Request for Funding

Medical Student Research Fellowship for Summer 2004

Mentor: Mala Mahendroo
Department: Obstetrics and Gynecology
Room number:F2.306
Mail Code:9032
Phone number:214 648 3091
E-mail:mala.mahendroo@utsouthwestern.edu
Project title: Investigations into the Role of Tight Junction Proteins in Cervical Ripening

Human subjects IRB approved project number (where applicable):

Animal subjects IRB approved project number (where applicable): 0906-03-02-1

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)
This is a basic research project with minimal animal use.
Brief Description of Project:
Parturition, the process of birth, is an essential biological function for which the molecular mechanisms are poorly understood. Normal parturition requires a coordinately contracting uterus and a cervix that undergoes extensive remodeling and dilatation to allow passage of the fetus through the birth canal. Our laboratory is interested in defining the molecular mechanisms that control cervical ripening by using mouse models that include mice with defects in cervical ripening.
Movement of molecules from the blood into the lumen via the intracellular route is restricted by resistance of the tight junction complex. Tight junctions are integral membrane proteins that are thought to function as a primary barrier to the diffusion of solutes through the paracellular pathway. A family of proteins termed claudins, have been identified as a component of tight junctions. Increased expression of claudin proteins results in an increased number of tight junction and a decrease in secretions via the paracellular pathway. The expression of claudins in the pregnant cervix is unkown.
Cervical ripening is characterized by an increase in secretions by the cervical epithelia. We propose that in normal cervical ripening there is an increase in paracellular transport at the end of pregnancy that results in increased cervical secretions, a decrease in the number of tight junctions and decreased expression of tight junction proteins. In the proposed study, the role of claudins in regulation of cervical paracellular permeability will be tested by screening for tight junction mRNAs expressed in the pregnant mouse cervix, determining their pattern of expression through pregnancy and visualizing changes in tight junction numbers by electron microscopy. These studies will provide novel insights into the molecular mechanisms that regulate cervical ripening.

Previous Research Activities or Publications with Medical Students:
None

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