Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1018671 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26104414_1.fastq.gz | Fastqsanger.gz | |||
| SRR26104415_1.fastq.gz | Fastqsanger.gz | |||
| SRR26104416_1.fastq.gz | Fastqsanger.gz | |||
| SRR26104417_1.fastq.gz | Fastqsanger.gz | |||
| SRR26104418_1.fastq.gz | Fastqsanger.gz |
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Project description:It is estimated that more than one million people in the United States identify as transgender. Despite recent increased visibility, transgender individuals remain marginalized and subject to health disparities, and are underrepresented in biomedical research. Our central hypothesis is that gender affirming hormone therapy in transgender men leads to a dysregulated innate immune microenvironment and impaired barrier function of the vaginal mucosal compartment. we will conduct transcriptomic studies to identify the gene expression profile of the testosterone dominant vagina to identify changes in the immunologic signaling pathways that could negatively impact host-pathogen interactions. We conducted transcriptomic studies using RNA sequencing to identify the gene expression profile of the testosterone dominant vagina in comparion to the estradiol dominant vagina and vaginal tissue without sex hormone exposure to identify changes in the immunologic signaling pathways that could negatively impact host-pathogen interactions in this compartment in transgender men.
2026-02-06 | GSE317796 | GEO
Project description:Many transgender men receiving long-term testosterone replacement therapy (TRT) have high serum levels of testosterone, compared to the low levels seen in cisgender women. Compared to other sex hormones such as estrogen and progesterone, the effects of testosterone on the mammary gland have been relatively understudied. Comparison of mammary glands from transgender men on TRT and cisgender women can reveal the poorly understood consequences of testosterone expression on mammary gland biology and the long-term effects of TRT on patient health and disease outcomes. In this study, we performed single-cell RNA sequencing of breast tissues from cisgender women and transgender men on TRT. We identified that the donors on TRT had a decreased expression of genes downstream of estrogen signaling pathways in hormone receptor positive luminal epithelial, as well as a decrease in luteal phase gene activity in these donors. We confirmed this finding experimentally by showing reduced expression of progesterone receptor a/b, a prominent marker of estrogen signaling, in donors on TRT. Our results support the hypothesis that high levels of testosterone in transgender men on TRT suppresses hormone signaling in the breast through their impact on hormone receptor positive (HR+) mammary epithelial cells, with implications for TRT as an antagonist of estrogen receptor alpha (ER) signaling.
2026-01-14 | GSE283161 | GEO
Project description:In individuals where gender identity and sex assigned at birth are markedly and consistently incongruent, as in the case of transgender people, feminisation or masculinisation may be sought through gender affirming hormone therapy (GAHT). In this study we profiled genome-wide DNA methylation in transgender women and transgender men, before and during GAHT (6 months and 12 months into hormone treatment).
2022-02-17 | GSE176394 | GEO
Project description:Clinical treatment protocols for infertility with in vitro fertilization-embryo transfer (IVF-ET) provide a unique opportunity to assess the human vaginal microbiome in defined hormonal milieu. Herein, we have investigated the association of circulating ovarian-derived estradiol (E2) and progesterone (P4) concentrations to the vaginal microbiome. Thirty IVF-ET patients were enrolled in this study, after informed consent. Blood was drawn at four time points during the IVF-ET procedure. In addition, if a pregnancy resulted, blood was drawn at 4-to-6 weeks of gestation. The serum concentrations of E2 and P4 were measured. Vaginal swabs were obtained in different hormonal milieu. Two independent genome-based technologies (and the second assayed in two different ways) were employed to identify the vaginal microbes. The vaginal microbiome underwent a transition with a decrease in E2 (and/or a decrease in P4). Novel bacteria were found in the vagina of 33% of the women undergoing IVF-ET. Our approach has enabled the discovery of novel, previously unidentified bacterial species in the human vagina in different hormonal milieu. While the relationship of hormone concentration and vaginal microbes was found to be complex, the data support a shift in the microbiome of the human vagina during IVF-ET therapy using standard protocols. The data also set the foundation for further studies examining correlations between IVF-ET outcome and the vaginal microbiome within a larger study population.
2011-10-24 | E-MEXP-2958 | biostudies-arrayexpress
Project description:The vaginal microbiome of transgender men receiving gender affirming hormonal therapy in comparison to cisgender woman
| PRJEB71387 | ENA
Project description:Background. Vaginal atrophy (VA) is the thinning of the vaginal epithelial lining, typically the result of lowered estrogen levels during menopause. Some of the consequences of VA include increased susceptibility to bacterial infection, pain during sexual intercourse, and vaginal burning or itching. Although estrogen treatment is highly effective, alternative therapies are also desired for women who are not candidates for hormone replacement therapy (HRT). The ovariectomized (OVX) rat is widely accepted as an appropriate animal model for many estrogen-dependent responses in humans; however, since reproductive biology can vary significantly between mammalian systems, this study examined how well the OVX rat recapitulates human biology at the transcriptional level. This report describes an analysis of expression profiling data, comparing the responses of rat and human vaginae to estrogen treatment. Results. The level of differential expression between pre- vs. post- estrogen treatment was calculated for each of the human and OVX rat datasets. Probe sets corresponding to orthologous rat and human genes were mapped to each other using NCBI Homologene. A positive correlation was observed between the rat and human responses to estrogen. Genes belonging to several biological pathways and GO categories were similarly differentially expressed in rat and human. A large number of the coordinately regulated biological processes are already known to be involved in human VA, such as inflammation, epithelial development, and EGF pathway activation. Conclusions. At the transcriptional level, there is evidence of significant overlap of the effects of estrogen treatment between the OVX rat and human VA samples. Keywords: Disease State Analysis: Animal Model Validation We analyzed vaginal biopsies from 19 woman pre and post 3 month estradiol treatment and compared to OVX rats treated with E2 for 6 hr, 3 days or 5 days (N=5)
2009-05-20 | E-GEOD-11622 | biostudies-arrayexpress
Project description:The mammary gland is a hormone responsive organ and has been extensively studied under the influences of estrogen and progesterone. However, the molecular implications of androgen exposure in the normal breast remain elusive and unexplored, partially due to a lack of relevant tissue to study the functional consequences of androgen action. Transgender men are born female but identify as male, and many choose to undergo gender-affirming androgen therapy, which elicits wide-ranging masculinizing effects that help align their physical characteristics and gender identity. Here we perform single cell resolution profiling of androgen treated breast tissue from transgender men at the transcriptome, chromatin, and spatial level to elucidate the regulatory action of androgen. We show male-biased androgen receptor gene targets are specifically upregulated in androgen receptor expressing cell types, and that other sex-relevant changes are also initiated in cells lacking androgen receptor expression, through paracrine signaling cascades. We observe a functionally and structurally altered epithelium, shifts in immune populations and directed reduction of capillary vasculature. Finally, we discover evidence of the metabolic impact of androgen and demonstrate how the treatment induces fat loss by specifically targeting adipocyte function. This work provides a comprehensive and mechanistic characterization of the mammary tissue responses to androgen activity at single-cell resolution.
2023-03-07 | GSE168837 | GEO
Project description:The mammary gland is a hormone responsive organ and has been extensively studied under the influences of estrogen and progesterone. However, the molecular implications of androgen exposure in the normal breast remain elusive and unexplored, partially due to a lack of relevant tissue to study the functional consequences of androgen action. Transgender men are born female but identify as male, and many choose to undergo gender-affirming androgen therapy, which elicits wide-ranging masculinizing effects that help align their physical characteristics and gender identity. Here we perform single cell resolution profiling of androgen treated breast tissue from transgender men at the transcriptome, chromatin, and spatial level to elucidate the regulatory action of androgen. We show male-biased androgen receptor gene targets are specifically upregulated in androgen receptor expressing cell types, and that other sex-relevant changes are also initiated in cells lacking androgen receptor expression, through paracrine signaling cascades. We observe a functionally and structurally altered epithelium, shifts in immune populations and directed reduction of capillary vasculature. Finally, we discover evidence of the metabolic impact of androgen and demonstrate how the treatment induces fat loss by specifically targeting adipocyte function. This work provides a comprehensive and mechanistic characterization of the mammary tissue responses to androgen activity at single-cell resolution.
2023-03-07 | GSE168836 | GEO
Project description:The dataset consists of longitudinal plasma proteomic data was generated using the Olink proteomics platform in plasma from transgender individuals receiving feminizing gender-affirming hormone therapy (GAHT). There were two treatment arms in the clinical trial that received different anti-androgens to inhibit testosterone. This included a cyproterone acetate ("CPA") group (n=20) and a spironolactone ("SPIRO") group (n=20). Proteomics was measured in plasma at baseline and 6 months following feminizing GAHT. Additionally data in a cross-sectional pregnancy cohort at first and third trimester, as well as a cis female and cis male control were generated.
2025-09-17 | PAD000016 | Pride
Project description:Background: Combination chemotherapy has contributed to increased survival from Hodgkin disease (HD) and testicular cancer (TC). However, questions concerning the quality of spermatozoa after treatment have arisen. While studies have shown evidence of DNA damage and aneuploidy in spermatozoa years following anticancer treatment, the sperm epigenome has received little attention. Our objectives here were to determine the impact of HD and TC, as well as their treatments, on sperm DNA methylation. Semen samples were collected from community controls (CC) and from men undergoing treatment for HD or TC, both before initiation of chemotherapy and at multiple times post-treatment. Sperm DNA methylation was assessed using genome-wide and locus-specific approaches. Results: Imprinted gene methylation was not affected in the sperm of HD or TC men, before or after treatment. Prior to treatment, using Illumina HumanMethylation450 BeadChip (450K) arrays, a subset of 500 probes was able to distinguish sperm samples from TC, HD and CC subjects; differences between groups persisted post-treatment. Comparing altered sperm methylation between HD or TC patients versus CC men, twice as many sites were affected in TC versus HD men; for both groups, the most affected CpGs were hypomethylated. For TC patients, the promoter region of GDF2 contained the largest region of differential methylation. To assess alterations in DNA methylation over time/post-chemotherapy, serial samples from individual patients were compared. With restriction landmark genome scanning and 450K array analyses, some patients who underwent chemotherapy showed increased alterations in DNA methylation, up to two to three years post-treatment, when compared to the CC cohort. Similarly, a higher resolution human sperm-specific assay that includes assessment of environmentally-sensitive regions, or “dynamic sites”, also demonstrated persistently altered sperm DNA methylation in cancer patients post-treatment and suggested preferential susceptibility of “dynamic” CpG sites. Conclusions: Distinct sperm DNA methylation signatures were present pre-treatment in men with HD and TC and may help explain increases in birth defects reported in recent clinical studies. Epigenetic defects in spermatozoa of some cancer survivors were evident even up to two years post-treatment. Abnormalities in the sperm epigenome both pre- and post-chemotherapy may contribute to detrimental effects on future reproductive health.
2023-01-25 | GSE211120 | GEO