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Molecular mechanisms of PCOS-induced fetal loss
Sweden (IFMSA-Sweden) - Goteborgs Universitet, Gothenburg
Department of Physiology and Endocrinology
Linus R Shao
Linus R Shao
Type of Research Project
- Clinical Project with Laboratory work
What is the background of the project?
Polycystic ovary syndrome (PCOS) affects 4%–21% of all adolescent and reproductive-aged women depending on the criteria used to define PCOS and on the ethnicity of the group being studied. PCOS manifests as a range of endocrine and reproductive aberrations rather than as a well-deﬁned etiological entity. Several lines of evidence from clinical studies indicate that PCOS patients frequently present with adverse reproductive outcomes, including miscarriage, regardless of whether conception occurs spontaneously or through in vitro fertilization techniques. However, elevated rates of miscarriage in pregnant PCOS patients have not been properly addressed due to the inability to study the effects of hyperandrogenism and insulin resistance on the initiation or progression of miscarriage in healthy women during pregnancy. Pre-clincial and clincal observations have highlighted the disrupted balance between ROS production and antioxidant capacity in PCOS patients and in different animal models. However, how aberrant ROS accumulation and related cellular and molecular signaling events account for fetal loss under PCOS conditions has remained elusive.
What is the aim of the project?
Our studies will document the molecular events that are altered in the uterine and placental of pregnant rats exposed to high androgen levels, using the non-aromatizable androgen DHT, and/or insulin.
What techniques and methods are used?
The techniques and methods that will be used are; morphological assessment, quantitative Reverse Transcription Polymers Chain Reaction (qRT-PCR) to detect and quantify nucleic acids, Western blot (where the proteins will first be denatured and then gel electrophoresis follows where a electrophoresis membrane is washed with a solution containing antibodies, a method to detect protein levels) immunostaining and imaging (to be able to visualise the antibodies) and then Transmission electron microscopy (which is a microscopy technique), and enzyme-linked immunosorbent assay (ELISA) to detect the proteins. One paper was published and anotherone is on the way.
What is the role of the student?
- The student will mainly observe
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
It is expected that the students will read the related articles and that they will participate in the lab work, under supervision. As I mentioned above, the lab work will be done with the methods; morphological assessment, immunostaining and imaging, Transmission electron microscopy, Western blot, quantitative Reverse Transcription Polymers Chain Reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA.) They will also discuss with superiors and project team members a long the way what is being done as they will not perform all of these techniques by themselves. Instead they will be done under supervision and work with the methods (with the help from superiors) as the research proceeds.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Approximately 5 hours / week by supervisor and postdoc in the research group.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
They will have to be MD students.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months)
- Hyperandrogenism and insulin resistance induce gravid uterine defects in association with mitochondrial dysfunction and aberrant ROS production. Hu M; Zhang Y; Guo X. Am J Physiol Endocrinol Metab. 2019 Mar 12. doi: 10.1152/ajpendo.00359.2018 (https://www.ncbi.nlm.nih.gov/pubmed/30860876)
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