ArticleProceedings of the National Academy of Sciences of the United States of America2014
Overexpression of a DENND1A isoform produces a polycystic ovary syndrome theca phenotype.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers, 8 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
117 citing papers in PubMed, 8 syntheses or guidelines pooled it, 255 citations in OpenAlex.
- Metabolic profiling of human follicular fluid to unravel the pathways involved in polycystic ovary syndrome - a systematic review.Reviews in endocrine & metabolic disorders · 2026Pooled it
- Multi-ancestry genome-wide association analyses of polycystic ovary syndrome.Nature genetics · 2025Pooled it
- Body mass index stratified meta-analysis of genome-wide association studies of polycystic ovary syndrome in women of European ancestry.BMC genomics · 2024Pooled it
- Association of FSHR and DENND1A polymorphisms with polycystic ovary syndrome: a meta-analysis.JBRA assisted reproduction · 2023Pooled it
- Insulin-like growth factor binding protein-1 and insulin in polycystic ovary syndrome: a systematic review and meta-analysis.Frontiers in endocrinology · 2023Pooled it
- Replication study and meta-analysis of selected genetic variants and polycystic ovary syndrome susceptibility in Asian population.Journal of assisted reproduction and genetics · 2021Pooled it
- A Comprehensive Overview of Common Polymorphic Variants in Genes Related to Polycystic Ovary Syndrome.Reproductive sciences (Thousand Oaks, Calif.) · 2021Pooled it
- Association of DENND1A Gene Polymorphisms with Polycystic Ovary Syndrome: A Meta-Analysis.Journal of clinical research in pediatric endocrinology · 2016Pooled it
- Kisspeptin treatment induces gonadotropic responses and rescues ovulation in a subset of preclinical models and women with polycystic ovary syndrome.Human reproduction (Oxford, England) · 2019Trial
- Redox biology in PCOS: Biomarkers, mechanistic networks, and targeted interventions (Review).International journal of molecular medicine · 2026Review
- Identification of CA2 as a potential candidate gene involved in the therapeutic effect of Huatan Huoxue decoction on polycystic ovary syndrome: An integrated study of network pharmacology, Mendelian randomization, and experimental validation.Journal of food and drug analysis · 2026Article
- Phenotype-Specific Association ofInternational journal of fertility & sterility · 2026Article
- PCOS and breast cancer risk: hormonal modulation and epidemiological trends.Reproductive health · 2026Review
- Regulatory risk loci link disrupted androgen response to the pathophysiology of polycystic ovary syndrome.Journal of the Endocrine Society · 2026Article
- sc-eQTL unveil immunogenetic architecture of polycystic ovary syndrome.Scientific reports · 2026Article
- Roles of exosomes in microenvironment-related premature ovarian insufficiency: mechanisms and therapeutic intervention.Reproductive biology and endocrinology : RB&E · 2025Review
- On the Intimate Relationship of Adiposity to Polycystic Ovary Syndrome.The Journal of clinical endocrinology and metabolism · 2025Review
- Multimodal Integration of Genomic Data Reveals Regulatory Mechanisms at the Polycystic Ovary Syndrome (PCOS)-Associated 12q13.2 Locus.International journal of molecular sciences · 2025Article
- Review
- The Endocrinological Basis for Polycystic Ovary Syndrome: An Evolutionary Perspective.Endocrinology · 2025Review
57 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Polycystic ovary syndrome (PCOS), characterized by increased ovarian androgen biosynthesis, anovulation, and infertility, affects 5-7% of reproductive-age women. Genome-wide association studies identified PCOS candidate loci that were replicated in subsequent reports, including DENND1A, which encodes a protein associated with clathrin-coated pits where cell-surface receptors reside. However, these studies provided no information about functional roles for DENND1A in the pathogenesis of PCOS. DENND1A protein was located in the cytoplasm as well as nuclei of theca cells, suggesting a possible role in gene regulation. DENND1A immunostaining was more intense in the theca of PCOS ovaries. Using theca cells isolated and propagated from normal cycling and PCOS women, we found that DENND1A variant 2 (DENND1A.V2) protein and mRNA levels are increased in PCOS theca cells. Exosomal DENND1A.V2 RNA was significantly elevated in urine from PCOS women compared with normal cycling women. Forced overexpression of DENND1A.V2 in normal theca cells resulted in a PCOS phenotype of augmented CYP17A1 and CYP11A1 gene transcription, mRNA abundance, and androgen biosynthesis. Knock-down of DENND1A.V2 in PCOS theca cells reduced androgen biosynthesis and CYP17A1 and CYP11A1 gene transcription. An IgG specific to DENND1A.V2 also reduced androgen biosynthesis and CYP17 and CYP11A1 mRNA when added to the medium of cultured PCOS theca cells. We conclude that the PCOS candidate gene, DENND1A, plays a key role in the hyperandrogenemia associated with PCOS. These observations have both diagnostic and therapeutic implications for this common disorder.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.