre-meiotic markers. In summary the present study offers weight to the dogma that the adult ovary is populated by a fixed number of oocytes and that adult de novo production is a rare or insignificant event.
Pub.: 16 Jun '16, Pinned: 15 Sep '17