1. Regular Use of Depot Medroxyprogesterone Acetate Causes Thinning of the Superficial Lining and Apical Distribution of Human Immunodeficiency Virus Target Cells in the Human Ectocervix
- Author
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Maria Röhl, Kristina Broliden, Frideborg Bradley, Kenneth Omollo, Behnaz Khalilzadeh-Binicy, Alexandra Åhlberg, Julius Oyugi, Carolina Wählby, Joshua Kimani, Gabriella Edfeldt, Keith R. Fowke, Mathias Mack, Annelie Tjernlund, and Julie Lajoie
- Subjects
0301 basic medicine ,Infectious Medicine ,Langerin ,Ectocervix ,Physiology ,Infektionsmedicin ,HIV Infections ,Cervix Uteri ,Medroxyprogesterone Acetate ,progesterone ,HIV target cells ,Microbiology in the medical area ,03 medical and health sciences ,Basal (phylogenetics) ,0302 clinical medicine ,estradiol ,female genital mucosa ,Mikrobiologi inom det medicinska området ,Contraceptive Agents, Female ,medicine ,digital image analysis ,Humans ,Immunology and Allergy ,Medroxyprogesterone acetate ,Distribution (pharmacology) ,Sex organ ,030219 obstetrics & reproductive medicine ,biology ,business.industry ,hormonal contraception ,HIV ,in situ staining ,3. Good health ,DMPA ,030104 developmental biology ,Infectious Diseases ,Hormonal contraception ,biology.protein ,epithelial integrity ,Female ,business ,Hormone ,medicine.drug - Abstract
Background The hormonal contraceptive depot medroxyprogesterone acetate (DMPA) may be associated with an increased risk of acquiring human immunodeficiency virus (HIV). We hypothesize that DMPA use influences the ectocervical tissue architecture and HIV target cell localization. Methods Quantitative image analysis workflows were developed to assess ectocervical tissue samples collected from DMPA users and control subjects not using hormonal contraception. Results Compared to controls, the DMPA group exhibited a significantly thinner apical ectocervical epithelial layer and a higher proportion of CD4+CCR5+ cells with a more superficial location. This localization corresponded to an area with a nonintact E-cadherin net structure. CD4+Langerin+ cells were also more superficially located in the DMPA group, although fewer in number compared to the controls. Natural plasma progesterone levels did not correlate with any of these parameters, whereas estradiol levels were positively correlated with E-cadherin expression and a more basal location for HIV target cells of the control group. Conclusions DMPA users have a less robust epithelial layer and a more apical distribution of HIV target cells in the human ectocervix, which could confer a higher risk of HIV infection. Our results highlight the importance of assessing intact genital tissue samples to gain insights into HIV susceptibility factors.
- Published
- 2020