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Systems analysis of the female genital tract reveals differential expression of inflammatory and epithelial barrier genes in South African adolescents randomized to injectable, oral or vaginal ring contraception

ABSTRACT: Systems analysis of the female genital tract reveals differential expression of inflammatory and epithelial barrier genes in South African adolescents randomized to injectable, oral or vaginal ring contraception

PROVIDER: PRJNA721079 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14204000.fastq.gz	Fastqsanger.gz
	SRR14204001.fastq.gz	Fastqsanger.gz
	SRR14204002.fastq.gz	Fastqsanger.gz
	SRR14204003.fastq.gz	Fastqsanger.gz
	SRR14203904.fastq.gz	Fastqsanger.gz

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Systems analysis of the female genital tract reveals differential expression of inflammatory and epithelial barrier genes in South African adolescents randomized to injectable, oral or vaginal ring contraception

Project description:Use of hormonal contraceptives (HC) could alter the bacterial community, immune response and epithelial barrier integrity of the female genital tract (FGT) mucosal environment, leading to increased susceptibility to sexually transmitted infections (STIs), including HIV. Here, we tested whether use of three types of HCs, injectable Net-En, combined oral contraceptives (COC) and NuvaRing, a combined contraceptive vaginal ring (CCVR), led to distinct patterns in FGT host transcriptomics transcriptome in South African adolescent females. In an intention-to-treat analysis, we observed few changes in endocervical gene expression in the Net-En and COC groups. Relative to the COC and Net-En arms, samples from the CCVR arm had significant elevation of transcriptional networks driven by IL-6, IL-1 and NFKB, and lower expression of genes supporting epithelial barrier integrity. An integrated multivariate analysis of the cervicovaginal microbiome, transcriptome and cytokines demonstrated that networks of microbial dysbiosis and inflammation accurately discriminated the CCVR arm from the other contraceptive groups, while genes involved in epithelial cell differentiation were predictive of the Net-En and COC arms.

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Baseline gene transcription in genital fibroblasts

Project description:To gain insights into the role of androgen in genital morphogenesis, we compared basal transcriptional patterns in genital fibroblasts from 46,XY individuals with either wild-type AR or germline inactivation of the AR as a result of mutation. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Keywords: disease_state_design

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Genital fibroblasts of normal males and 46,XY females with androgen insensitivity syndrome

Project description:This SuperSeries is composed of the following subset Series: GSE3871: Effects of androgen treatment on genital fibroblasts GSE3872: Baseline gene transcription in genital fibroblasts Abstract: BACKGROUND: Androgen insensitivity syndrome (AIS) comprises a range of phenotypes from male infertility to complete feminization. Most individuals with AIS carry germline mutations of the androgen receptor (AR) that interfere with or ablate its function. As genital fibroblasts retain expression of the AR in vitro, we used genital skin fibroblasts from normal males and 46,XY females with complete AIS due to known AR mutations to gain insights into the role of the AR in human genital differentiation. RESULTS: Using DNA microarrays representing 32,968 different genes, we identified 404 transcripts with significant differences in transcription levels between genital skin fibroblasts cultured from normal and AIS-affected individuals. Gene-cluster analyses uncovered coordinated expression of genes involved in key processes of morphogenesis. On the basis of animal studies and human genetic syndromes, several of these genes are known to have specific roles in genital differentiation. Remarkably, genital fibroblasts from both normal and AIS-affected individuals showed no transcriptional response to dihydrotestosterone treatment despite expression of the AR. CONCLUSIONS: The results suggest that in addition to differences in the anatomic origin of the cells, androgen signaling during prenatal development contributes to setting long-lasting, androgen-independent transcriptional programs in genital fibroblasts. Our findings have broad implications in understanding the establishment and the stability of sexual dimorphism in human genital development. Refer to individual Series

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