Fetal, infant, adolescent and adult phenotypes of polycystic ovary syndrome in prenatally androgenized female rhesus monkeys

David H. Abbott, Alice F Tarantal, Daniel A. Dumesic

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Old World monkeys provide naturally occurring and experimentally induced phenotypes closely resembling the highly prevalent polycystic ovary syndrome (PCOS) in women. In particular, experimentally induced fetal androgen excess in female rhesus monkeys produces a comprehensive adult PCOS-like phenotype that includes both reproductive and metabolic dysfunction found in PCOS women. Such a reliable experimental approach enables the use of the prenatally androgenized (PA) female rhesus monkey model to (1) examine fetal, infant and adolescent antecedents of adult pathophysiology, gaining valuable insight into early phenotypic expression of PCOS, and (2) to understand adult pathophysiology from a mechanistic perspective. Elevated circulating luteinizing hormone (LH) levels are the earliest indication of reproductive dysfunction in late gestation nonhuman primate fetuses and infants exposed to androgen excess during early (late first to second trimester) gestation. Such early gestation-exposed PA infants also are hyperandrogenic, with both LH hypersecretion and hyperandrogenism persisting in early gestation-exposed PA adults. Similarly, subtle metabolic abnormalities appearing in young nonhuman primate infants and adolescents precede the abdominal adiposity, hyperliplidemia and increased incidence of type 2 diabetes that characterize early gestationexposed PA adults. These new insights into the developmental origins of PCOS, and progression of the pathophysiology from infancy to adulthood, provide opportunities for clinical intervention to ameliorate the PCOS phenotype thus providing a preventive health-care approach to PCOS-related abnormalities. For example, PCOS-like traits in PA monkeys, as in PCOS women, can improve with better insulin-glucose homeostasis, suggesting that lifestyle interventions preventing increased adiposity in adolescent daughters of PCOS mothers also may reduce their risk of acquiring many PCOS-related metabolic abnormalities in adulthood.

Original languageEnglish (US)
Pages (from-to)776-784
Number of pages9
JournalAmerican Journal of Primatology
Volume71
Issue number9
DOIs
StatePublished - Sep 2009

Fingerprint

polycystic ovary syndrome
Macaca mulatta
phenotype
pregnancy
abnormality
androgen
primate
hormone
pathophysiology
diabetes
homeostasis
adiposity
lifestyle
luteinizing hormone
androgens
health care
adulthood
glucose
Primates
infant

Keywords

  • Androgen excess
  • Anovulation
  • Fetal programming
  • Insulin resistance
  • LH hypersecretion
  • Obesity
  • PCOS-associated male phenotype

ASJC Scopus subject areas

  • Animal Science and Zoology
  • Ecology, Evolution, Behavior and Systematics

Cite this

Fetal, infant, adolescent and adult phenotypes of polycystic ovary syndrome in prenatally androgenized female rhesus monkeys. / Abbott, David H.; Tarantal, Alice F; Dumesic, Daniel A.

In: American Journal of Primatology, Vol. 71, No. 9, 09.2009, p. 776-784.

Research output: Contribution to journalArticle

@article{22118fa24c154c769ba65b7cc0eee6d7,
title = "Fetal, infant, adolescent and adult phenotypes of polycystic ovary syndrome in prenatally androgenized female rhesus monkeys",
abstract = "Old World monkeys provide naturally occurring and experimentally induced phenotypes closely resembling the highly prevalent polycystic ovary syndrome (PCOS) in women. In particular, experimentally induced fetal androgen excess in female rhesus monkeys produces a comprehensive adult PCOS-like phenotype that includes both reproductive and metabolic dysfunction found in PCOS women. Such a reliable experimental approach enables the use of the prenatally androgenized (PA) female rhesus monkey model to (1) examine fetal, infant and adolescent antecedents of adult pathophysiology, gaining valuable insight into early phenotypic expression of PCOS, and (2) to understand adult pathophysiology from a mechanistic perspective. Elevated circulating luteinizing hormone (LH) levels are the earliest indication of reproductive dysfunction in late gestation nonhuman primate fetuses and infants exposed to androgen excess during early (late first to second trimester) gestation. Such early gestation-exposed PA infants also are hyperandrogenic, with both LH hypersecretion and hyperandrogenism persisting in early gestation-exposed PA adults. Similarly, subtle metabolic abnormalities appearing in young nonhuman primate infants and adolescents precede the abdominal adiposity, hyperliplidemia and increased incidence of type 2 diabetes that characterize early gestationexposed PA adults. These new insights into the developmental origins of PCOS, and progression of the pathophysiology from infancy to adulthood, provide opportunities for clinical intervention to ameliorate the PCOS phenotype thus providing a preventive health-care approach to PCOS-related abnormalities. For example, PCOS-like traits in PA monkeys, as in PCOS women, can improve with better insulin-glucose homeostasis, suggesting that lifestyle interventions preventing increased adiposity in adolescent daughters of PCOS mothers also may reduce their risk of acquiring many PCOS-related metabolic abnormalities in adulthood.",
keywords = "Androgen excess, Anovulation, Fetal programming, Insulin resistance, LH hypersecretion, Obesity, PCOS-associated male phenotype",
author = "Abbott, {David H.} and Tarantal, {Alice F} and Dumesic, {Daniel A.}",
year = "2009",
month = "9",
doi = "10.1002/ajp.20679",
language = "English (US)",
volume = "71",
pages = "776--784",
journal = "American Journal of Primatology",
issn = "0275-2565",
publisher = "John Wiley and Sons Inc.",
number = "9",

}

TY - JOUR

T1 - Fetal, infant, adolescent and adult phenotypes of polycystic ovary syndrome in prenatally androgenized female rhesus monkeys

AU - Abbott, David H.

AU - Tarantal, Alice F

AU - Dumesic, Daniel A.

PY - 2009/9

Y1 - 2009/9

N2 - Old World monkeys provide naturally occurring and experimentally induced phenotypes closely resembling the highly prevalent polycystic ovary syndrome (PCOS) in women. In particular, experimentally induced fetal androgen excess in female rhesus monkeys produces a comprehensive adult PCOS-like phenotype that includes both reproductive and metabolic dysfunction found in PCOS women. Such a reliable experimental approach enables the use of the prenatally androgenized (PA) female rhesus monkey model to (1) examine fetal, infant and adolescent antecedents of adult pathophysiology, gaining valuable insight into early phenotypic expression of PCOS, and (2) to understand adult pathophysiology from a mechanistic perspective. Elevated circulating luteinizing hormone (LH) levels are the earliest indication of reproductive dysfunction in late gestation nonhuman primate fetuses and infants exposed to androgen excess during early (late first to second trimester) gestation. Such early gestation-exposed PA infants also are hyperandrogenic, with both LH hypersecretion and hyperandrogenism persisting in early gestation-exposed PA adults. Similarly, subtle metabolic abnormalities appearing in young nonhuman primate infants and adolescents precede the abdominal adiposity, hyperliplidemia and increased incidence of type 2 diabetes that characterize early gestationexposed PA adults. These new insights into the developmental origins of PCOS, and progression of the pathophysiology from infancy to adulthood, provide opportunities for clinical intervention to ameliorate the PCOS phenotype thus providing a preventive health-care approach to PCOS-related abnormalities. For example, PCOS-like traits in PA monkeys, as in PCOS women, can improve with better insulin-glucose homeostasis, suggesting that lifestyle interventions preventing increased adiposity in adolescent daughters of PCOS mothers also may reduce their risk of acquiring many PCOS-related metabolic abnormalities in adulthood.

AB - Old World monkeys provide naturally occurring and experimentally induced phenotypes closely resembling the highly prevalent polycystic ovary syndrome (PCOS) in women. In particular, experimentally induced fetal androgen excess in female rhesus monkeys produces a comprehensive adult PCOS-like phenotype that includes both reproductive and metabolic dysfunction found in PCOS women. Such a reliable experimental approach enables the use of the prenatally androgenized (PA) female rhesus monkey model to (1) examine fetal, infant and adolescent antecedents of adult pathophysiology, gaining valuable insight into early phenotypic expression of PCOS, and (2) to understand adult pathophysiology from a mechanistic perspective. Elevated circulating luteinizing hormone (LH) levels are the earliest indication of reproductive dysfunction in late gestation nonhuman primate fetuses and infants exposed to androgen excess during early (late first to second trimester) gestation. Such early gestation-exposed PA infants also are hyperandrogenic, with both LH hypersecretion and hyperandrogenism persisting in early gestation-exposed PA adults. Similarly, subtle metabolic abnormalities appearing in young nonhuman primate infants and adolescents precede the abdominal adiposity, hyperliplidemia and increased incidence of type 2 diabetes that characterize early gestationexposed PA adults. These new insights into the developmental origins of PCOS, and progression of the pathophysiology from infancy to adulthood, provide opportunities for clinical intervention to ameliorate the PCOS phenotype thus providing a preventive health-care approach to PCOS-related abnormalities. For example, PCOS-like traits in PA monkeys, as in PCOS women, can improve with better insulin-glucose homeostasis, suggesting that lifestyle interventions preventing increased adiposity in adolescent daughters of PCOS mothers also may reduce their risk of acquiring many PCOS-related metabolic abnormalities in adulthood.

KW - Androgen excess

KW - Anovulation

KW - Fetal programming

KW - Insulin resistance

KW - LH hypersecretion

KW - Obesity

KW - PCOS-associated male phenotype

UR - http://www.scopus.com/inward/record.url?scp=69349084968&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69349084968&partnerID=8YFLogxK

U2 - 10.1002/ajp.20679

DO - 10.1002/ajp.20679

M3 - Article

C2 - 19367587

AN - SCOPUS:69349084968

VL - 71

SP - 776

EP - 784

JO - American Journal of Primatology

JF - American Journal of Primatology

SN - 0275-2565

IS - 9

ER -