Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effects of Injectable DMPA and Combined Oral Contraceptive Use on HIV Susceptibility Factors in Pig-tailed Macaques

ABSTRACT: Progestin-based contraception may increase the risk of vaginal HIV acquisition to a level greater than the progesterone-rich luteal phase of the menstrual cycle, which has been demonstrated to have a significantly higher transmission rate compared to the follicular phase. We used pig-tailed macaque (Macaca nemestrina) model to evaluate the effects of administration of the oral the combined oral contraceptives (COCs) depot medroxyprogesterone acetate (DMPA) and levonorgestrel (LNG) on mucosal factors that influence HIV susceptibility. We compared the pH and vaginal epithelial thickness data from previous studies, and evaluated contraception-induced molecular changes in the vagina using transcriptional and cytokine profiling. The administration of DMPA caused a pronounced thinning of the vaginal epilthelium relative to measurements takein in the follicular or luteal phase. DMPA also induced a significant increase in vaginal IL10 expression. Lastly, using RNA-Seq analyses of vaginal biopsies, we noted that both DMPA- and LNG-based contraception induced a signature of gene expression similar to that of the luteal phase, only more exacerbated, and including widespread down-regulation of HIV-restriction genes. Use of progestin-based contraception might engender a milieu that poses an increased risk of HIV transmission than that of the luteal phase via vaginal thinning, induction of immunosuppressive cytokines, and widespread suppression of HIV restriction factors.

ORGANISM(S): Macaca mulatta Macaca nemestrina

PROVIDER: GSE99800 | GEO | 2020/06/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Progestin-containing Contraceptives Alter Expression of Host Defense-related Genes of the Endometrium and Cervix

Project description:Epidemiological studies indicate that progestin-containing contraceptives may increase susceptibility to HIV and other infections; however, 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 the 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 (z>2.5) and LNG-IUS (z>3.5) users, and regulation of pattern recognition receptors and other immune mediators. In cervical TZ, progestin treatment altered expression of tissue remodeling and viability genes, but not those of immune functions. Together, these results indicate that progestins influence expression of immune-related genes in endometrium that would be expected to result in the local recruitment of HIV target cells, and thus may increase HIV susceptibility. It is important to consider the upper reproductive tract in the assessment of effects of contraceptives that may influence susceptibility to pathogens, such as HIV. Cross-sectional study conducted at an academic medical center. Cervical transformation zone and endometrial biopsies were obtained from 3 groups of volunteers: those using no hormonal contraceptives (controls, mid-secretory phase, n=20 cervix, 11 endometrium), DMPA users (150mg, n=15, 8), or LNG-IUS users (n=17, 13). DMPA and LNG-IUS groups had used these contraceptives for at least 6 months.

2014-11-21 | E-GEOD-60129 | biostudies-arrayexpress

Cataloguing of Potential HIV Susceptibility Factors during the Menstrual Cycle of Pigtail Macaques

Project description:Our earlier studies in pig-tailed macaques demonstrated varying SHIV susceptibility during the menstrual cycle, likely caused by cyclic variations in immune responses in the female genital tract. There is concern that high-dose, long-lasting, injectable progestin-based contraception could mimic the luteal phase and predispose women to HIV-1 acquisition and transmission. In this study, we adopted a systems biology approach employing proteomics (tandem mass spectrometry), transcriptomics (RNA microarray hybridization), and other specific protein assays (enzyme-linked immunosorbent assays and multiplex chemokine-cytokine measurements) to characterize the effects of hormonal changes on the expression of innate factors and secreted proteins in the macaque vagina. Several antiviral factors and pathways (including acute phase response signaling and complement system) were overexpressed in the follicular phase. Conversely, during the luteal phase there were factors overexpressed (including moesins, syndecans, integrins, among others) that could play direct or indirect roles in enhancing HIV-1 infection. Thus, our study showed that specific pathways and proteins/genes might be working in tandem to regulate innate immunity, thus fostering further investigation and future design of approaches to help counter HIV-1 acquisition in the female genital tract. Samples were hybridized to Affymetrix GeneChip® Rhesus Macaque Genome Arrays. Vaginal pinch biopsies were collected from 12 pig-tailed macaques at both the follicular and luteal phases. The data from one animal suggested low RNA quality and was excluded.

2015-07-08 | E-GEOD-68079 | biostudies-arrayexpress

Progestin-containing Contraceptives Alter Expression of Host Defense-related Genes of the Endometrium and Cervix

2014-11-21 | GSE60129 | GEO

Cataloguing of Potential HIV Susceptibility Factors during the Menstrual Cycle of Pigtail Macaques

2015-07-08 | GSE68079 | GEO

Genes linked to cervicovaginal integrity are dysregulated in DMPA but not COC contraception users

Project description:Injectable depot medroxyprogesterone acetate (DMPA) is one of the most popular contraception methods in areas of high HIV seroprevalence. Evidence is accumulating that use of DMPA might be associated with an increased risk of acquiring HIV-1; however, mechanisms of this association are not completely understood. We conducted a comparative whole genome transcriptome profiling of human ectocervical tissues before and after use of two hormonal contraception methods: injectable DMPA and not linked to increased risk of HIV acquisition combined oral contraceptive (COC). Microarray analysis identified 235 ectocervical genes altered in the DMPA users. The most striking effect of DMPA, but not COC, was a strong dysregulation of genes strategically involved in the maintenance of epithelial barrier function; the alterations were most likely due to the DMPA-induced estrogen deficiency. We also demonstrated inter-individual heterogeneity in gene expression profiles of the DMPA users that clustered into distinct groups. The differential response may explain divergence in reports on effects of DMPA use. We propose that impairment of the cervicovaginal epithelial integrity in response to DMPA administration is the major mechanism underlying a potential increased risk of HIV-1 acquisition in DMPA users.

2018-04-10 | GSE110313 | GEO

Transcriptome-wide impact of season and progesterone in the medio-basal hypothalamus of the goat

Project description:Here we used RNAseq to compare the transcriptomes of the medio-basal hypothalamus of goats killed at two different times of the year (end of January and mid-May) and under different hormonal conditions (follicular and luteal phase, in January only). The current experiment was designed to identify the impact of photoperiod upon the transcriptome and to compare it with that of the ewe. The current design also tested the potential impact of progesterone (P4) upon this transcriptome; ewes were treated with a vaginal fluogestone acetate sponge during the breeding season (January) and killed either 2 days (follicular phase) or 8 days (luteal phase) after estrumate treatment and sponge removal.

2022-05-12 | GSE202507 | GEO

Impact of the menstrual cycle and ethinyl estradiol/etonogestrel contraceptive vaginal ring on granulysin and other mucosal immune mediators

Project description:We conducted a prospective, open-label study to determine the effect of the NuvaRing on gene expression in the endocervix and immune-related protein expression in cervicovaginal secretions. Women provided endocervical cytobrush samples during the luteal and follicular phases of the menstrual cycle (as determined by progesterone levels) as well as during NuvaRing use. Gene expression was measured using Illumina Human HT12 v4 BeadChip microarrays. We compared the NuvaRing visit to each phase of the menstrual cycle separately, as well as follicular and luteal phase samples to each other, adjusting for technical batch, presence of blood in vaginal discharge, and BV status by Nugent score, and blocking on participant. We found that gene expression in the endocervical canal changed across the menstrual cycle and in response to NuvaRing use. In particular, we observed a continuum of expression of immune-related genes and gene sets in the endocervical canal: highest during NuvaRing use, intermediate in the follicular phase, and lowest in the luteal phase.

2020-12-30 | GSE142058 | GEO

Transcriptome-wide impact of progesterone in the medio-basal hypothalamus of the ewe

Project description:Here we used RNAseq to assess the impact of progesterone (P4) on the transcriptome of the medio-basal hypothalamus of ewes. Ewes were treated with a vaginal fluogestone acetate sponge in mid-February. The sponge was removed in early March and ewes received a PMSG injection. Animals were then killed either 2 days (follicular phase) or 12 days (luteal phase) later.

2022-05-12 | GSE202508 | GEO

Illumina sequencing of vaginal epithelial cells from women using depot medroxyprogesterone acetate or non-hormonal contraception

Project description:The use of the hormonal contraceptive DMPA has been associated with a moderate increase in sexually transmitted infections, including HIV-1. To better understand the biological mechanisms behind this phenomenon, we report here the use of mRNA-sequencing on the Illumina HiSeq2000 of vaginal epithelial cells from women using DMPA or controls. We found that women using DMPA demonstrate over 330-fold decrease in the anti-microbial peptide human beta defensin 3 (HBD3) and massive downregulation of genes involved in structural integrity, barrier function, and wound healing. CXCL6, CXCL1, and IL-1B among other inflammatory genes were up-regulated in the tissue of DMPA users compared to controls. Overall, these results demonstrate significant differences in basic epithelial functions following DMPA use.

2016-04-23 | GSE68229 | GEO

The Human Oviductal Transcriptome Reveals An Anti-inflammatory, Anti-angiogenic, Secretory and Matrix-stable Environment During Embryo Transit

Project description:Human oviduct serves as a conduit for sperm in the peri-ovulatory phase and to nurture and facilitate transport of the developing embryo en route to the uterus for subsequent nidation during the luteal phase of the cycle. Interactions between the embryo and oviductal epithelial surface proteins and secreted products during the four day embryo transit are largely undefined. Herein, we have investigated gene expression in human oviduct in the early luteal vs. follicular phase to identify candidate genes and biomolecular processes that may participate in maturation and transport of the embryo as it traverses this tissue. Oviductal RNA was isolated, processed, and hybridized to oligonucleotide arrays. Resulting data were analyzed by bioinformatic approaches and revealed that 650 genes were significantly downregulated and 683 genes were significantly upregulated in the luteal vs. follicular phase. Real-time RT-PCR, immunoblot analysis, and immunohistochemistry confirmed select gene expression and cellular protein localization. The data demonstrate downregulation of genes involved in macrophage recruitment, immunomodulation, and matrix-degeneration and upregulation of ion transport and secretions as well as anti-angiogenic and early pregnancy recognition genes in luteal vs. follicular phase oviduct. Together, these data suggest a unique hormonally regulated environment during embryo development, maturation and transport through human oviduct. We have investigated gene expression in human oviduct in the early luteal vs. follicular phase. Oviductal RNA was isolated, processed, and hybridized to oligonucleotide arrays. Resulting data were analyzed by bioinformatic approaches and revealed that 650 genes were significantly downregulated and 683 genes were significantly upregulated in the luteal vs. follicular phase. Real-time RT-PCR, immunoblot analysis, and immunohistochemistry confirmed select gene expression and cellular protein localization.

2013-08-30 | E-GEOD-33805 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data