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

Prachi Mehrotra Gupta; Christina Balle; Gregory K Tharp; Sydney A Nelson; Melanie A Gasper; Bryan Brown; Arghavan Alisoltani; Maricianah Onono; Thesla Palanee-Phillips; Gonsagrie Nair; Hosseana Ayele; Laura Noel-Romas; Jo-Ann S Passmore; Adam D Burgener; Renee Heffron; Heather B Jaspan; Steven E Bosinger

doi:10.1016/j.clim.2023.109750

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

Clin Immunol. 2023 Oct:255:109750. doi: 10.1016/j.clim.2023.109750. Epub 2023 Sep 3.

Authors

Prachi Mehrotra Gupta¹, Christina Balle², Gregory K Tharp¹, Sydney A Nelson¹, Melanie A Gasper³, Bryan Brown⁴, Arghavan Alisoltani⁵, Maricianah Onono⁶, Thesla Palanee-Phillips⁷, Gonsagrie Nair⁸, Hosseana Ayele⁹, Laura Noel-Romas⁹, Jo-Ann S Passmore¹⁰, Adam D Burgener⁹, Renee Heffron¹¹, Heather B Jaspan¹², Steven E Bosinger¹³

Affiliations

¹ Emory National Primate Research Center (ENPRC) Genomics Core Laboratory, Division of Microbiology & Immunology, Emory University, Atlanta, GA, USA.
² Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.
³ Seattle Children's Research Institute, Seattle, WA, USA.
⁴ Seattle Children's Research Institute, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA.
⁵ Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁶ Kenya Medical Research Institute, Kisumu, Kenya.
⁷ Wits RHI, University of the Witwatersrand, Faculty of Health Sciences, School of Public Health, Johannesburg, South Africa; Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
⁸ Desmond Tutu HIV Centre, Cape Town, South Africa.
⁹ Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
¹⁰ Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa; National Health Laboratory Service, Cape Town, South Africa; CAPRISA DSI-NRF Centre of Excellence in HIV Prevention, University of Cape Town, South Africa.
¹¹ Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA.
¹² Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa; Seattle Children's Research Institute, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA.
¹³ Emory University School of Medicine, Department of Pathology & Laboratory Medicine, GA, USA; Emory Vaccine Center, Emory University, GA, USA. Electronic address: steven.bosinger@emory.edu.

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.

Keywords: Contraception; Female genital tract; Mucosa; Randomized clinical trial; Reproductive health; Transcriptome.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Contraceptive Agents
Copper*
Female
Humans
Intrauterine Devices, Copper*
Levonorgestrel / pharmacology
Pregnancy
Systems Analysis

Substances

Copper
Levonorgestrel
Contraceptive Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding