“High Profile Diseases” are written by individual NPRC Core Scientists who are experts in the specific subject of each article. Before publication on the website, each article is reviewed by representatives of all seven NPRCs.
David Abbott, Jordana Lenon and Jon Levine (WNPRC)
Polycystic ovary syndrome (PCOS) diminishes the quality of life of over 14 million women in the United States. A woman must have at least two of these traits to be diagnosed with PCOS: polycystic ovaries (a telltale “ring of pearls” grouping of small cysts within the ovaries), high testosterone or excess body hair, and intermittent or absent menstrual cycles. PCOS increases the risk of endometrial cancer, heart disease, high blood pressure, type 2 diabetes, asthma, obesity, depression and stress/anxiety, as well as infertility and a variety of reproductive disorders (1). Despite its prevalence, the syndrome was not well known or understood by the general public and the clinical community alike until the 2000s (2). With so many different symptoms, it took a long time for physicians to identify the disease as more than infertility. Women were being treated for diabetes, hirsutism, obesity and other clinical presentations, but not the underlying problem. PCOS is now known to be highly heritable (3), and prospective gene candidates are emerging (4), but progress towards a cure has been slowed because of the absence of a causal mechanism and a comprehensive animal model.
There is currently an intensive research effort underway to unravel the molecular origins of PCOS, with much progress being made through the study of female macaques, which can exhibit the syndrome in a manner strikingly similar to the disease in women (5, 6). In the past 20 years, NPRC scientists were the first to discover that, even though PCOS symptoms do not appear until puberty, the disease can be programmed in the fetus during the second trimester of pregnancy (7). Groundbreaking, carefully controlled studies showed how female offspring of pregnant rhesus monkeys exposed to male levels of testosterone, particularly during the second trimester, developed PCOS as adults. For the first time, scientists were able to glimpse a potential primary source of the problem: high testosterone early in gestation. More recent studies also associate early gestation testosterone exposure with naturally occurring PCOS-like traits in rhesus macaques.
NPRC researchers and clinicians have since been working together to obtain a basic scientific understanding of the disorder, and to apply their knowledge to clinical studies of women. Monkey studies implicate altered gene expression related to two gene candidates for PCOS in women, as well as dysfunctional fat storage, regulation of blood sugar by the pancreas and brain regulation of the menstrual cycle (8).
Today, thanks to research by NPRC scientists, many more clinicians cross-refer to one another, and catch more of the specific pathologies that can lead to a PCOS diagnosis. Clinicians and parents are engaging more lifestyle interventions at earlier ages than 15-20 years ago. Patients can better understand their affliction, learn what to expect from possible treatments, and realize that they have strong advocates who are working toward new therapies.
1. Hart R, Doherty DA. The potential implications of a PCOS diagnosis on a woman's long-term health using data linkage. J Clin Endocrinol Metab. 2015 Mar;100(3):911-9.
2. Conway G, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Franks S, Gambineri A, Kelestimur F, Macut D, Micic D, Pasquali R, Pfeifer M, Pignatelli D, Pugeat M, Yildiz BO; ESE PCOS Special Interest Group. The polycystic ovary syndrome: a position statement from the European Society of Endocrinology. Eur J Endocrinol. 2014 Oct;171(4):P1-29.
3. Kosova G, Urbanek M. Genetics of the polycystic ovary syndrome. Mol Cell Endocrinol. 2013 Jul 5;373(1-2):29-38. PubMed Central PMCID: PMC3609918
4. McAllister JM, Legro RS, Modi BP, Strauss JF 3rd. Functional genomics of PCOS: from GWAS to molecular mechanisms. Trends Endocrinol Metab. 2015 Mar;26(3):118-24. PubMed Central PMCID: PMC4346470
5. Arifin E, Shively CA, Register TC, Cline JM. Polycystic ovary syndrome with endometrial hyperplasia in a cynomolgus monkey (Macaca fascicularis). Vet Pathol. 2008 Jul;45(4):512-5.
6. Abbott DH, Nicol LE, Levine JE, Xu N, Goodarzi MO, Dumesic DA. Nonhuman primate models of polycystic ovary syndrome. Mol Cell Endocrinol. 2013 Jul 5;373(1-2):21-8. PubMed Central PMCID: PMC3683573
7. Abbott DH, Dumesic DA, Eisner JR, Colman RJ, Kemnitz JW. Insights into the development of polycystic ovary syndrome (PCOS) from studies of prenatally androgenized female rhesus monkeys. Trends Endocrinol Metab. 1998 Feb;9(2):62-7.
8. Abbott DH, Bacha F. Ontogeny of polycystic ovary syndrome and insulin resistance in utero and early childhood. Fertil Steril. 2013; 100(1):2-11. PubMed Central PMCID: PMC3732450
There are currently 31 publications available for Polycystic Ovary Syndrome.
Abbott DH, Vepraskas SH, Horton TH, Terasawa E, Levine JE
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.
Neuroendocrinology 2018 ; 107(2): 133-146.
Bishop CV, Mishler EC, Takahashi DL, Reiter TE, Bond KR, True CA, Slayden OD, Stouffer RL
Chronic hyperandrogenemia in the presence and absence of a western-style diet impairs ovarian and uterine structure/function in young adult rhesus monkeys.
Hum. Reprod. 2018 Jan; 33(1): 128-139.
Bishop CV, Stouffer RL, Takahashi DL, Mishler EC, Wilcox MC, Slayden OD, True CA
Chronic hyperandrogenemia and western-style diet beginning at puberty reduces fertility and increases metabolic dysfunction during pregnancy in young adult, female macaques.
Hum. Reprod. 2018 Feb; (): .
Guedikian AA, Lee AY, Grogan TR, Abbott DH, Largaespada K, Chazenbalk GD, Dumesic DA
Reproductive and metabolic determinants of granulosa cell dysfunction in normal-weight women with polycystic ovary syndrome.
Fertil. Steril. 2018 Feb; (): .
Abbott DH, Rayome BH, Dumesic DA, Lewis KC, Edwards AK, Wallen K, Wilson ME, Appt SE, Levine JE.
Clustering of PCOS-like traits in naturally hyperandrogenic female rhesus monkeys.
Hum. Reprod. 2017 Apr; 32(4): 923-936.
May 7th, 2012
Polycystic Ovary Syndrome: Lessons From Monkeys