Tubal factor infertility (TFI) is caused by obstruction of the female genital tract and is responsible for 30% of the infertility found in women. Multiple infections with Chlamydia trachomatis leads to tubal pathologies including extensive tubal scarring, chronic salpingitis, distal tubal obstruction, pelvic inflammatory disease and ectopic pregnancy. Traditionally, the diagnosis of TFI is done through highly invasive methods such as hysterosalpingography and transvaginal salpingoscopy. In addition, there is no approved non-invasive clinical method for diagnosing the risk of developing TFI. Looking forward, there is a critical need for a noninvasive biomarker for TFI that could be used in therapy prediction and disease surveillance. The objective of this project is to identify novel and differentially expressd miRNA and genes regulated in CT pathogenesis that can predict the risk of developing TFI. miRNAs are fast emerging as diagnostic markers of other infectious diseases and cancer and they have been reported to regulate female reproductive tract development. We recently reported that miRNA was dysregulated in a murine model of Chlamydia-induced TFI. In this study we plan to identify novel and differentially expressed miRNA linked to the pathogenesis of Chlamydial infection leading to TFI. We also plan to identify genes whose expressions are strongly regulated by Chlamydia infection and are associated with TFI. The molecular signatures that will be acquired from this study are expected to provide a pathway to future design of a diagnostic marker for TFI. This study is expected to have a positive impact on the reproductive health of women and children by reducing the impact of TFI.

Public Health Relevance

Tubal factor infertility (TFI) represents 36% of female infertility, and is an important public health problem. Finding a biomarker for the risk of developing TFI caused by sexually-transmitted diseases is of public health significance, and the use of miRNA as a biomarker will be a novel and sought after method for the prediction of risk of developing TFI.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Pilot Research Project (SC2)
Project #
5SC2HD086066-02
Application #
9097728
Study Section
Special Emphasis Panel (ZGM1)
Program Officer
Eisenberg, Esther
Project Start
2015-06-24
Project End
2018-04-30
Budget Start
2016-06-01
Budget End
2017-04-30
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Morehouse School of Medicine
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
102005451
City
Atlanta
State
GA
Country
United States
Zip Code
30310
Igietseme, Joseph U; Omosun, Yusuf; Nagy, Tamas et al. (2018) Molecular Pathogenesis of Chlamydia Disease Complications: Epithelial-Mesenchymal Transition and Fibrosis. Infect Immun 86:
Ryans, Khamia; Omosun, Yusuf; McKeithen, Danielle N et al. (2017) The immunoregulatory role of alpha enolase in dendritic cell function during Chlamydia infection. BMC Immunol 18:27