Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1312987 | ENA |
REPOSITORIES: ENA
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Project description:Esophageal adenocarcinoma (EAC) exhibits marked male predominance with male-to-female ratios reaching 8.5:1, yet the molecular basis underlying this sex disparity remains poorly characterized. We analyzed 92 EAC specimens using mass spectrometry–based proteomics, comprising 47 female and 45 male tumors from treatment-naïve patients. Differential expression, pathway enrichment, immunohistochemical, and survival analyses were used to identify sex-associated proteomic features and prognostic signatures. Proteomic profiling revealed focal yet biologically meaningful sex differences in esophageal adenocarcinoma. After multiple testing correction, three proteins were differentially expressed: the autosomal protein pregnancy zone protein (PZP), enriched in female tumors, and the Y-chromosome–encoded proteins DDX3Y and RPS4Y1, which were overexpressed in male tumors. At nominal significance, proteins upregulated in female tumors showed marked enrichment of immune-related pathways. Proteins correlated with PZP expression formed a network dominated by complement cascade. Clinically, elevated PZP expression was associated with significantly poorer overall survival, most pronounced in male patients and independent of sex-specific survival differences. Proteome-wide survival analyses further demonstrated distinct sex-specific prognostic landscapes. Our study provides the first comprehensive characterization of sex-associated proteomic differences in EAC. Sex shapes immune-related pathways, prognostic proteomic signatures, and survival associations. PZP emerges as a sex-differential, complement-associated protein with adverse prognostic significance, highlighting sex as a biologically and clinically relevant variable in EAC
2026-06-25 | PXD078617 | Pride
Project description:To identify markers associated with inherent cellular sex-identity, we analysed cultured macrophages from male and female chick embryos. We found that male and female macrophages respond differently to stimulation by bacterial lipopolysaccharide and that female macrophages constitutively express higher levels of interferon target genes than male macrophages. To determine whether these differences resulted from the actions of gonadal hormones, we induced gonadal sex-reversal to alter the hormonal environment of the developing chick and analysed different tissues and macrophages from male and female embryos.
2014-07-31 | GSE59919 | GEO
Project description:This SuperSeries is composed of the following subset Series:; GSE9504: Expression data from hybrid female Xenopus sex reversal experiment; GSE9505: Expression data from hybrid male Xenopus sex reversal experiment Experiment Overall Design: Refer to individual Series
2008-06-16 | E-GEOD-9507 | biostudies-arrayexpress
Project description:Expression data from hybrid male Xenopus sex reversal experiment
| PRJNA105173 | ENA
Project description:Purpose: In this study we employed unbiased, genome wide techniques to identify novel enhancers of Sox9 that may cause Disorders of Sex Development (DSDs) when disrupted in the mouse. Methods: We performed ATAC-seq on 60K FACS-purified gonadal cells before and after sex determination to map nucleosome depleted regions (NDRs) indicative of regulatory elements. We then selected 16 putative enhancers present in Sertoli cells. To determine whether these are active enhancers, we performed ChIP-seq for H3K27ac, a histone modification that marks active enhancers. Transient transgenics was performed on select enhancers to determine whether they drive Sertoli-specific expression in vivo. Finally, we selected a single active Sertoli-specific enhancer to delete with CRISPR. Results: We identified a single enhancer upstream of Sox9 that causes complete male-to-female sex reversal in mice when deleted. Conclusions: Our study is the first to identify a single enhacer supstream of Sox9 which drives Sertoli-specific expression in vivo and causes complete male-to-female sex reversal when deleted in the mouse. Furthermore, this enhancer overlaps a region in humans (XY SR) associated to DSDs.
2018-04-12 | GSE99320 | GEO
Project description:Foxl2 is a forkhead transcription factor essential for proper reproductive function in females. It is expressed in the somatic cell population of the gonad (granulosa cells) which forms the follicles of the ovary, the structures responsible for embedding and nurturing the oocytes during their development. FOXL2 directly regulate the aromatase that synthesizes estrogens CYP19A1, thus promoting female differentiation, as well as acting as a repressor of the male factors SOX9 and DMRT1.Expression is also found in the eyelids, pituitary gland and uterus. In the goat, frog and many fish species FOXL2 is a sex-determining gene which, when deleted, leads to female-to-male sex reversal.
2022-07-11 | PXD024439 | Pride
Project description:Developmental gene expression is defined through cross-talk between the function of transcription factors and epigenetic status including histone modification. Although several known transcription factors play crucial roles in mammalian sex determination, how chromatin regulation contributes to this process is unknown. We observed male-to-female sex reversal in mice lacking the H3K9 demethylase Jmjd1a, and found that Jmjd1a directly regulates expression of the mammalian Y chromosome sex-determining gene Sry, by regulating H3K9me2 marks. These studies reveal a pivotal role for epigenetic regulation in mammalian sex determination, and provide new impetus for identifying additional causes of disorders of sex determination by environmental factors.
2013-08-03 | GSE49513 | GEO
Project description:Sexual reproduction is nearly universal among multicellular animals, but sex can be determined by cues including sex chromosomes, temperature, social status, and photoperiod. DMRT transcription factors are key regulators of sex in animals that use diverse sex-determining strategies. These proteins are related to the sexual regulators Doublesex (Dsx) and Male abnormal-3 (MAB-3) of insects and nematodes, respectively. DMRT proteins share the DM DNA binding domain, comprised of a unique intertwined double zinc-binding module flanked by a C-terminal recognition helix that binds to a pseudopalindromic target DNA. Despite the central role of DMRT proteins in metazoan sexual development, how they recognize target DNA sequences is poorly understood. Here we find that DMRT proteins employ multiple DNA binding modes due to surprising versatility in how specific base contacts are made. Human DMRT1 can bind as a dimer, trimer or tetramer, in each case using paired antiparallel recognition helices that together insert into a widened DNA major groove to make base-specific contacts. Insertion of two helices in a single major groove is, to our knowledge, a DNA binding interaction unique to DMRT proteins. High resolution in vivo DNA binding analysis (ChIP-Exo) indicates that multiple DNA binding modes also are used in the mouse testis. Finally, we show that mutations affecting amino acid residues crucial for DNA recognition are associated with sex reversal in flies and also, for the first time, with male-to-female sex reversal in humans. Our results illuminate an ancient molecular interaction that underlies much of metazoan sexual development.
2015-05-18 | GSE64892 | GEO