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Overexpression of a DENND1A isoform produces a polycystic ovary syndrome theca phenotype
Open accessAbstract
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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“Overexpression of the alternative spliced variant, DENND1A.V2, of this gene recapitulated a PCOS phenotype in cultured theca cells obtained from normal women, indicating a role for this variant in the excessive theca cell androgen production [27].”
From Polycystic Ovary Syndrome: Pathophysiology, Presentation, and Treatment With Emphasis on Adolescent Girls (2019) · cites this paper as [27]
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DENND1A gene variants in Bahraini Arab women with polycystic ovary syndrome
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“Overexpression of variant 2 DENND1A, alternative splicing of DENND1A, in PCOS theca cells was observed, which can contribute to androgen overproduction in these cells (86).”
BackgroundGao, J., Xue, J., Li, Z., Zhou, L., & Chen, C. (2016) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-016-4159-x · Cited by 24
“V2 gene was knocked down among PCOS patients, the theca cells would come to be normal phenotype [30].”
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“The ZNF217 pAdenoG Null were used to infect normal theca cells as we previously described [16].”
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Tian-Min, Y., Suxia, L., Ding, S., Cao, D., Long-Dan, L., & Yeung, W. S. B. (2022) · Disease Markers · doi:10.1155/2022/4000424 · Cited by 27
“The expression of DENND1A variant 2 mRNA was significantly increased in urine exosomes from women with PCOS compared with normal cycling women [13].”
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“It has been suggested that one susceptibility gene which may be involved in the pathophysiology of PCOS is a polymorphism of DENND1A [16] which may induce hyperandrogenism and at the same time promote an alteration of early ovarian follicle development [17].”
RetractedLei, L., Ding, L., Su, J., Liu, M., Shi, Q., Zhou, J., Sun, H., & Yan, G. (2017) · PLoS ONE · doi:10.1371/journal.pone.0187427 · Cited by 23
PCOS: update and diagnostic approach
Goldrat, O., & Delbaere, A. (2018) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2018.09.001 · Cited by 24
miRNA expression in PCOS: unveiling a paradigm shift toward biomarker discovery
Rashid, G., Khan, N. A., Elsori, D. H., Youness, R. A., Hassan, H., Siwan, D., Seth, N., Kamal, M. A., Rizvi, S., Babker, A. M. A., et al. (2024) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-024-07379-4 · Cited by 24
“V2 has been associated with differential expression of miRNAs, which needs to be further elucidated in PCOS theca cells vs. normal cells [38].”
Dallel, M., Sarray, S., Douma, Z., Hachani, F., Al-Ansari, A. K., Letaifa, D. B., Mahjoub, T., & Almawi, W. Y. (2018) · Gene · doi:10.1016/j.gene.2018.01.028 · Cited by 23
chi-miR-324-3p Regulates Goat Granulosa Cell Proliferation by Targeting DENND1A
Liu, Y., Chen, Y., Zhou, Z., He, X., Tao, L., Jiang, Y., Rong, L., Hong, Q., & Chu, M. (2021) · Frontiers in Veterinary Science · doi:10.3389/fvets.2021.732440 · Cited by 20
“Furthermore, high methylation existed in the DENND1A intron in aging oocytes (16, 27).”
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Cellular and Animal Studies: Insights into Pathophysiology and Therapy of PCOS
Indran, I. R., Lee, B. H., & Yong, E. (2016) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2016.03.006 · Cited by 21
Ye, B., Duan, B., Deng, W., Wang, Y., Chen, Y., Cui, J., Sun, S., Zhang, Y., Du, J., Gu, L., et al. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01343 · Cited by 20
“Studies have shown that DENND1A is highly expressed in patients with polycystic ovary syndrome (PCOS) and plays a catalytic role in its development (Eriksen et al., 2013; McAllister et al., 2014).”
BackgroundDennd1a, a susceptibility gene for polycystic ovary syndrome, is essential for mouse embryogenesis
Shi, J., Gao, Q., Cao, Y., & Fu, J. (2019) · Developmental Dynamics · doi:10.1002/dvdy.28 · Cited by 20
“Moreover, knock-down of a DENND1A isoform in isolated PCOS theca cell cultures reduced the androgen biosynthesis, indicating that DENND1A plays a key role in the hyperandrogenemia associated with PCOS.14 However, to date, little is known about how the DENND1A gene function in developmental and reproductive processes.”
BackgroundInfluentialPuberty in the Female and Its Disorders
Rosenfield, R. L., Cooke, D. W., & Radovick, S. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-62520-3.00016-6 · Cited by 23
Understanding polycystic ovary syndrome in light of associated key genes
Bhimwal, T., Puneet, & Priyadarshani, A. (2023) · Egyptian Journal of Medical Human Genetics · doi:10.1186/s43042-023-00418-w · Cited by 21
“Over-expression of DENND1A (DENN/ MADD domain containing 1A) in theca cells of PCOS females has a significant role in elevated androgen and progestin synthesis [112].”
BackgroundGenetic basis of eugonadal and hypogonadal female reproductive disorders
Trofimova, T., Lizneva, D., Сутурина, Л. В., Walker, W., Chen, Y.-H., Azziz, R., & Layman, L. C. (2017) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2017.05.003 · Cited by 19
AMH inhibits androgen production in human theca cells
Chen, M., Guo, X., Zhong, Y., Liu, Y., Bing, C., Wu, R., Huang, C. Z., & Zhou, C. (2022) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2022.106216 · Cited by 18
An Evolutionary Model for the Ancient Origins of Polycystic Ovary Syndrome
Dumesic, D. A., Abbott, D. H., & Chazenbalk, G. D. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12196120 · Cited by 17
“A post-transcription form of DENND1A , namely DENND1A.v2, is over-expressed in some PCOS women [47,48], with DENND1A.v2 over-expression in human theca cells increasing androgen biosynthesis/release, potentially through PCOS-candidate gene ZNF217 diminishing the theca cell expression of microRNA…”
BackgroundHyperandrogenism, Hirsutism, and Polycystic Ovary Syndrome
Rosenfield, R. L., Barnes, R. B., & Ehrmann, D. A. (2015) · Elsevier eBooks · doi:10.1016/b978-0-323-18907-1.00133-5 · Cited by 17
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Carmina, E. (2015) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2015.07.006 · Cited by 16
Bishop, C. V., Xu, F., Xu, J., Ting, A. Y., Galbreath, E., McGee, W. K., Zelinski, M. B., Hennebold, J. D., Cameron, J. L., & Stouffer, R. L. (2015) · Fertility and Sterility · doi:10.1016/j.fertnstert.2015.11.045 · Cited by 16
“The function of DENND1A is in membrane associated endocytosis and receptor trafficking; there is some evidence that expression of a DENND1A variant increases androgen production in a human theca cell model (51).”
BackgroundAssociation of DENND1A Gene Polymorphisms with Polycystic Ovary Syndrome: A Meta-Analysis
Bao, S., Cai, J.-H., Yang, S.-Y., Ren, Y., Tian, F., Jin, T., & Li, Z.-R. (2016) · Journal of Clinical Research in Pediatric Endocrinology · doi:10.4274/jcrpe.2259 · Cited by 16
“The DENN domain containing 1a (DENND1A) gene, a member of a family of 18 human genes termed “connecdenns”, has gained recognition as a strong PCOS susceptibility gene in several studies (4,5).”
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Zheng, J., Deng, T., Jiang, E., Li, J., Wijayanti, D., Wang, Y., Ding, X., & Lan, X. (2021) · Gene · doi:10.1016/j.gene.2021.145867 · Cited by 15
The Search for the Causes of Common Hyperandrogenism, 1965 to Circa 2015
Rosenfield, R. L. (2024) · Endocrine Reviews · doi:10.1210/endrev/bnae007 · Cited by 16
Polycystic ovary syndrome in adolescent girls
Baldauff, N. H., & Witchel, S. F. (2016) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000309 · Cited by 14
Intertwined reproductive endocrinology: Puberty and polycystic ovary syndrome
Witchel, S. F., & Plant, T. M. (2020) · Current Opinion in Endocrine and Metabolic Research · doi:10.1016/j.coemr.2020.07.004 · Cited by 15
“Conversely, knockdown of this variant in PCOS theca cells decreased androgen production and CYP17A1 expression [63].”
BackgroundPolycystic Ovary Syndrome and the Neuroendocrine Consequences of Androgen Excess
Silva, M. S. B., & Campbell, R. E. (2022) · Comprehensive physiology · doi:10.1002/cphy.c210025 · Cited by 22
Diagnosis and treatment of polycystic ovary syndrome (PCOS): An interview with Richard Legro
Legro, R. S. (2015) · BMC Medicine · doi:10.1186/s12916-015-0299-2 · Cited by 15
“See references [1-10].”
Female Genomics: Infertility and Overall Health
Joshi, N., & Chan, J. L. (2017) · Seminars in Reproductive Medicine · doi:10.1055/s-0037-1603095 · Cited by 13
Li, J., Cui, L., Jiang, X., Zhao, H., Zhao, S., Shi, Y., Wei, D., Li, Y., Ma, J., & Chen, Z. (2020) · Human Reproduction · doi:10.1093/humrep/deaa125 · Cited by 13
Liu, X., Xu, M., Qian, M., & Yang, L. (2021) · Endocrine Connections · doi:10.1530/ec-21-0327 · Cited by 13
“V2, a splice variant of PCOS candidate locus, enhanced CYP17A1 and CYP11A1 gene expression in theca cells and induced the cells to synthesize more androgen (45).”
Zhu, Y.-N., Zhang, Y., Liu, Q., Shen, S., Zou, X., Cao, Y., Wang, W., Yi, L., Gao, Q., Yang, W.-D., et al. (2020) · BMC Medical Genetics · doi:10.1186/s12881-019-0945-1 · Cited by 13
“V2 in theca cells can promote CYP17A1 and CYP11A1 gene transcription and androgen synthesis, leading to hyperandrogenemia of PCOS [13].”
BackgroundInfluentialPharmacologic Treatment of Polycystic Ovary Syndrome: Alternate and Future Paths
Legro, R. S., & Martel‐Duguech, L. (2017) · Seminars in Reproductive Medicine · doi:10.1055/s-0037-1603729 · Cited by 11
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Veiga‐Lopez, A., Moeller, J., Abbott, D. H., & Padmanabhan, V. (2016) · Journal of Ovarian Research · doi:10.1186/s13048-016-0250-y · Cited by 12
Kadıoğlu, E., Altun, B., İpek, Ç., Döğer, E., Bıdecı, A., Attaran, H., & Çok, İ. (2018) · Molecular Biology Reports · doi:10.1007/s11033-018-4380-8 · Cited by 12
Ramanathan, B., Murugan, J., & Velayutham, K. (2021) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/ijem.ijem_340_21 · Cited by 12
“McAllister et al.[15] reported that the intronic variants in DENND1A lack apparent functions that would favor splicing of V2 over V1 and these DENND1A V2 are overexpressed in the PCOS theca cells.”
BackgroundSankaranarayanan, L., Brewer, K., Morrow, S., Johnson, G. D., Barrera, A., Venukuttan, R., Sisk, R. K., Dunaif, A. E., & Reddy, T. E. (2025) · Nature Communications · doi:10.1038/s41467-025-62884-7 · Cited by 12
“DENND1A expressionhasbeenimplicatedinandrogen biosynthesis 22 – 24 , in ovarian theca cell and H295R cell model 27 .”
InfluentialPCOS: An heterogeneous condition with multiple faces for multiple doctors
Bouchard, P., & Fauser, B. C. J. M. (2014) · European Journal of Endocrinology · doi:10.1530/eje-14-0429 · Cited by 11
Cao, P., Li, H., Wang, P., Zhang, X., Guo, Y., Zhao, K., Guo, J., Li, X., & Nashun, B. (2024) · American Journal Of Pathology · doi:10.1016/j.ajpath.2024.02.003 · Cited by 10
Anti-Müllerian Hormone: A Molecular Key to Unlocking Polycystic Ovary Syndrome?
Abbott, D. H., Hutcherson, B. A., & Dumesic, D. A. (2024) · Seminars in Reproductive Medicine · doi:10.1055/s-0044-1787525 · Cited by 10
“In vitro studies inducing DENND1A.v2 overexpression in non-PCOS human ovarian theca cells, nevertheless, increase theca cell production and release of testosterone, 85 and knockdown of DENND1A.v2 inhibitors increases CYP17A.”
BackgroundExtracellular vesicles in reproductive medicines
Mokhtari, K., Sheykhhasan, M., Shahnazari, M., Ahmadieh-Yazdi, A., Shokrollah, N., Samadi, P., & Yang, P. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-23891-8.00006-8 · Cited by 9
On the Intimate Relationship of Adiposity to Polycystic Ovary Syndrome
Rosenfield, R. L., & Dumesic, D. A. (2025) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaf527 · Cited by 11
Chen, Z., Pan, X., Kong, Y., Jiang, Y., Zhong, Y., Zhang, H., Zhang, Z., Yuan, X., & Li, J. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00135 · Cited by 9
“Importantly, we identified 17 circRNAs that were differentially expressed in the gilts, for which we speculated that some parental genes of differentially regulated circRNAs could influence the fertility and production traits of female mammals, such as ESR1 (Handa and Weiser, 2014), DENND1A (McAllister et al., 2014),…”
BackgroundDharani, V., Nishu, S., & Lakshmanan, H. (2025) · Reproductive Biology · doi:10.1016/j.repbio.2025.101017 · Cited by 11
Genetic and Environmental Factors in the Etiology of Polycystic Ovary Syndrome
Barber, T. M., & Franks, S. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-813209-8.00027-3 · Cited by 10
Epigenetic Marks in Polycystic Ovary Syndrome
Motta, A. B. (2019) · Current Medicinal Chemistry · doi:10.2174/0929867326666191003154548 · Cited by 8
Androgen production and action in the ovary
Franks, S. (2021) · Current Opinion in Endocrine and Metabolic Research · doi:10.1016/j.coemr.2021.02.002 · Cited by 10
Shah, R. D. (2019) · Children · doi:10.3390/children6080089 · Cited by 9
Regenerative Medicine Perspectives in Polycystic Ovary Syndrome
Arjmand, B., Alaei, S., Heravani, N. F., Alavi-Moghadam, S., Payab, M., Ebrahimpour, M., Aghayan, H. R., Goodarzi, P., & Larijani, B. A. (2021) · Advances in experimental medicine and biology · doi:10.1007/5584_2021_623 · Cited by 8
Candelaria, N. R., & Richards, J. S. (2024) · Biology of Reproduction · doi:10.1093/biolre/ioae010 · Cited by 7
“Polycystic ovary syndrome (PCOS) is a common anovulatory endocrine disorder in women [1–6].”
BackgroundPolycystic Ovary Syndrome Endocrine and Cardio-Metabolic Abnormalities: how to Manage?
Georgescu, C. E. (2015) · Acta Endocrinologica (Bucharest) · doi:10.4183/aeb.2015.77 · Cited by 7
Developmental origins of polycystic ovary syndrome: Everything starts in utero
Abbott, D. H., Greinwald, E. P., & Levine, J. E. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-823045-9.00009-2 · Cited by 9
Transgenic Mouse Models to Study the Development and Maintenance of the Adrenal Cortex
Nader, N. A., Zamberlam, G., & Boyer, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232214388 · Cited by 7
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“Recently, the functional roles for DENND1A in the pathogenesis of PCOS were proved to be involved in androgen production [15].”
BackgroundTinano, F. R., Machado, I. F. R., Latronico, A. C., & Gomes, L. G. (2025) · Journal of Neuroscience · doi:10.1523/jneurosci.1681-24.2024 · Cited by 8
Joseph, S., Ubba, V., Wang, Z., Feng, M., Dsilva, M. K., Suero, S., Waheed, D., Snyder, N. W., Yang, X., Wang, H., et al. (2025) · Endocrinology · doi:10.1210/endocr/bqaf071 · Cited by 6
PCOS research from the past to the future
Yıldız, B. O. (2025) · Nature Reviews Endocrinology · doi:10.1038/s41574-025-01174-0 · Cited by 6
Unraveling PCOS therapies: Pharmacotherapeutic strategies and emerging therapeutic targets
Shirasath, K. R., Ahmed, N. Z., Kumar, P., Alam, S., Karwasra, R., Goyal, S. N., & Agrawal, Y. O. (2025) · Pathology - Research and Practice · doi:10.1016/j.prp.2025.156245 · Cited by 7
Understanding reproductive endocrine disorders
Kaiser, U. B. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.179 · Cited by 6
DENND1A desensitizes granulosa cells to FSH by arresting intracellular FSHR transportation
Dou, Y., Zhao, R., Wu, H., Yu, Z., Yin, C., Yang, J., Yang, C., Luan, X., Cheng, Y., Huang, T., et al. (2024) · Science China Life Sciences · doi:10.1007/s11427-023-2438-4 · Cited by 6
“V2 , the truncated transcript, and PCOS through androgen synthesis in ovarian theca cells (McAllister et al., 2014; Tee et al., 2016).”
InfluentialWaldman, I. N., & Legro, R. S. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-813209-8.00026-1 · Cited by 6
Association of FSHR and DENND1A polymorphisms with polycystic ovary syndrome: a meta-analysis
Larsen, C. B., Kúdela, E., & Biringer, K. (2022) · JBRA · doi:10.5935/1518-0557.20220043 · Cited by 6
“Contrarily, when they tried to reduce these levels, the androgen synthesis was decreased, and the authors concluded that DENND1A plays a role in hyperandrogenemia in women with PCOS (McAllister et al., 2014).”
BackgroundBucheeri, S., Alcibahy, Y., Bucheeri, Y., Bucheeri, S., Alhermi, A., & Butler, A. E. (2025) · Cells · doi:10.3390/cells14221769 · Cited by 8
“V2 functionally linked to excess androgen production in PCOS theca cells [57,58].”
The Role of Gene Alterations in the Pathogenesis of Polycystic Ovary Syndrome
Carmina, E. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14103347 · Cited by 5
“The increased expression of the DENND1A gene seems particularly important in determining hyperandrogenism in PCOS [12–17 , 19–”
Polycystic Ovary Syndrome: From Phenotype to Genotype
Laven, J. S. E., & Louwers, Y. V. (2022) · Cambridge University Press eBooks · doi:10.1017/9781108989831.002 · Cited by 5
Shao, S., Xu, Q., Zi, Y., Zheng, X., Chen, S., Qin, C., Zhao, H., & Li, X. (2024) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2024.12.043 · Cited by 4
Navigating the Future of PCOS Treatment: The Precision Medicine Paradigm
Sunil, A. T., Jo, C., Sanigha, P. S., Kolasseri, A. E., Tamizhselvi, R., & Jayanthi, S. (2024) · Current pharmacogenomics and personalized medicine (Online)/Current pharmacogenomics and personalized medicine · doi:10.2174/0118756921331801240820115132 · Cited by 5
Chaker, W. M.-M., Adi, R. M., Madkour, M. I., Farhat, N. M., Abdelrahim, D. N., Saber-Ayad, M. M., Muhammad, J. S., Mohammed, G., Mousa, N. A., Saadi, A., et al. (2025) · Journal of Nutrition and Metabolism · doi:10.1155/jnme/8817919 · Cited by 4
The Endocrinological Basis for Polycystic Ovary Syndrome: An Evolutionary Perspective
Dumesic, D. A., Crespi, B. J., Padmanabhan, V., & Abbott, D. H. (2025) · Endocrinology · doi:10.1210/endocr/bqaf160 · Cited by 4
Epigenetic and transgenerational transmission of polycystic ovary syndrome
Stener‐Victorin, E. (2020) · Current Opinion in Endocrine and Metabolic Research · doi:10.1016/j.coemr.2020.03.005 · Cited by 4
Ibrahim, Z. M., Kishk, E. A., Fahmy, S. M., & Taha, O. T. (2020) · Obstetrics and Gynecology Reports · doi:10.15761/ogr.1000141 · Cited by 4
“Intrinsic abnormalities in ovarian steroidogenesis may underlie this ovarian dysfunction in some patients [4].”
BackgroundRoles of Extracellular Vesicles in Human Reproduction
Zhou, W., Zhang, T., Lian, Y., & Zhang, W. (2021) · Physiology · doi:10.5772/intechopen.101046 · Cited by 4
Selection signatures in goats reveal a novel deletion mutant underlying cashmere yield and diameter
Han, H., Yang, M.-M., Dan, J., Chao, S.-Y., Zhang, X.-J., Wei, Q., Chen, T., Wang, Q.-J., Yang, C.-Y., Wulan, B., et al. (2022) · GigaScience · doi:10.1093/gigascience/giac107 · Cited by 4
“…DENND1A and CRB2 are associated with polycystic ovary syndrome (PCOS) and maintenance of apicobasal polarity in the retinal pigment epithelium, respectively, but without evidence in hair development [26, 27]; another gene, LHX2 near DENND1A , plays an important role in hair follicle development.”
Adipositas – polyzystisches Ovarialsyndrom – Krebs
Weiss, J., & Küpker, W. (2017) · Gynäkologische Endokrinologie · doi:10.1007/s10304-017-0133-3 · Cited by 5
Le syndrome des ovaires polykystiques : quelles nouveautés en 2019 ?
Gourbesville, C., Kerlan, V., & Reznik, Y. (2019) · Annales d Endocrinologie · doi:10.1016/s0003-4266(19)30114-3 · Cited by 5
Exploration of Alternative Splicing (AS) Events in MDV-Infected Chicken Spleens
Wang, L., Zheng, G., Yuan, Y., Wang, Z., Liu, C., Zhang, H., & Lian, L. (2021) · Genes · doi:10.3390/genes12121857 · Cited by 4
“Additionally, DENND1A was also related to gastric cancer [84], endometrial carcinoma [85].”
BackgroundInterface between reproductive and metabolic dysfunction in polycystic ovary syndrome
Rasouli, M. A., Katz, J., & Dumesic, D. A. (2025) · Current Opinion in Obstetrics & Gynecology · doi:10.1097/gco.0000000000001037 · Cited by 5
A SYSTEMIC REVIEW ON DIFFERENTIAL REGULATION OF GENES IN POLYCYSTIC OVARIAN SYNDROME DISEASE
Mary, M. J., Deecaraman, M., Vijayalakshmi, M., & Umashankar, V. (2015) · International Journal of Pharma and Bio Sciences · Cited by 3
The Genetics of Polycystic Ovary Syndrome: From Genome-Wide Association to Molecular Mechanisms
Strauss, J. F., Modi, B. P., & McAllister, J. M. (2018) · Reproductive medicine for clinicians · doi:10.1007/978-3-319-78009-2_3 · Cited by 3
Ovarian Dysfunction in Polycystic Ovary Syndrome (PCOS)
Mason, H. D., Dilaver, N., & Rice, S. (2022) · Springer eBooks · doi:10.1007/978-3-030-92589-5_6 · Cited by 3
Morales-Esponda, M., Aguilar, R. D. L. S., Villanueva-Rodríguez, R., Oliva, L. D. S., Aguilar-Salinas, C. A., Chirinos, M., & Larrea, F. (2025) · Revista de investigaci�n Cl�nica · doi:10.1016/j.ric.2025.100008 · Cited by 2
Yang, Y., Rui, B., & Kim, J. H. (2025) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-025-01514-9 · Cited by 2
sc-eQTL unveil immunogenetic architecture of polycystic ovary syndrome
Xu, X., Bao, Y., Zhang, Q., Wang, L., & Wang, H. M. (2026) · Scientific Reports · doi:10.1038/s41598-025-34726-5 · Cited by 2
“2A )( Supplementary Table S2) , including DENND1A and THADA with known metabolic functions 30–32 .”
The pathogenic role of androgen excess in PCOS
Pignatelli, D., Pereira, S. S., & Kandaraki, E. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-823045-9.00017-1 · Cited by 4
DENND1A and THADA Gene Polymorphism Among Iraqi Women With Polycystic Ovary Syndrome
Alizzi, F. J., Kokaz, H. T., & Al-Mayah, Q. S. (2019) · International Journal of Women s Health and Reproduction Sciences · doi:10.15296/ijwhr.2020.43 · Cited by 2
“that overexpress the mutant DENND1A (8).”
BackgroundHu, H., Yang, M., Dan, J., Zhang, X., Wei, Q., Chen, T., Wang, Q.-J., Yang, C., Wulan, B., Zhang, T., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.11.06.467539 · Cited by 2
“…with polycystic ovary syndrome (PCOS) and maintenance of apicobasal polarity in retinal pigment epithelium, respectively, but without evidence in hair development (McAllister et al. 2014; Paniagua et al. 2021); while another gene LHX2 near DENND1A, plays important role in hair follicle development.”
BackgroundRichards, J. S. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.64624-x · Cited by 2
Gene regulatory activity associated with PCOS revealed DENND1A -dependent testosterone productionPreprint
Sankaranarayanan, L., Brewer, K., Johnson, G. D., Barrera, A., Venukuttan, R., Sisk, R. K., Dunaif, A. E., & Reddy, T. E. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.23.595551 · Cited by 2
Wu, F., Feng, J., Wang, H., Wang, S., Cui, X., Liu, Y., Yan, L., Ye, K., Thorne, R. F., Zhang, X. D., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1541209 · Cited by 1
Kosta, S., & Singh, M. C. (2025) · Obstetrics and gynecology. · doi:10.5772/intechopen.1012249 · Cited by 2
Familial Aggregation and Contribution of Various Genes in PCOS
Mathur, S. K., & Purwar, N. (2025) · BENTHAM SCIENCE PUBLISHERS eBooks · doi:10.2174/9798898810931125010017 · Cited by 1
The role of genetic and epigenetic factors in developing polycystic ovary syndrome
Koval, Y. E., Дмитриевна, К. Т., Игнатко, И. В., Bakhtiyarov, K. R., Gilmutdinova, I., & Владимировна, В. Е. (2026) · Obstetrics Gynecology and Reproduction · doi:10.17749/2313-7347/ob.gyn.rep.2026.766 · Cited by 1
Thirumurugan, A., Ravi, S., & Annamalai, A. (2026) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2026.107088 · Cited by 1
Integrative approaches for the management of PCOS: A review
Joshi, A., Muthal, A., Namdeo, A. G., & Shinde, V. M. (2023) · International Journal of Herbal Medicine · doi:10.22271/flora.2023.v11.i2a.856 · Cited by 1
Haidar, Z., Banu, H., Morshed, M. S., Akhteruzzaman, S., Hasanat, M. A., & Sajib, A. A. (2024) · Gene Reports · doi:10.1016/j.genrep.2024.101888 · Cited by 1
Metadata
- Authors
- McAllister, J. M., Modi, B., Miller, B. A., Biegler, J., Bruggeman, R., Legro, R. S., & Strauss, J. F.
- Affiliations
- Pennsylvania State University (US)
- Virginia Commonwealth University (US)
- Departments of aPathology and
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-03-31
- Volume
- 111
- Issue
- 15
- Pages
- E1519-27
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3992676
- OpenAlex
- W1984174412
- Cited by
- 250
- References
- 54
- Citations by year
- 2026: 10 · 2025: 23 · 2024: 32 · 2023: 13 · 2022: 19 · 2021: 25 · 2020: 24 · 2019: 19 · 2018: 16 · 2017: 15 · 2016: 25 · 2015: 20 · 2014: 9
- FWCI
- 27.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Virginia Commonwealth University
- National Institutes of Health (UL1TR000127, U54HD344449)
- U.S. Public Health Service (UL1T000058, UL1T0000127)
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD33852, U54HD344449, R01HD033852, R01HD058300)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Keywords
- polycystic ovary syndrome, DENND1A, theca cells, androgen production, CYP17A1, CYP11A1, hyperandrogenemia, exosomal RNA, urinary biomarkers, clathrin-coated pits, gene overexpression
- MeSH terms
- Analysis of Variance, Androgens, Cholesterol Side-Chain Cleavage Enzyme, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunoglobulin G, Immunohistochemistry, Polycystic Ovary Syndrome, Steroid 17-alpha-Hydroxylase, Theca Cells, Hyperandrogenism, Protein Isoforms, Guanine Nucleotide Exchange Factors, Death Domain Receptor Signaling Adaptor Proteins, Genome-Wide Association Study, Real-Time Polymerase Chain Reaction
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