Cited by 555Ovarian function and disordersSexual Differentiation and DisordersReproductive Biology and Fertility

The DOI matches its Crossref record; 226 of the 231 references it cites were found in a registry or an index.

Androgen excess fetal programming of female reproduction: a developmental aetiology for polycystic ovary syndrome

Abbott, D.H., Barnett, D.K., Bruns, C.M., Dumesic, D.A.·2005·Human Reproduction Update

Open this paper in CoChat — free account

Abstract

The aetiology of polycystic ovary syndrome (PCOS) remains unknown. This familial syndrome is prevalent among reproductive-aged women and its inheritance indicates a dominant regulatory gene with incomplete penetrance. However, promising candidate genes have proven unreliable as markers for the PCOS phenotype. This lack of genetic linkage may represent both extreme heterogeneity of PCOS and difficulty in establishing a universally accepted PCOS diagnosis. Nevertheless, hyperandrogenism is one of the most consistently expressed PCOS traits. Animal models that mimic fetal androgen excess may thus provide unique insight into the origins of the PCOS syndrome. Many female mammals exposed to androgen excess in utero or during early post-natal life typically show masculinized and defeminized behaviour, ovulatory dysfunction and virilized genitalia, although behavioural and ovulatory dysfunction can coexist without virilized genitalia based upon the timing of androgen excess. One animal model shows particular relevance to PCOS: the prenatally androgenized female rhesus monkey. Females exposed to androgen excess early in gestation exhibit hyperandrogenism, oligomenorrhoea and enlarged, polyfollicular ovaries, in addition to LH hypersecretion, impaired embryo development, insulin resistance accompanying abdominal obesity, impaired insulin response to glucose and hyperlipidaemia. Female monkeys exposed to androgen excess late in gestation mimic these programmed changes, except for LH and insulin secretion defects. In utero androgen excess may thus variably perturb multiple organ system programming and thereby provide a single, fetal origin for a heterogeneous adult syndrome.

Integrity signals

Registry

Crossref · 10.1093/humupd/dmi013

Cites

226 of 226 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome
(2004) · Fertility and Sterility · doi:10.1016/j.fertnstert.2003.10.004 · Cited by 9,050
Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS)
The Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group (2004) · Human Reproduction · doi:10.1093/humrep/deh098 · Cited by 6,138
A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif
Sinclair, A. H., Berta, P., Palmer, M. S., Hawkins, J. R., Griffiths, B. L., Smith, M. J., Foster, J. W., Frischauf, A., Lovell-Badge, R. H., & Goodfellow, P. N. (1990) · Nature · doi:10.1038/346240a0 · Cited by 3,234
Insulin Resistance and the Polycystic Ovary Syndrome: Mechanism and Implications for Pathogenesis
Dunaif, A. E. (1997) · Endocrine Reviews · doi:10.1210/edrv.18.6.0318 · Cited by 2,776
The Prevalence and Features of the Polycystic Ovary Syndrome in an Unselected Population
Azziz, R., Woods, K. S., Reyna, R., Key, T. J., Knochenhauer, E. S., & Yıldız, B. O. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-032046 · Cited by 2,715
Estrogen Resistance Caused by a Mutation in the Estrogen-Receptor Gene in a Man
Smith, E. P., Boyd, J., Frank, G. R., Takahashi, H., Cohen, R. M., Specker, B., Williams, T. C., Lubahn, D. B., & Korach, K. S. (1994) · New England Journal of Medicine · doi:10.1056/nejm199410203311604 · Cited by 2,471
Polycystic Ovary Syndrome
Franks, S. (1995) · New England Journal of Medicine · doi:10.1056/nejm199509283331307 · Cited by 2,463
Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: A prospective, controlled study in 254 affected women
Legro, R. S. (1999) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.84.1.165 · Cited by 1,743
Androgen Receptor Defects: Historical, Clinical, and Molecular Perspectives*
Quigley, C. A., Bellis, A. D., Marschke, K. B., Awady, M. K. E., Wilson, E. M., & French, F. S. (1995) · Endocrine Reviews · doi:10.1210/edrv-16-3-271 · Cited by 1,459
Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens
Morishima, A., Grumbach, M. M., Simpson, E. R., Fisher, C., & Qin, K. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.80.12.8530621 · Cited by 1,416

Flagged first, then by citations

Show all 231 references

5 of the 231 references couldn’t be matched to a known paper.

Research works printed but not linked: 8

Dewailly D, Cortet-Rudelli C and Deroubaix-Allard D (1997) Definition, clinical manifestations, and prevalence of PCOS. In Azziz R, Nestler JE, and Dewailly D (eds) Androgen Excess Disorders in Women. Lippincott-Raven Publishers, Philadelphia, PA, pp 259–268.
Fischer DA (2003) Endocrinology of fetal development. In Larsen PR, Kronenberg HM, Melmed S, and Polonsky KS (eds) Williams Textbook of Endocrinology. 10th edn. WB Saunders, Philadelphia, PA, pp 811–841.
Goy RW and Kemnitz JW (1983) Early, persistent, and delayed effects of virilizing substances delivered transplacentally to female rhesus fetuses. In Zbinden G, Cuomo V, Racagni G, and Weiss B (eds) Application of Behavioral Pharmacology in Toxicology. Raven Press, New York, pp 303–314.
Goy RW, Uno H and Sholl SA (1988) Psychological and anatomical consequences of prenatal exposure to androgens in female rhesus. In Mori T and Nagasawa H (eds) Toxicity of Hormones in Perinatal Life. CRC Press, Inc., Boca Raton, Florida, pp 127–142.
Hoar RM and Monie IW (1981) Comparative development of specific organ systems. In Kimmel CA and Buelke-Sam J (eds) Developmental Toxicology. Raven Press, New York, pp 13–33.
Knobil E and Hotchkiss J (1994) The menstrual cycle and its neuroendocrine control. In Knobil E, Neill J, Ewing LL, Greenwald GS, Markert CL, and Pfaff DW (eds) The Physiology of Reproduction, Vol 2. Raven Press, New York, pp 1971–1994.
Short RV (1974) Sexual differentiation of the brain of the sheep. In Forest MG and Bertrand J (eds) Sexual endocrinology of the perinatal period, Colloque International INSERM, Lyon. INSERM, Paris, France pp. 121–142.
Sperling MA (1994) Carbohydrate metabolism: insulin and glucagons. In Tulchinsky D and Little AB (eds) Maternal–Fetal Endocrinology. 2nd edn. WB Saunders, Philadelphia, PA, pp 380–400.

Sorted by citations

Items 201–300 of 554

Prenatal androgen excess negatively impacts body fat distribution in a nonhuman primate model of polycystic ovary syndrome
Bruns, C. M., Baum, S. T., Colman, R. J., Dumesic, D. A., Eisner, J., Jensen, M. D., Whigham, L. D., & Abbott, D. H. (2007) · International Journal of Obesity · doi:10.1038/sj.ijo.0803638 · Cited by 44
Ovarian and extra-ovarian mediators in the development of polycystic ovary syndrome
Puttabyatappa, M., & Padmanabhan, V. (2018) · Journal of Molecular Endocrinology · doi:10.1530/jme-18-0079 · Cited by 43
Ovarian SAHA syndrome is associated with a more insulin-resistant profile and represents an independent risk factor for glucose abnormalities in women with polycystic ovary syndrome: A prospective controlled study
Dalamaga, Μ., Papadavid, E., Basios, G., Vaggopoulos, V., Rigopoulos, D., Kassanos, D., & Trakakis, E. (2013) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2013.09.014 · Cited by 42
Attention deficit-hyperactivity disorder symptoms in women with polycystic ovary syndrome
Hergüner, S., HARMANCI, H., & Toy, H. (2015) · The International Journal of Psychiatry in Medicine · doi:10.1177/0091217415610311 · Cited by 42
“These results suggest that androgen exposure may have an effect on hyperactivity and impulsivity in women with PCOS.”
Influential
Polycystic Ovary Syndrome and Hyperandrogenic States
Chang, R. J., & Dumesic, D. A. (2019) · Elsevier eBooks · doi:10.1016/b978-0-323-47912-7.00021-4 · Cited by 41
Naturally Occurring and Experimentally Induced Rhesus Macaque Models for Polycystic Ovary Syndrome: Translational Gateways to Clinical Application
Abbott, D. H., Rogers, J., Dumesic, D. A., & Levine, J. E. (2019) · Medical Sciences · doi:10.3390/medsci7120107 · Cited by 42
Abnormal infant islet morphology precedes insulin resistance in PCOS-like monkeys
Nicol, L. E., O’Brien, T. D., Dumesic, D. A., Grogan, T., Tarantal, A. F., & Abbott, D. H. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106527 · Cited by 41
“Studies with nonhuman primates (NHP), sheep, rats and mice have suggested an epigenetic mechanism for PCOS based upon in utero exposure of the developing female fetus to androgen excess and associated metabolic consequences [3,4,5,6]; a hypothesis supported by evidence of an altered epigenome in visceral adipose tissu…”
BackgroundMethodInfluential
Pathophysiologic Mechanisms of Insulin Secretion and Signaling-Related Genes in Etiology of Polycystic Ovary Syndrome
Shaaban, Z., Khoradmehr, A., Amiri‐Yekta, A., Nowzari, F., Shirazi, M. R. J., & Tamadon, A. (2021) · Genetics Research · doi:10.1155/2021/7781823 · Cited by 46
Effect of quercetin on steroidogenesis and folliculogenesis in ovary of mice with experimentally-induced polycystic ovarian syndrome
Shah, M. Z. U. H., Shrivastva, V. K., Mir, M. A., Sheikh, W. M., Ganie, M. A., Rather, G. A., Shafi, M., Bashir, S. M., Ansari, M. A., Aljafary, M. A., et al. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1153289 · Cited by 42
“As was already mentioned, a significant factor in PCOS is hyperandrogenism (6).”
Developmental programming of polycystic ovary syndrome (PCOS): prenatal androgens establish pancreatic islet α/β cell ratio and subsequent insulin secretion
Ramaswamy, S., Grace, C., Mattei, A. A., Siemienowicz, K. J., Brownlee, W., MacCallum, J., McNeilly, A. S., Duncan, W. C., & Rae, M. T. (2016) · Scientific Reports · doi:10.1038/srep27408 · Cited by 42
Transcript abundance of stromal and thecal cell related genes during bovine ovarian development
Hatzirodos, N., Hummitzsch, K., Irving‐Rodgers, H. F., Breen, J., Perry, V. E. A., Anderson, R. A., & Rodgers, R. J. (2019) · PLoS ONE · doi:10.1371/journal.pone.0213575 · Cited by 41
Genome-wide methylation profiling in granulosa lutein cells of women with polycystic ovary syndrome (PCOS)
Makrinou, E., Drong, A., Christopoulos, G., Lerner, A., Chapa-Chorda, I., Karaderi, T., Lavery, S. A., Hardy, K., Lindgren, C. M., & Franks, S. (2019) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2019.110611 · Cited by 45
Circulating maternal testosterone concentrations at 18 weeks of gestation predict circulating levels of antimüllerian hormone in adolescence: a prospective cohort study
Hart, R. J., Sloboda, D. M., Doherty, D. A., Norman, R. J., Atkinson, H. C., Newnham, J. P., Dickinson, J. E., & Hickey, M. (2010) · Fertility and Sterility · doi:10.1016/j.fertnstert.2009.12.060 · Cited by 41
Unilateral sectioning of the superior ovarian nerve of rats with polycystic ovarian syndrome restores ovulation in the innervated ovary
Morales‐Ledesma, L., Linares, R., Rosas, G., Morán, C., Chavira, R., Cárdenas, M., & Domı́nguez, R. (2010) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-8-99 · Cited by 40
“Treating new-born rats with testosterone propionate (TP) or progesterone (P4) resulted in endocrine and histological disorders, similar to those found in women with PCOS syndrome [ 9 ].”
Background
A guide to understanding polycystic ovary syndrome (PCOS)
Duncan, W. C. (2014) · Journal of Family Planning and Reproductive Health Care · doi:10.1136/jfprhc-2012-100505 · Cited by 40
Digit ratios do not serve as anatomical evidence of prenatal androgen exposure in clinical phenotypes of polycystic ovary syndrome
Lujan, M. E., Bloski, T. G., Chizen, D. R., Lehotay, D. C., & Pierson, R. A. (2010) · Human Reproduction · doi:10.1093/humrep/dep363 · Cited by 49
“showed that pregnant rhesus monkeys receiving daily injections of testosterone propionate at various stages of gestation had androgenized female offspring that demonstrated variable levels of reproductive and metabolic disturbance, consistent with features of PCOS in humans [Reviewed in (Abbott et al., 2005)].”
Background
Epigenética del síndrome de ovario poliquístico
Francisca Concha, C., Teresa Sir, P., Recabarren, S. E., & Francisco Pérez, B. (2017) · Revista médica de Chile · doi:10.4067/s0034-98872017000700907 · Cited by 38
Serum Anti-Müllerian hormone (AMH) in mothers with polycystic ovary syndrome (PCOS) and their term fetuses
Detti, L., Christiansen, M. E., Francillon, L., Ikuwezunma, G., Diamond, M. P., Mari, G., & Tobiasz, A. (2018) · Systems Biology in Reproductive Medicine · doi:10.1080/19396368.2018.1537385 · Cited by 38
Cardiometabolic abnormalities in the polycystic ovary syndrome: Pharmacotherapeutic insights
Westerveld, H. E., Hoogendoorn, M., de Jong, A. W. F., Goverde, A. J., Fauser, B. C. J. M., & Dallinga‐Thie, G. M. (2008) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2008.04.009 · Cited by 38
Long-term treatment with dehydroepiandrosterone may lead to follicular atresia through interaction with anti-Mullerian hormone
Ikeda, K., Baba, T., 森下, 美., Honnma, H., Endo, T., Kiya, T., & Saito, T. (2014) · Journal of Ovarian Research · doi:10.1186/1757-2215-7-46 · Cited by 37
“the timing and duration of the androgen administration, as well as the amount of hormone administered [4-6].”
Background
CHAPTER 10 – Follicular Development: Mouse, Sheep, and Human Models
Rajkovic, A., Pangas, S. A., & Matzuk, M. M. (2006) · Cited by 39
Developmental Programming: Contribution of Epigenetic Enzymes to Antral Follicular Defects in the Sheep Model of PCOS
Guo, X., Puttabyatappa, M., Thompson, R. C., & Padmanabhan, V. (2019) · Endocrinology · doi:10.1210/en.2019-00389 · Cited by 38
A rational approach to the diagnosis of polycystic ovarian syndrome during adolescence
Merino, P. M., Codner, E., & Cassorla, F. (2011) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302011000800013 · Cited by 35
“Prenatal exposure to androgens, demonstrated in animal studies (56,57), and in daughters of PCOS mothers (58-60), suggest that these conditions are associated with an adverse metabolic profile during childhood and puberty, similar to that seen in PCOS, and with higher AMH levels.”
Background
Androgen-induced epigenetic modulations in the ovary
Salinas, I., Sinha, N., & Sen, A. (2021) · Journal of Endocrinology · doi:10.1530/joe-20-0578 · Cited by 36
Gallic acid reverses ovarian disturbances in mice with letrozole-induced PCOS via modulating Adipo R1 expression
Shah, M. Z. U. H., Soni, M., Shrivastava, V. K., Mir, M. A., & Bashir, S. M. (2022) · Toxicology Reports · doi:10.1016/j.toxrep.2022.10.009 · Cited by 37
“As was previously stated, hyperandrogenism is a major contributor to PCOS [24].”
Background
Translational Insight Into Polycystic Ovary Syndrome (PCOS) From Female Monkeys with PCOS-like Traits
Abbott, D., Levine, J. E., & Dumesic, D. A. (2016) · Current Pharmaceutical Design · doi:10.2174/1381612822666160715133437 · Cited by 36
“T-exposed fetal females thus resemble fetal males in precocious development of negative feedback regulation of GnRH/LH [28], likely mediated through de-sensitized estradiol and/or progesterone mediated mechanisms [13, 18, 29, 30].”
Background
Polycystic ovary syndrome and periodontal disease: Underlying links- A review
Tanguturi, S. C., & Nagarakanti, S. (2018) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/ijem.ijem_577_17 · Cited by 37
“Abbott et al.[28] suggested that the clinical features of PCOS may develop as a consequence of genetically determined hypersecretion of androgens by the ovary.”
Background
Do women with polycystic ovary syndrome (PCOS) report differences in sex-typed behavior as children and adolescents?: Results of a pilot study
Manlove, H. A., Guillermo, C. J., & Gray, P. B. (2008) · Annals of Human Biology · doi:10.1080/03014460802337067 · Cited by 35
“When these perinatally androgenized daughters reached adulthood, they exhibited phenotypes resembling those of the PCOS consensus and typical symptoms including menstrual irregularities, polycystic ovaries and insulin resistance (Abbott et al. 1998, 2005).”
Role of genomic DNA methylation in PCOS pathogenesis: a systematic review and meta-analysis involving case-controlled clinical studies
Rawat, K., Sandhu, A., Gautam, V., Saha, P. K., & Saha, L. (2022) · Molecular Human Reproduction · doi:10.1093/molehr/gaac024 · Cited by 34
Effect of metformin and flutamide on insulin, lipogenic and androgen-estrogen signaling, and cardiometabolic risk in a PCOS-prone metabolic syndrome rodent model
Kupreeva, M., Diané, A., Lehner, R. S., Watts, R., Ghosh, M., Proctor, S. D., & Vine, D. F. (2018) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00018.2018 · Cited by 34
Polycystic ovarian syndrome – prognosis and treatment outcomes
Hart, R. J. (2007) · Current Opinion in Obstetrics & Gynecology · doi:10.1097/gco.0b013e3282f10e22 · Cited by 34
Polycystic Ovary Syndrome with Endometrial Hyperplasia in a Cynomolgus Monkey (Macaca fascicularis)
Arifin, E., Shively, C. A., Register, T. C., & Cline, J. M. (2008) · Veterinary Pathology · doi:10.1354/vp.45-4-512 · Cited by 34
Androgen receptor's destiny in mammalian oocytes: a new hypothesis
Li, M., Schatten, H., & Sun, Q. (2009) · Molecular Human Reproduction · doi:10.1093/molehr/gap006 · Cited by 34
“which resemble polycystic ovaries found in women with PCOS (Abbott et al., 2005; Drummond, 2006).”
Background
TNF-α haplotype association with polycystic ovary syndrome – a South Indian study
Deepika, M., Reddy, K. R., Yashwanth, A. L., Rani, V. U., Latha, K. P., & Jahan, P. (2013) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-013-0080-4 · Cited by 33
“Furthermore, studies have also demonstrated that high lipid and low-fiber diet is related to an increased androgen circulating levels leading to hyperandrogenism; a factor involved in the causation of PCOS [39].”
Background
Experimental models of polycystic ovary syndrome: An update
Divyashree, S., Janhavi, P., Veeranna, R. P., & Peddha, M. S. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.116911 · Cited by 33
Recent advances in mammalian reproductive biology
Wen, L., Liu, Q., Xu, J.-J., Liu, X., Shi, C.-Y., Yang, Z., Zhang, Y., Xu, H., Liu, J., Yang, H., et al. (2019) · Science China Life Sciences · doi:10.1007/s11427-019-1572-7 · Cited by 33
Mild androgen phenotypes
Carmina, E. (2006) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2006.02.001 · Cited by 33
Ovarian and adipose tissue dysfunction in polycystic ovary syndrome: report of the 4th special scientific meeting of the Androgen Excess and PCOS Society
Yıldız, B. O., & Azziz, R. (2009) · Fertility and Sterility · doi:10.1016/j.fertnstert.2009.03.058 · Cited by 33
Early prenatal androgenization results in diminished ovarian reserve in adult female rhesus monkeys
Dumesic, D. A., Patankar, M. S., Barnett, D. K., Lesnick, T. G., Hutcherson, B. A., & Abbott, D. H. (2009) · Human Reproduction · doi:10.1093/humrep/dep324 · Cited by 33
The epigenomics of polycystic ovarian syndrome: from pathogenesis to clinical manifestations
Li, S., Zhu, D., Duan, H., & Tan, Q. (2016) · Gynecological Endocrinology · doi:10.1080/09513590.2016.1203409 · Cited by 32
“The genetic (nature) and nongenetic (nurture) involvements in the expression of PCOS have been demonstrated by twin and family studies with estimated heritability as high as over 60% [2] and by animal studies showing PCOS-like phenotypes including ovarian dysfunction, induced by prenatal exposure to excessive androgen…”
Background
Developmental Programming of Ovarian Functions and Dysfunctions
Puttabyatappa, M., & Padmanabhan, V. (2018) · Vitamins and hormones · doi:10.1016/bs.vh.2018.01.017 · Cited by 32
Revisiting the serum level of anti-Müllerian hormone in patients with functional hypothalamic anovulation
Makolle, S., Catteau-Jonard, S., Robin, G., & Dewailly, D. (2021) · Human Reproduction · doi:10.1093/humrep/deab024 · Cited by 32
The role of androgen receptor activity mediated by the CAG repeat polymorphism in the pathogenesis of PCOS.
Băculescu, N. (2013) · Europe PMC (PubMed Central) · Cited by 32
Polycystic ovary syndrome (PCOS) trilogy: a translational and clinical review
Mason, H. D., Colao, A., Blume‐Peytavi, U., Rice, S., Qureshi, A., Pellatt, L. J., Orio, F., & Atkin, S. L. (2008) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2008.03329.x · Cited by 33
Maternal androgen levels during pregnancy are associated with early-life growth in Geoffroy’s marmosets, Callithrix geoffroyi
Smith, A. S., Birnie, A. K., & French, J. A. (2009) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2009.10.008 · Cited by 31
“PCOS women give birth to babies who are more likely to be small-for-gestational-age than babies from normal mothers (Homburg, 2006) and have increased abdominal fat in later life (Abbott et al., 2005).”
Background
Prenatal programming of neuroendocrine reproductive function
Evans, N. P., Bellingham, M., & Robinson, J. E. (2016) · Theriogenology · doi:10.1016/j.theriogenology.2016.04.047 · Cited by 34
Telomeric repeat‐containing RNA ( TERRA ) related to polycystic ovary syndrome ( PCOS )
Wang, C., Shen, F., Zhu, Y., Fang, Y., & Lü, S. (2016) · Clinical Endocrinology · doi:10.1111/cen.13283 · Cited by 31
Disturbance in Maternal Environment Leads to Abnormal Synaptic Instability during Neuronal Circuitry Development
Hatanaka, Y., Kabuta, T., & Wada, K. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00035 · Cited by 31
“Polycystic ovary syndrome (PCOS), characterized by ovarian dysfunction, and polycystic ovarian morphology in women of childbearing age, leads to excessive levels of male hormones, a condition called hyperandrogenism (Franks, 1995; Abbott et al., 2005; Azziz et al., 2005; Goodarzi et al., 2011), and children from PCOS…”
Background
The obesogen tributyltin induces features of polycystic ovary syndrome (PCOS): a review
Merlo, E., Silva, I. V., Cardoso, R. C., & Graceli, J. B. (2018) · Journal of Toxicology and Environmental Health Part B · doi:10.1080/10937404.2018.1496214 · Cited by 32
“Hyperandrogenism is the most consistent endocrine perturbation detected in PCOS (Abbott et al. 2005).”
Background
Hyperandrogenemia alters mitochondrial structure and function in the oocytes of obese mouse with polycystic ovary syndrome
Chappell, N. R., Zhou, B., Hosseinzadeh, P., Schutt, A. K., Gibbons, W. E., & Blesson, C. S. (2020) · F&S Science · doi:10.1016/j.xfss.2020.12.001 · Cited by 32
Insulin Resistance in PCOS
Diamanti‐Kandarakis, E., & Christakou, C. D. (2009) · Springer eBooks · doi:10.1007/978-0-387-09718-3_4 · Cited by 32
Hormones and Human Partnering
van Anders, S. M., & Gray, P. B. (2007) · Annual Review of Sex Research · doi:10.1080/10532528.2007.10559847 · Cited by 32
Prenatal Testosterone Exposure Worsen the Reproductive Performance of Male Rat at Adulthood
Tehrani, F. R., Noroozzadeh, M., Zahediasl, S., Ghasemi, A., Piryaei, A., & Azizi, F. (2013) · PLoS ONE · doi:10.1371/journal.pone.0071705 · Cited by 31
“induced reproductive disorders in female rats [3,15].”
NMR Metabolomics Show Evidence for Mitochondrial Oxidative Stress in a Mouse Model of Polycystic Ovary Syndrome
Alpergin, E. S. S., Bolandnazar, Z., Tonelli, M., Bütz, D. E., Haviland, J. A., Porter, W. P., & Assadi‐Porter, F. M. (2015) · Journal of Proteome Research · doi:10.1021/acs.jproteome.5b00307 · Cited by 31
Explore the potential molecular mechanism of polycystic ovarian syndrome by protein–protein interaction network analysis
Chen, Q., Zheng, B., Du, S., & Lin, Y. (2021) · Taiwanese Journal of Obstetrics and Gynecology · doi:10.1016/j.tjog.2021.07.005 · Cited by 30
Sexual function and hormonal profiles in women with and without polycystic ovary syndrome: a population-based study
Noroozzadeh, M., Tehrani, F. R., Mobarakabadi, S. S., Farahmand, M., & Dovom, M. R. (2016) · International Journal of Impotence Research · doi:10.1038/ijir.2016.35 · Cited by 30
Chronic androgen excess in female mice does not impact luteinizing hormone pulse frequency or putative GABAergic inputs to GnRH neurons
Coyle, C. S., Prescott, M., Handelsman, D. J., Walters, K. A., & Campbell, R. E. (2022) · Journal of Neuroendocrinology · doi:10.1111/jne.13110 · Cited by 28
Hormone Therapy in Adults: Suggested Revisions to the Sixth Version of the Standards of Care
Feldman, J., & Safer, J. D. (2009) · International Journal of Transgenderism · doi:10.1080/15532730903383757 · Cited by 31
The impact of prenatal exposure to a single dose of testosterone on insulin resistance, glucose tolerance and lipid profile of female rat’s offspring in adulthood
Noroozzadeh, M., Tehrani, F. R., Sedaghat, K., Godini, A., & Azizi, F. (2014) · Journal of Endocrinological Investigation · doi:10.1007/s40618-014-0198-y · Cited by 29
“Similar to our finding in this study, insulin resistance has previously been reported in monkey, sheep and rat models of PCOS [10, 16, 20].”
BackgroundResultInfluential
Cryptotanshinone reverses reproductive and metabolic disturbances in prenatally androgenized rats via regulation of ovarian signaling mechanisms and androgen synthesis
Yang, X., Zhang, Y., Wu, X., Bae, C. S., Hou, L., Kuang, H., Wang, Y., & Stener‐Victorin, E. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00334.2010 · Cited by 29
Fetal androgen exposure is a determinant of adult male metabolic health
Siemienowicz, K. J., Filis, P., Shaw, S., Douglas, A., Thomas, J. L., Mulroy, S., Howie, F. A., Fowler, P., Duncan, W. C., & Rae, M. T. (2019) · Scientific Reports · doi:10.1038/s41598-019-56790-4 · Cited by 28
Transient anomalies in genital appearance in some extremely preterm female infants may be the result of foetal programming causing a surge in LH and the over activation of the pituitary–gonadal axis
Greaves, R. F., Hunt, R. W., & Zacharin, M. (2008) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2008.03298.x · Cited by 28
Androgens Regulate Ovarian Gene Expression Through Modulation of Ezh2 Expression and Activity
Ma, X., Hayes, E. T., Biswas, A., Seger, C., Prizant, H., Hammes, S. R., & Sen, A. (2017) · Endocrinology · doi:10.1210/en.2017-00145 · Cited by 28
Differential Effects of Prenatal Testosterone Timing and Duration on Phenotypic and Behavioral Masculinization and Defeminization of Female Sheep1
Roberts, E. K., Padmanabhan, V., & Lee, T. M. (2008) · Biology of Reproduction · doi:10.1095/biolreprod.107.067074 · Cited by 28
“The disruption of reproductive physiology by excess prenatal testosterone during a critical period of fetal or neonatal life has been demonstrated in several species, including guinea pig [4], rat [5], sheep [6–9], rhesus macaque [10, 11], and human [12].”
Background
Developmental androgen excess disrupts reproduction and energy homeostasis in adult male mice
Nohara, K., Liu, S., Meyers, M. S., Waget, A., Ferron, M., Karsenty, G., Burcelin, R., & Mauvais-Jarvis, F. (2013) · Journal of Endocrinology · doi:10.1530/joe-13-0230 · Cited by 28
“…most common endocrine disorder in females of reproductive age and is believed to have a developmental origin in which maternal and fetal androgen excess during pregnancy programs both the reproductive and metabolic abnormalities of the offspring (Abbott et al. 2005, Xita & Tsatsoulis 2006, 2010).”
Obesity and Familial Predisposition Are Significant Determining Factors of an Adverse Metabolic Profile in Young Patients with Congenital Adrenal Hyperplasia
Moreira, R. P. P., Villares, S. M., Madureira, G., Mendonca, B. B., & Bachega, T. A. S. S. (2013) · Hormone Research in Paediatrics · doi:10.1159/000353762 · Cited by 29
Prenatal exposures and birth indices, and subsequent risk of polycystic ovary syndrome: a national registry‐based cohort study
Valgeirsdottir, H., Vanky, E., Poromaa, I. S., Roos, N., Løvvik, T. S., Stephansson, O., & Wikström, A. (2018) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/1471-0528.15236 · Cited by 26
Fetal programming of polycystic ovary syndrome: Effects of androgen exposure on prenatal ovarian development
Barsky, M., Merkison, J. M., Hosseinzadeh, P., Yang, L., Bruno-Gaston, J., Dunn, J., Gibbons, W. E., & Blesson, C. S. (2021) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2021.105830 · Cited by 26
“PCOS is known to have strong familial clustering, demonstrated in identical twin studies, exhibiting a heritable element, with hyperandrogenism the most heritable trait [2, 3].”
Background
Maternal urinary bisphenols and phthalates in relation to estimated fetal weight across mid to late pregnancy
Cowell, W., Jacobson, M. H., Long, S. E., Wang, Y., Kahn, L. G., Ghassabian, A., Naidu, M., Torshizi, G. D., Afanasyeva, Y., Liu, M., et al. (2023) · Environment International · doi:10.1016/j.envint.2023.107922 · Cited by 26
The ratio of anterior anogenital distance to posterior anogenital distance
ŞİMŞİR, Ç., Pekcan, M. K., Aksoy, R. T., Ecemiş, T., Çoşkun, B., Kilic, S. H., & Tokmak, A. (2019) · Journal of the Chinese Medical Association · doi:10.1097/jcma.0000000000000150 · Cited by 26
“PCOS was diagnosed based on Rotterdam criteria15 in the presence of at least two of the following: (1) oligomenorrhea and/or anovulation, (2) biochemical and/or clinical hyperandrogenism, (3) ultrasound detection of polycystic ovaries (PCO) (multiple cysts >12 in number of 2-9 mm size) along with exclusion of other et…”
Method
Industrial endocrine disruptors and polycystic ovary syndrome
Palioura, E., & Diamanti‐Kandarakis, E. (2013) · Journal of Endocrinological Investigation · doi:10.1007/bf03346762 · Cited by 27
Electroacupuncture Mimics Exercise-Induced Changes in Skeletal Muscle Gene Expression in Women With Polycystic Ovary Syndrome
Benrick, A., Pillon, N. J., Nilsson, E., Lindgren, E., Krook, A., Ling, C., & Stener‐Victorin, E. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa165 · Cited by 26
“For example, androgen exposure during fetal life leads to epigenetic reprograming, which in adulthood might lead to the development of PCOS (8, 9) A hallmark of PCOS is hyperinsulinemia, and these women typically exhibit decreased insulin sensitivity and decreased whole-body glucose uptake, which…”
Background
Assessment of antioxidant status of women with polycystic ovarian syndrome
Oyebanji, O., & Asaolu, M. F. (2020) · Asian Pacific Journal of Reproduction · doi:10.4103/2305-0500.275523 · Cited by 24
“Also, disruption of ovulatory function (anovulation) in PCOS may result from both altered steroid negative feedback regulation of luteinizing hormone and the compensatory hyperinsulinemia caused by insulin resistance[4].”
Background
Basal and dynamic relationships between serum anti-Müllerian hormone and gonadotropins in patients with functional hypothalamic amenorrhea, with or without polycystic ovarian morphology
Hager, M., Ott, J., Marschalek, J., Marschalek, M., Kinsky, C., Marculescu, R., & Dewailly, D. (2022) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-022-00961-y · Cited by 24
“In detail, these modulations could affect granulosa cells by means of their richness and/or affinity of FSH and/ or androgen receptors [35, 36].”
Background
Somatic cell fate maintenance in mouse fetal testes via autocrine/paracrine action of AMH and activin B
Rodriguez, K. F., Brown, P. R., Amato, C. M., Nicol, B., Liu, C., Xu, X. M., & Yao, H. H. (2022) · Nature Communications · doi:10.1038/s41467-022-31486-y · Cited by 24
Molecular Mechanisms in the Etiology of Polycystic Ovary Syndrome (PCOS): A Multifaceted Hypothesis Towards the Disease with Potential Therapeutics
Nisa, K. U., Tarfeen, N., Mir, S. A., Waza, A. A., Ahmad, M. B., & Ganai, B. A. (2023) · Indian Journal of Clinical Biochemistry · doi:10.1007/s12291-023-01130-7 · Cited by 28
“Also, increased LH surge results in the follicular arrest at preantral and antral stages leading to hyperplasia of theca cells and the development of multiple follicles along the periphery of ovary [50].”
Genetic approaches to polycystic ovarian syndrome
Menke, M., & Strauss, J. F. (2007) · Current Opinion in Obstetrics & Gynecology · doi:10.1097/gco.0b013e328220e877 · Cited by 24
Digit ratios by computer-assisted analysis confirm lack of anatomical evidence of prenatal androgen exposure in clinical phenotypes of polycystic ovary syndrome
Lujan, M. E., Podolski, A. J., Chizen, D. R., Lehotay, D. C., & Pierson, R. A. (2010) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-8-156 · Cited by 24
Pregnancy and neonatal complications in women with polycystic ovary syndrome in relation to second-trimester anti-Müllerian hormone levels
Valdimarsdottir, R., Valgeirsdottir, H., Wikström, A., Kallak, T. K., Elenis, E., Axelssön, O., Ubhayasekhera, K., Bergquist, J., Piltonen, T., Pigny, P., et al. (2019) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2019.02.004 · Cited by 25
Obesity in Adolescent Girls: Is Excess Androgen the Real Bad Actor?
Marshall, J. C. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2665 · Cited by 24
“In both sheep and monkeys, exposure to high levels of androgen in utero led to abnormalities of LH secretion during subsequent puberty, with elevated plasma LH, persistently rapid GnRH frequency, and impaired ovarian steroid feedback (21, 22).”
Background
Continuum of Symptoms in Polycystic Ovary Syndrome (PCOS): Links with Sexual Behavior and Unrestricted Sociosexuality
Tzalazidis, R., & Oinonen, K. A. (2020) · The Journal of Sex Research · doi:10.1080/00224499.2020.1726273 · Cited by 23
Embryos from polycystic ovary syndrome patients with hyperandrogenemia reach morula stage faster than controls
Chappell, N. R., Barsky, M., Shah, J. S., Peavey, M. C., Yang, L., Sangi‐Haghpeykar, H., Gibbons, W. E., & Blesson, C. S. (2020) · F&S Reports · doi:10.1016/j.xfre.2020.05.006 · Cited by 23
Congenital adrenal hyperplasia
Demirci, C., & Witchel, S. F. (2008) · Dermatologic Therapy · doi:10.1111/j.1529-8019.2008.00216.x · Cited by 22
“Data supporting this mechanism are derived from studies involving nonhuman primates in which prenatal androgen treatment was associated with postnatal hyperandrogenism, oligo-ovulation, and polycystic ovaries (33).”
Background
Polycystic ovary syndrome: Recent research and therapeutic advancements
Dilliyappan, S., Kumar, A. S., Venkatesalu, S., Palaniyandi, T., Baskar, G., Sivaji, A., Rab, S. O., Saeed, M., & Shivaranjani, K. S. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.123221 · Cited by 26
Chlorogenic Acid Restores Ovarian Functions in Mice with Letrozole-Induced Polycystic Ovarian Syndrome Via Modulation of Adiponectin Receptor
Shah, M. Z. U. H., Shrivastava, V. K., Sofi, S., Jamous, Y. F., Khan, M. F., Alkholifi, F. K., Ahmad, W., & Mir, M. A. (2023) · Biomedicines · doi:10.3390/biomedicines11030900 · Cited by 23
Prenatal testosterone exposure as a model for the study of endocrine-disrupting chemicals on the gerbil prostate
Biancardi, M. F., Perez, A. P., Góes, R. M., Santos, F. C., Vilamaior, P. S. L., & Taboga, S. R. (2012) · Experimental Biology and Medicine · doi:10.1258/ebm.2012.012051 · Cited by 22
The Epigenetic Basis of Adaptation and Responses to Environmental Change: Perspective on Human Reproduction
Fernández, A. F., Toraño, E. G., Urdinguio, R. G., Lana, A. G., Arnott, I., & Fraga, M. F. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-0820-2_6 · Cited by 22
Ovarian Androgens Maintain High GnRH Neuron Firing Rate in Adult Prenatally-Androgenized Female Mice
Dulka, E. A., Burger, L. L., & Moenter, S. M. (2019) · Endocrinology · doi:10.1210/endocr/bqz038 · Cited by 22
Abnormal instability, excess density, and aberrant morphology of dendritic spines in prenatally testosterone-exposed mice
Hatanaka, Y., Wada, K., & Kabuta, T. (2015) · Neurochemistry International · doi:10.1016/j.neuint.2015.04.008 · Cited by 23
Androgen levels and metabolic parameters are associated with a genetic variant of F13A1 in women with polycystic ovary syndrome
Schweighofer, N., Lerchbaum, E., Trummer, O., Schwetz, V., Pilz, S., Pieber, T. R., & Obermayer-Pietsch, B. M. (2012) · Gene · doi:10.1016/j.gene.2012.04.050 · Cited by 22
Follicular Development
Pangas, S. A., & Rajkovic, A. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-397175-3.00021-1 · Cited by 22
Sex differences and effects of prenatal exposure to excess testosterone on ventral tegmental area dopamine neurons in adult sheep
Brown, E. C. Z., Steadman, C. J., Lee, T. M., Padmanabhan, V., Lehman, M. N., & Coolen, L. M. (2015) · European Journal of Neuroscience · doi:10.1111/ejn.12871 · Cited by 21
“…and behavior have been documented in several species including rat (Wolf et al., 2002; Wu et al., 2010), rhesus macaque (Goy et al., 1988; Abbott et al., 2005), human (Merke & Bornstein, 2005) and sheep (Wood & Foster, 1998; Robinson et al., 2002; Padmanabhan et al., 2006; Bormann et…”
Background
Pathology of hyperandrogenemia in the oocyte of polycystic ovary syndrome
Chappell, N. R., Gibbons, W. E., & Blesson, C. S. (2022) · Steroids · doi:10.1016/j.steroids.2022.108989 · Cited by 23
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
Accelerated Episodic Luteinizing Hormone Release Accompanies Blunted Progesterone Regulation in PCOS-like Female Rhesus Monkeys (Macaca Mulatta) Exposed to Testosterone during Early-to-Mid Gestation
Abbott, D. H., Vepraskas, S., Horton, T. H., Terasawa, E., & Levine, J. E. (2018) · Neuroendocrinology · doi:10.1159/000490570 · Cited by 21
Foetal Sonographic Anogenital Distance Is Longer in Polycystic Ovary Syndrome Mothers
Perlman, S., Toledano, Y., Kivilevitch, Z., Halevy, N., Rubin, E., & Gilboa, Y. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9092863 · Cited by 20
“Although the aetiology of PCOS is unclear, prenatal exposure to androgen hormones is considered an important factor in the development of this metabolic reproductive endocrine disorder [34,35].”
Background
Comparative transcriptomic analysis reveals reproductive impairments caused by PCBs and OH-PCBs through the dysregulation of ER and AR signaling
Tam, N. Y.-K., Lai, K. P., & Kong, R. Y. C. (2021) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2021.149913 · Cited by 20
Supraphysiological leptin levels shift the profile of steroidogenesis in porcine ovarian follicles toward progesterone and testosterone secretion through increased expressions of CYP11A1 and 17β-HSD: a tissue culture approach
Gregoraszczuk, E. Ł., & Rak, A. (2013) · Reproduction · doi:10.1530/rep-12-0269 · Cited by 20
“…both clinical and animal studies suggests that PCOS is a developmental syndrome that manifests in adolescence and adulthood, in which exposure to excess androgens during the fetal or prepubertal phases of growth essentially ‘reprograms’ multiple tissues (Abbott et al. 2005, Xita & Tsatsoulis 2009).”
Background
Early onset adiposity: a pathway to polycystic ovary syndrome in adolescents?
Diamanti‐Kandarakis, E., Christakou, C. D., Kandaraki, E., & Alexandraki, K. (2007) · PubMed · Cited by 20
Elevated expression of steroidogenesis pathway genes; CYP17, GATA6 and StAR in prenatally androgenized rats
Jahromi, M. S., Tehrani, F. R., Noroozzadeh, M., Zarkesh, M., Ghasemi, A., & Zadeh–Vakili, A. (2016) · Gene · doi:10.1016/j.gene.2016.07.067 · Cited by 20

Authors: Abbott, D. H., Barnett, D. K., Bruns, C. M., & Dumesic, D. A.
Corresponding author: Abbott, D.H.
ORCID: Abbott, D.H.
Dumesic, D.A.
Venue: Human Reproduction Update
Publisher: Oxford University Press (OUP)
Published: 2005-07-01
Volume: 11
Issue: 4
Pages: 357-374
ISSN: 1355-4786 (ISSN-L)
1460-2369
DOI: 10.1093/humupd/dmi013
OpenAlex: W2123009569
Cited by: 555
References: 231
Citations by year: 2026: 9 · 2025: 17 · 2024: 24 · 2023: 27 · 2022: 27 · 2021: 21 · 2020: 27 · 2019: 37 · 2018: 23 · 2017: 30 · 2016: 34 · 2015: 28 · 2014: 32 · 2013: 31 · 2012: 23
FWCI: 4.24
Type: journal article
Language: en
Open access: closed
Locations: Human Reproduction Update (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5u01hd044650-05)
National Institute on Aging (T32AG000268)
National Center for Research Resources (R01RR013635, R21RR014093, P51RR000167)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD044405, U01-HD044650)
Topics: Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
Keywords: polycystic ovary syndrome, hyperandrogenism, fetal programming, developmental origins of health and disease, rhesus monkeys, prenatal androgen exposure, ovulatory dysfunction, insulin resistance, hyperlipidemia
MeSH terms: Androgens, Animals, Female, Genitalia, Female, Humans, Polycystic Ovary Syndrome, Hyperandrogenism

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Androgen excess fetal programming of female reproduction: a developmental aetiology for polycystic ovary syndrome

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks