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

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...

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Published inClinical immunology (Orlando, Fla.) Vol. 255; p. 109750
Main Authors Gupta, Prachi Mehrotra, Balle, Christina, Tharp, Gregory K., Nelson, Sydney A., Gasper, Melanie A., Brown, Bryan, Alisoltani, Arghavan, Onono, Maricianah, Palanee-Phillips, Thesla, Nair, Gonsagrie, Ayele, Hosseana, Noel-Romas, Laura, Passmore, Jo-Ann S., Burgener, Adam D., Heffron, Renee, Jaspan, Heather B., Bosinger, Steven E.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.10.2023
Academic Press
Subjects
Contraception
Contraceptive Agents
Copper
Female
Female genital tract
Humans
Intrauterine Devices, Copper
Levonorgestrel - pharmacology
Mucosa
Pregnancy
Randomized clinical trial
Reproductive health
Systems Analysis
Transcriptome
Reproductive health
Contraception
Randomized clinical trial
Mucosa
Female genital tract
Transcriptome
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Summary: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. [Display omitted] •Contraceptives significantly impact the immune system of the female genital tract (FGT)•The impact of DMPA, LNG implant, and Cu-IUD on the FGT was studied in 188 women from the ECHO trial using functional genomics•Cu-IUD led to elevated metallothionein responses associated with increased inflammation•DMPA usage was associated with enhanced T cell recruitment and signaling•LNG implant had the mildest impact on the FGT environment
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These authors contributed equally to this work.
Current address: Heersink School of Medicine, University of Alabama.
ISSN:1521-6616
1521-7035
DOI:10.1016/j.clim.2023.109750