| title: | Genetic variations in genes involved in regulation of folliculogenesis: implications for normal, abnormal and induced folliculogenesis |
|---|---|
| reg no: | ETF6498 |
| project type: | Estonian Science Foundation research grant |
| status: | accepted |
| institution: | University of Tartu |
| head of project: | Andres Salumets |
| duration: | 01.01.2005 - 31.12.2008 |
| description: | The objective of this project is to study the variations of genes regulating the ovarian function and to describe their role in normal, pathological and induced folliculogenesis. The folliculogenesis is rather complex process leading to the ovulation of mature oocyte. The very first stages of folliculogenesis are initiated by growth factors other than gonadotropin hormones (follicle stimulating hormone - FSH and luteinizing hormone - LH). However, further maturation of tertiary follicles is depending on the effect of gonadotropins. The FSH regulates estrogens synthesis in granulosa cells of FSH-sensitive tertiary follicles. The estrogens along with FSH are essential for terminal maturation of dominant follicle in follicular phase of natural menstrual cycle. The secretion of FSH is modulated by the endocrine effects of estrogens and inhibins as well as by para- and autocrine regulation of activins and follistatin. Normally, only one follicle ovulates during each menstrual cycle, but in rare cases more than one oocyte mature till ovulation. The latter causes the dizygotic twins to be born. It has been shown, that mothers of dizygotic twins are often characterised by higher values of serum FSH, which could be the reason for them to ovulate more than one oocyte. In current project, we identify the variations of folliculogenesis regulating genes (FSH and LH β-subunits, FSH and LH receptors, subunits of inhibins and activins, and follistatin) in the group of women with dizygotic twin babies. The study gives us additional knowledge to understand more about the regulatory mechanisms of folliculogenesis. The knowledge about the process of folliculogenesis is necessary for reproductive medicine, as ~1/3 of all infertility problems are caused by the failure in follicular maturation. Polycystic ovarian syndrome (PCOS) is the most prevalent endocrinopathy, which leads to the disorders of folliculogenesis and infertility. PCOS is often characterized by the increased ratio of LH/FSH serum values. Elevated values of LH stimulate ovaries to produce more androgens, while the conversion of the androgens into estrogens is insufficient. This dysregulation of gonadotropins and steroid hormones secretion initiates a number of tertiary follicles to mature but no dominant follicle is selected. PCOS is a multifactorial and polygenic disease, where important part of the genetic susceptibility is conferred by the genes regulating the function of gonadotropins. In this project, we study the polymorphisms of candidate genes (FSH and LH β-subunits, FSH and LH receptors, subunits of inhibins and activins, and follistatin) in correlation of the susceptibility to develop PCOS. To understand the regulation of folliculogenesis improves the treatment for infertility, the procedure of in vitro fertilisation (IVF). The expected outcome of IVF depends directly on the effectiveness of FSH stimulation of folliculogenesis. In our study we identify the complex genotype containing the FSH receptor gene, estrogens synthesizing aromatase gene and genes for estrogens receptors, in the group of the infertile women. We use the identified genotype to describe the relationship between the patient's genotype and the effectiveness of induced stimulation. The outcomes of the study have also a great importance for future developments of infertility treatment, allowing to individualise the person's folliculogenesis stimulation protocol and making IVF procedure safer and more effective. |
| project group | ||||
|---|---|---|---|---|
| no | name | institution | position | |
| 1. | Signe Altmäe | University of Tartu | Ph.D student | |
| 2. | Tiina Kahre | TÜ Naistekliinik; TÜ Molekulaar- ja Rakubioloogia Instituudi | 1. Laboratory doctor/paedriatician 2. Scientist | |
| 3. | Peeter Karits | Nova Vita lastetuse ravi kliinik | Gynecologist | |
| 4. | Helle Karro | TÜ Naistekliinik | head of the department | |
| 5. | Kadri Matt | TÜ Naistekliinik | docent | |
| 6. | Maire Peters | TÜ Naistekliinik | Scientist | |
| 7. | Andres Salumets | University of Tartu | Scientist | |