The research group “Reproductive biology” has a well equipped research laboratory at the Department of Women’s and Children’s Health/Obstetrics and Gynaecology Department. The laboratory is equipped with facilities for cell culturing, contractility measurements and biochemical analysis such as qPCR, immunohistochemistry and Western blot. At the laboratory there are senior researchers, PhD-students, post docs, students doing their master's thesis and technicians.
The research group has two sub-groups:
Temporarily stopping the levonorgestrel analysis
Inquiries and information regarding levonorgestrel analysis, please refer to Torbjörn Åkerfeldt, Clinical Chemistry and Pharmacology, Akademiska Laboratory, Akademiska sjukhuset, firstname.lastname@example.org.
Clinical and experimental reproductive biology
Gynaecology is an old Greek word that means the knowledge about diseases associated with the female reproductive organs. This comprise teenage gynaecology, contraceptives, abortions, miscarriages, infertility, early pregnancy, menstruation disturbances, sex hormone related diseases, urine incontinence, gynaecological cancer and menopause/post menopause.
In our group we have several projects involving parts of this panorama of problems and diseases related with the female reproductive organs and functions.
Our main research projects
The human endometrium
changes during the menstrual cycle, and this is especially true for the luteal phase. In the mid-luteal phase the endometrium is undergoing changes aiming at optimizing the conditions for the implanting blastocyst and subsequent placentation. If implantation does not occur the endometrium will undergo changes that will lead to menstruation. Despite a lot of efforts throughout the years to characterize the human endometrium, there is still not much known concerning changes in gene and protein expression through the menstrual cycle. The aim of our study is to determine changes in gene and protein expression throughout the menstrual cycle by doing gene micro array analysis and proteomic approach. We are also studying the regulation of endometrial angiogenesis.
Endocrine disrupting chemicals and female fertility functions
There is a great lack of knowledge concerning possible effects of endocrine disruptors (EDCs) on human fertility functions such as effects on the human endometrium. The European Union has recently adopted a program (REACH) http://ec.europa.eu/environment/chemicals/reach/reach_intro.htm where it is stated that possible effects of about 30 000 chemicals on human fertility functions should be evaluated. Our project has been a part of an EU-project (http://www.reprotect.eu/) where the aim was to develop alternatives to animal testing of effects of EDCs on reproductive functions. The primary objective is to study the mechanisms and effects of endocrine disruptors (EDCs) on the proliferation, growth and gene expression of cultured primary cells from the reproductive tract of humans and to examine expression of some xenobiotic-metabolizing cytochrome P450 enzymes (e.g. CYP1) in human uterus. Possible synergistic effects of environmental pollutants and their consequences in the reproductive organs will also be investigated. Cell types from the female reproductive tract are responsive to sex steroids and relatively readily available for culturing, which make them suitable for use in an in vitro-model for testing the effects of endocrine disruptors on human cells. We also use an in vitro model where effects of EDCs on early implantation can be studied.
This project is an integrated clinical and pre-clinical project which aims at clarifying the biochemical association between endometriosis and subfertility/infertility, endometriosis related pain as well with endometrial angiogenesis. It is known that women with endometriosis suffer from fertility problems that not necessarily are related with anatomical changes due to pelvic adhesions but to an abnormal biochemical pelvic environment. It is also known that the extent of endometriosis does not relate to pain. We are currently investigating the importance of several biochemical parameters for the questions raised. A better understanding of how normal endometrial angiogenesis is regulated also forms basis for further work studying the possible involvement of a disturbed angiogenesis in the dysfunctional endometrium (bleeding disturbances, endometrial infertility, etc). Such knowledge might also give insights in how endometrial angiogenesis can be controlled, for instance the potential usefulness of angiogenesis inhibitors for contraception. A better understanding of the relationship between the mitotic activity in endometriotic lesions, pain, angiogenic activity and potential serum markers could lead to better diagnostic methods than those currently used and also new treatment strategies of endometriosis. We are also investigating some new strategies to treat deep endometriotic lesions.
Cervical cancer is the second most frequent cancer among women worldwide and caused by persistent infection by oncogenic types of human papillomavirus (HPV). The organised gynaecological screening in Sweden has reduced the incidence of cervical cancer by 50%. A further reduction may be achieved by introducing HPV typing as a primary test and a screening system where women can take the samples at home at their own convenience and thereby increase the population coverage. At present there is a lack of studies using repeat HPV testing and self-collected samples in primary screening. The purpose of this project is to perform a randomised study and some studies associated with the sensitivity and specificity of self-sampling for HPV analysis.
This is an integrated experimental and clinical project where the pathophysiology of PE is in focus. We are comparing early and late onset PE by studying inflammation, angiogenesis and some other groups of markers. We also have a project where we will study the association between previous pre-eclampsia and cardiovascular disease later in life, in a cohort of 75 year old ladies, as a part of the PIVUS-study. Further, we have new project where we will use magnetic resonance spectroscopy to study placental perfusion and metabolism in pregnant women with and without pre-eclampsia. The project also includes a new animal model where we have studied the impact of antioxidants on the risk to develop PE.
FoSSH (Follow up after treatment of cervical dysplasia with Self-Sampling of HPV)
Efter behandling av cellförändringar i livmoderhalsen har ca 8% (4-18%) av kvinnorna kvarvarande förändringar eller får återfall inom två år. Dessa individer är viktiga att upptäcka eftersom de löper ökad risk för utveckling av livmoderhalscancer, och de kan behöva kompletterande behandling. Som kontroll efter behandling utförs i nuläget en cellprovtagning av barnmorska eller gynekolog efter ungefär sex månader. Man analyserar både celler och HPV i samma prov (”dubbelanalys”). Den aktuella studien (FoSSH) syftar till att undersöka om det räcker med enbart HPV-analys som uppföljning efter behandling, för att förutsäga risken för kvarvarande cellförändringar eller tidiga återfall. Provtagningen i studien utförs med självprovtagning, vid tre respektive sex månader efter behandling.
Reproductive medicine includes diagnosis and treatment of infertility and how to prevent infertility problems. Approximately 10 – 15 % of all couples of fertile age suffer from infertility. However, only around 50 % of those can be helped by assisted reproduction. We study different factors that could explain unexplained infertility. Development of new methodology for treatment of the early embryo as well as hormonal influence on the endometrium (the inner lining of the uterus) is of importance. Understanding on the human implantation process, how the communication between the fertilized oocyte and the endometrium occur, is a key process in future possibilities to treat infertility. The aim of our research, which is conducted both using advanced molecular biology methods and clinical applications is to improve treatment of infertility.
Our research projects
Implantation is only possible if the fertilized oocyte and the endometrium develop synchronously and optimal. To study this process, we use cell culture models and bioinformatics to study the communication between the early embryo and the endometrium.
Prostasomes are exosomes from the prostate gland. They can transfer genetic material from to the oocyte during fertilization and they can also affect the endometrium. We study if they are of importance for the implantation process. The aim is to improve treatment of infertility in the future.
Normal fertilization occurs in the Fallopian tube and the fertilized oocyte is transported through the tube to the uterus to implant into the endometrium. Our research group studies the communication between the fertilized oocyte and the Fallopian tube for development of improved culture media.
Hormonal regulation of the endometrium
The endometrium develops each month to receive a fertilized oocyte. If there is no fertilization, the endometrium will be removed as a menstrual bleeding. Genetic factors, hormonal disease such as thyreoiditis, hormonal treatment and other factors such as growth factors influences the development of the endometrium. Our group has shown that the endometrium is different in many women suffering from unexplained infertility. We have also shown that hormone during fertility treatment might affect the endometrium negatively. Our studies aim at increase the knowledge on endometrial receptivity to improve diagnosis and treatment of infertility.
There is a lack of explanation for recurrent pregnancy loss, as knowledge of underlying mechanisms is unknown. Our studies aim at mapping factors that could be of importance for recurrent pregnancy loss. Furthermore, we are studying factors related to experiences of miscarriage.