Gene Profiling of Endocervical Tissues during the Menstrual Cycle

Presentation Number: SUN-0044
Date of Presentation: June 22nd, 2014

Sevim Yildiz Arslan*, Yanni Yu, Thomas H. Hope and Julie Kim
Northwestern University, Chicago, IL

Abstract

Hormone fluctuation throughout the menstrual cycle contributes to changes in immune responses that render the upper female reproductive tract vulnerable to HIV infection. It is thought that HIV infection is more likely to occur during luteal phase because of dampening of protective immune responses. As it is becoming more evident that hormone production as well as function of immune cells are ideal candidates for HIV transmission, it is essential to understand the role of hormones on HIV infection in women. The objective of this study is to identify genes in endocervical tissues of women that are differentially expressed in the follicular versus the luteal phases of the menstrual cycle using gene expression profiling. Cervical tissue samples of different hormonal status were obtained from routine hysterectomies. A microarray using the IIlumina platform was performed with 8 tissues from follicular and 8 tissues from luteal phases of the menstrual cycle. Data analysis revealed 450 genes significantly different between the two phases, with a p-value < 0.05 and a fold change cutoff of 1.5. Categorization of these genes, using Ingenuity Pathway Analysis, GeneGo as well as DAVID revealed genes associated with collagen fibril morphology, differentiation, proliferation, dendritic cell (DC) and leukocyte migration, among others. We focused on genes associated with dendritic cell maturation and migration as well as hormone regulation by assessing their differential expression using real time PCR as well as IHC staining to examine protein expression. Both mRNA expression and protein levels of genes, such as COL3A1, SLPI, DC-SIGN, and IL-10 that may play a role in HIV-DC interaction, were significantly decreased in luteal as compared to follicular phase (p < 0.05).

In the endocervix, mature CD83+ DCs outnumber immature CD1a+ DCs throughout the menstrual cycle. IHC studies showed that protein levels of CD83+ DCs decreased from follicular to the luteal phase, indicating a tolerogenic phenotype that may be regulated by sex hormones. Overall, this is the first microarray analysis comparing gene expression in endocervical tissues in cycling women. This study identifies key genes of HIV-DC interaction and potentially novel mechanisms influenced by ovarian hormones which will significantly enhance our understanding of HIV infection in women.

 

Nothing to Disclose: SY, YY, THH, JK