Projects / Programmes
New insight into the human ovary function: embryonic stem cells and oogenesis in vitro ?
| Code |
Science |
Field |
Subfield |
| 3.05.00 |
Medical sciences |
Human reproduction |
|
| Code |
Science |
Field |
| B000 |
Biomedical sciences |
|
Human * ovary * embryonic stem cells * in vitro oogenesis
Researchers (20)
Organisations (2)
Abstract
Pluripotent embryonic stem cells have already been confirmed in the different adult human tissues and organs - bone marrow, heart, liver, and testis. They persist in the adult human body from the embryonic period of life. So the human embryos are not the only source of pluripotent stem cells. The aim of this research project is to isolate embryonic stem cells from the adult ovarian surface epithelium in postmenopausal women and young women with preterm menopause (premature ovarian failure) with no naturally present follicles and oocytes. Embryonic stem cells will be confirmed in different ways - by analyses of surface antigens, transcription markers, and by in vivo differentiation into the cells of all three germ layers (endoderm, mesoderm, and ectoderm) in the mouse model. Stem cells will be retrieved by the scraping of the ovarian surface epithelium. In the next step cell culture will be set-up by scraped cells and in vitro development of early oocytes - oogenesis will be followed. Oocytes will be confirmed by the expression of genes, characteristic for germ cells and oocytes. Besides, the genetic status of in vitro developed oocytes will be evluated. The proposed research project provides a new approach to the understanding of the ovarian infertility due to the female age and premature ovarian failure in young women. Oocytes developed from the ovarian stem cells could be usefull for the in vitro fertilization process in the far future. Pluripotent embryonic stem cells isolated from the human ovaries could be also usefull for the autologous treatment of degenerative diseases in the future.
Significance for science
Research results achieved with the frame of this research project are original and important in the international and national research environment. Results are internationally important because for the first time they confirm the presence of embryonic-like stem cells in adult ovaries of women with no naturally present follicles or oocytes: young infertile women with premature ovarian failure and postmenopausal women. We have successfully isolated stem cells from adult human ovaries by scraping the ovarian surface epithelium, and have confirmed the expression of some of the markers of pluripotency. In the lab we established the conditions which induced the development of autologous ovarian stem cells into the direction of primitive oocyte-like cells expressing several genes of pluripotentcy and oocytes, but not all of them.
It is stimulating that the regenerative potential of ovaries was confirmed in women infertile for premature ovarian failure in whom until the only treatment they could be offered has been in vitro fertilization of donated oocytes. The results are very stimulating and call for continuation of this research based on new findings in the field of in vitro oogenesis provided by research of mouse and human embryonic stem cell lines, and our own original findings obtained in this research project which for the first time permitted to study autologous in vitro oogensis that might result in finding a new approach to severest forms of ovarian infertility treatment in the future. These findings might also bring new insights into the understanding of aggressive ovarian tumor formation, especially in older women.
It should be pointed out that in spite of the big step forward taken thanks to this research project, the research work should be continued. The process of in vitro maturation of oocytes is very difficult and complex, and hard work in the country and abroad will be needed before our achieving our goal, i.e. the development of mature and competent autologous oocytes which would be useful in the in vitro fertilization programme for autologous treatment of severe ovarian infertility instead of using donor oocytes, which currently represent the only treatment option for these women.
Significance for the country
This research project is also important for the development of Republic of Slovenia. The stem cell research is a new and fast developing activity. This research project represents one of a few research projects in this field in Slovenia, and brings some pioneering work in isolation, confirmation, culture, and differentiation of embryonic-like stem cells in adult human tissues and organs, in the ovaries, in particular. In the frame of this research project, some new collaborations have been established thus enabling the development of new methods which otherwise would not have been established. For example, single-cell gene expression analyses by RT-PCR technology were performed for the first time. The financial support sufficed for some basic equipment for stem cell research, which will eventually be upgraded.
In this research project young researchers - the first generation of young experts and doctoral students - have been educated starting their scientific career by a qualitative stem cell research and potential implementation of stem cells for cell therapies and treatment of degenerative diseases in the field of regenerative and reproductive medicine. Our knowledge has also been transferred to the next generations within the curriculum of undergraduate study of medicine, and especially of the postgraduate study of Biomedicine at the Faculty of Medicine, University of Ljubljana.
With the results achieved in the frame of this research project the reputation of Slovenia country has been increased and some long-term international collaborations have been established.
Most important scientific results
Annual report
2008,
2009,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2008,
2009,
final report,
complete report on dLib.si
