Progestin-Containing Contraceptives Alter Expression of Host Defense-Related Genes of the Endometrium and Cervix

Abstract

Epidemiological studies indicate that progestin-containing contraceptives increase susceptibility to HIV, although the underlying mechanisms involving the upper female reproductive tract are undefined. To determine the effects of depot medroxyprogesterone acetate (DMPA) and the levonorgestrel intrauterine system (LNG-IUS) on gene expression and physiology of human endometrial and cervical transformation zone (TZ), microarray analyses were performed on whole tissue biopsies. In endometrium, activated pathways included leukocyte chemotaxis, attachment, and inflammation in DMPA and LNG-IUS users, and individual genes included pattern recognition receptors, complement components, and other immune mediators. In cervical TZ, progestin treatment altered expression of tissue remodeling and viability but not immune function genes. Together, these results indicate that progestins influence expression of immune-related genes in endometrium relevant to local recruitment of HIV target cells with potential to increase susceptibility and underscore the importance of the upper reproductive tract when assessing the safety of contraceptive products.

Keywords: cervix; endometrium; gene expression; host defense; progestin-based contraceptives.

Figure 1.

Principal component analysis.

Figure 2.

Hierarchical clustering.

Figure 3.

Venn diagrams.

Figure 4.

Summary and implications of pathways regulated by progestins in endometrium and transformation zone (TZ).