The Center for Women's Reproductive Sciences Research targets five different areas of investigation in Reproductive Biology and includes not only OBGYN/Reproductive Scientists at Washington University but also outstanding multidisciplinary reproductive scientists who are joint faculty members in our department. Research efforts among this group can be divided into five thematic categories. These categories are:
- Molecular Reproductive Endocrinology (Drs. Boime, Schedl and Moley)
- Biology of Maternal-Fetal Interactions (Dr. Nelson )
- Gynecologic Oncology (Drs. Goodfellow and Mutch)
- Immunobiology of Pregnancy (Dr. Riley)
- Bladder epithelial biology (Dr. Mysorekar)
Summary of the Molecular Reproductive Endocrinology Section
Pregnancy success depends on the coordination of oocyte quality, embryo development, implantation and the correct synthesis and processing of placental and pituitary gonadotropins. The strength of this Section rests in the availability of training in all these areas. As evident from Dr. Moley's publications and training track record, Dr. Moley and her group made significant contributions in understanding effects of maternal diabetes on oocyte and embryonic developments over the years. Dr. Schedl is an expert in germ cell proliferation and entry into meiosis,progression through meiotic prophase,meiotic maturation, and ovulation germline sex determination. Drs. Moley and Schedl's research groups work closely via joint lab meetings sharing research ideas and various technical approaches.
The cell biology of glycoprotein processing and cell trafficking is key to their functional activity. Similarly, glucose transporter biology and trafficking of these proteins also plays an important function in the expression and function of these transporters in the early embryo. This program section will use the combined expertise of Drs. Moley and Boime to investigate intracellular trafficking of these reproduction-associated proteins using polarized cell models, chimera studies and genetic models. Trainees will have the opportunity to explore the molecular basis for these cellular processes and how they relate to reproductive systems.
Summary of the Biology of Maternal-Fetal Interactions Section
Preterm labor reflects a dysregulation of the normal Maternal-Fetal Interaction and preterm delivery remains one of the most common pregnancy related problems and is the leading cause of infant morbidity and mortality in this country. This program area will use the combined expertise of Dr. Nelson to investigate the mechanisms of this condition. Trainees will have the opportunity to explore the molecular basis of parturtion using genetically modified mice and Dr. Nelson's expertise in the area of human uterine contractility. The Nelson laboratories have made significant contributions alone and jointly in defining the role uterine prostaglandin endoperoxide synthase-2 (COX-2) in preterm labor.
Intrauterine growth retardation is another significant pathophysiological state that is directly related to poor Maternal-fetal interactions and specifically to abnormalities in trophoblast development. Similarly, preeclampsia, one of the leading causes of maternal mortality in this country, is also thought to be due to aberrant trophoblast differentiation. This program area will use the experience of Dr. Nelson to investigate the mechanism of normal and abnormal trophoblast differentiation and how maternal health or disease affects this developmental process. The trainee will have the opportunity to investigate the molecular basis of this process using models of villous hypoxia, underperfusion and relate these directly to human diseased placentae. The Nelson laboratories have made substantial contributions alone and collaboratively in defining maternal-fetal interactions in competitive histomorphology, cell signaling and gene regulation studies.
Summary of the Gynecologic Oncology Section
Endometrial cancer is the most common gynecologic malignancy in the United States, with over 36,000 new cases diagnosed each year. Two major risk factors for the development of endometrial hyperplasia and carcinoma have been identified, one of which is genetic and the other environmental. An inherited defect in DNA mismatch repair confers a approximately 50% lifetime risk for the development of endometrial carcinoma. In addition, somatic (acquired) defects in mismatch repair are frequent in endometrial cancer, further emphasizing the importance of loss of DNA mismatch repair in these tumors. In addition, cervical cancer kills more than 200,000 people each year worldwide, disproportionately affecting women of low socioeconomic status. Infection with high-risk human papillomavirus (HPV) is the main causal factor, but additional factors must be involved because only a small proportion of HPV-infected women develop cancer. Epidemiologic studies suggest that some predisposing factors are genetic heritability and these factors account for about 27 percent of the total variation in development to cervical cancer. This program area uses the combined expertise of Drs. Goodfellow and Mutch to investigate genetic susceptibility genes, diagnostic molecular markers, prognostic biological markers and DNA mismatch repair in these two highly prevalence gynecologic malignancies. Trainees will have the unique opportunity to combine molecular and genetic mechanisms with translational studies to address new hypotheses using human normal and cancerous tissue. These investigators have a solid track record in recruiting and training postdoctoral fellows.