Systems analysis reveals differential expression of endocervical genes in African women randomized to DMPA-IM, LNG implant or cu-IUD

• Type of Material: Article
• Authors: Prachi Mehrotra Gupta, affiliation; Christina Balle, University of Cape Town; Gregory K. Tharp, Emory University; Sydney Nelson, Emory University; Melanie A. Gasper, Seattle Children's Research Institute; Bryan Brown, University of Washington, Seattle; Arghavan Alisoltani, Northwestern University; Maricianah Onono, Kenya Medical Research Institute; Thesla Palanee-Phillips, University of Witwatersrand; Gonsagrie Nair, Desmond Tutu HIV Centre; Hosseana Ayele, Case Western Reserve University; Laura Noel-Romas, Case Western Reserve University; Jo-Ann S. Passmore, University of Cape Town; Adam D. Burgener, Case Western Reserve University; Renee Heffrom, University of Washington, Seattle; Heather B. Jaspan, University of Cape Town; Steven Bosinger, Emory University
• Language: English
• Date: 2023-10
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Authors. Published by Elsevier Inc.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1016/j.clim.2023.109750
• Title of Journal or Parent Work: Clinical Immunology
• Volume: 255
• Start Page: 109750
• Grant/Funding Information: This work and the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Study were made possible by the combined generous support of the Bill & Melinda Gates Foundation (Grant OPP1032115), the American people through the United States Agency for International Development (Grant AID-OAA-A-15–00045), the Swedish International Development Cooperation Agency (Grant 2017/762965–0), the South Africa Medical Research Council, and the United Nations Population Fund. Contraceptive supplies were donated by the Government of South Africa and US Agency for International Development. Funding to support this ancillary study of biological mechanisms was from the US National Institute of Child Health and Human Development R01 HD089831 to RH and HBJ. CB was supported by bursary funds from the Poliomyelitis Research Foundation (fund number 17/43) during her Ph.D. work. RNA Sequencing was conducted in the ENPRC Genomics Core which receives support from NIH grants P51OD011132 and S10OD026799.
• Keywords: Transcriptome; Female genital tract; Mucosa; Randomized clinical trial; Reproductive health; Contraception
• Research Categories: Health Sciences, Immunology; Health Sciences, Obstetrics and Gynecology

Abstract

Although effective contraceptives are crucial for preventing unintended pregnancies, evidence suggests that their use may perturb the female genital tract (FGT). A comparative analysis of the effects of the most common contraceptives on the FGT have not been evaluated in a randomized clinical trial setting. Here, we evaluated the effect of three long-acting contraceptive methods: depot medroxyprogesterone acetate(DMPA-IM), levonorgestrel(LNG) implant, and a copper intrauterine device (Cu-IUD), on the endocervical host transcriptome in 188 women from the Evidence for Contraceptive Options and HIV Outcomes Trial (ECHO) trial. Cu-IUD usage showed the most extensive transcriptomic changes, and was associated with inflammatory and anti-viral host responses. DMPA-IM usage was enriched for pathways associated with T cell responses. LNG implant had the mildest effect on endocervical gene expression, and was associated with growth factor signaling. These data provide a mechanistic basis for the diverse influence that varying contraceptives have on the FGT.