Modeling perimenopause in sprague-dawley rats by chemical manipulation of the transition to ovarian failure

Jennifer B. Frye, Ashley L. Lukefahr, Laura Wright, Sam L. Marion, Patricia B. Hoyer, Janet L. Funk

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Various age-related diseases increase in incidence during perimenopause. However, our understanding of the effects of aging compared with hormonal changes of perimenopause in mediating these disease risks is incomplete, in part due to the lack of an experimental perimenopause model. We therefore aimed to determine whether manipulation of the transition to ovarian failure in rats via the use of 4-vinylcyclohexene diepoxide (VCD) could be used to model and accelerate hormonal changes characteristic of perimenopause. We examined long-term (11 to 20 mo), dose-dependent effects of VCD on reproductive function in 1- and 3-mo-old female Sprague-Dawley rats. Twenty-five daily doses of VCD (80 or 160 mg/kg daily compared with vehicle alone) depleted ovarian follicles in a dose-dependent fashion in rats of both ages, accelerated the onset of acyclicity, and caused dose-dependent increases in follicle-stimulating hormone that exceeded those naturally occurring with age in control rats but left serum levels of 17β-estradiol unchanged, with continued ovarian production of androstenedione. High-dose VCD caused considerable nonovarian toxicities in 3-mo-old Sprague-Dawley rats, making this an unsuitable model. In contrast, 1-mo-old rats had more robust dose-dependent increases in follicle-stimulating hormone without evidence of systemic toxicity in response to either VCD dose. Because perimenopause is characterized by an increase in follicle-stimulating hormone with continued secretion of ovarian steroids, VCD acceleration of an analogous hormonal milieu in 1-mo-old Sprague-Dawley rats may be useful for probing the hormonal effects of perimenopause on age-related disease risk.

Original languageEnglish (US)
Pages (from-to)193-202
Number of pages10
JournalComparative Medicine
Volume62
Issue number3
StatePublished - Jun 2012
Externally publishedYes

Fingerprint

Perimenopause
Sprague Dawley Rats
Rats
rats
Follicle Stimulating Hormone
dosage
follicle-stimulating hormone
Toxicity
Rat control
Ovarian Follicle
toxicity
Androstenedione
androstenedione
Age of Onset
ovarian follicles
4-vinyl-1-cyclohexene dioxide
Estradiol
Theoretical Models
steroids
Aging of materials

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • veterinary(all)

Cite this

Frye, J. B., Lukefahr, A. L., Wright, L., Marion, S. L., Hoyer, P. B., & Funk, J. L. (2012). Modeling perimenopause in sprague-dawley rats by chemical manipulation of the transition to ovarian failure. Comparative Medicine, 62(3), 193-202.

Modeling perimenopause in sprague-dawley rats by chemical manipulation of the transition to ovarian failure. / Frye, Jennifer B.; Lukefahr, Ashley L.; Wright, Laura; Marion, Sam L.; Hoyer, Patricia B.; Funk, Janet L.

In: Comparative Medicine, Vol. 62, No. 3, 06.2012, p. 193-202.

Research output: Contribution to journalArticle

Frye, JB, Lukefahr, AL, Wright, L, Marion, SL, Hoyer, PB & Funk, JL 2012, 'Modeling perimenopause in sprague-dawley rats by chemical manipulation of the transition to ovarian failure', Comparative Medicine, vol. 62, no. 3, pp. 193-202.
Frye, Jennifer B. ; Lukefahr, Ashley L. ; Wright, Laura ; Marion, Sam L. ; Hoyer, Patricia B. ; Funk, Janet L. / Modeling perimenopause in sprague-dawley rats by chemical manipulation of the transition to ovarian failure. In: Comparative Medicine. 2012 ; Vol. 62, No. 3. pp. 193-202.
@article{09d79fa869424bbb9c3a28b6924fa839,
title = "Modeling perimenopause in sprague-dawley rats by chemical manipulation of the transition to ovarian failure",
abstract = "Various age-related diseases increase in incidence during perimenopause. However, our understanding of the effects of aging compared with hormonal changes of perimenopause in mediating these disease risks is incomplete, in part due to the lack of an experimental perimenopause model. We therefore aimed to determine whether manipulation of the transition to ovarian failure in rats via the use of 4-vinylcyclohexene diepoxide (VCD) could be used to model and accelerate hormonal changes characteristic of perimenopause. We examined long-term (11 to 20 mo), dose-dependent effects of VCD on reproductive function in 1- and 3-mo-old female Sprague-Dawley rats. Twenty-five daily doses of VCD (80 or 160 mg/kg daily compared with vehicle alone) depleted ovarian follicles in a dose-dependent fashion in rats of both ages, accelerated the onset of acyclicity, and caused dose-dependent increases in follicle-stimulating hormone that exceeded those naturally occurring with age in control rats but left serum levels of 17β-estradiol unchanged, with continued ovarian production of androstenedione. High-dose VCD caused considerable nonovarian toxicities in 3-mo-old Sprague-Dawley rats, making this an unsuitable model. In contrast, 1-mo-old rats had more robust dose-dependent increases in follicle-stimulating hormone without evidence of systemic toxicity in response to either VCD dose. Because perimenopause is characterized by an increase in follicle-stimulating hormone with continued secretion of ovarian steroids, VCD acceleration of an analogous hormonal milieu in 1-mo-old Sprague-Dawley rats may be useful for probing the hormonal effects of perimenopause on age-related disease risk.",
author = "Frye, {Jennifer B.} and Lukefahr, {Ashley L.} and Laura Wright and Marion, {Sam L.} and Hoyer, {Patricia B.} and Funk, {Janet L.}",
year = "2012",
month = "6",
language = "English (US)",
volume = "62",
pages = "193--202",
journal = "Comparative Medicine",
issn = "1532-0820",
publisher = "American Association for Laboratory Animal Science",
number = "3",

}

TY - JOUR

T1 - Modeling perimenopause in sprague-dawley rats by chemical manipulation of the transition to ovarian failure

AU - Frye, Jennifer B.

AU - Lukefahr, Ashley L.

AU - Wright, Laura

AU - Marion, Sam L.

AU - Hoyer, Patricia B.

AU - Funk, Janet L.

PY - 2012/6

Y1 - 2012/6

N2 - Various age-related diseases increase in incidence during perimenopause. However, our understanding of the effects of aging compared with hormonal changes of perimenopause in mediating these disease risks is incomplete, in part due to the lack of an experimental perimenopause model. We therefore aimed to determine whether manipulation of the transition to ovarian failure in rats via the use of 4-vinylcyclohexene diepoxide (VCD) could be used to model and accelerate hormonal changes characteristic of perimenopause. We examined long-term (11 to 20 mo), dose-dependent effects of VCD on reproductive function in 1- and 3-mo-old female Sprague-Dawley rats. Twenty-five daily doses of VCD (80 or 160 mg/kg daily compared with vehicle alone) depleted ovarian follicles in a dose-dependent fashion in rats of both ages, accelerated the onset of acyclicity, and caused dose-dependent increases in follicle-stimulating hormone that exceeded those naturally occurring with age in control rats but left serum levels of 17β-estradiol unchanged, with continued ovarian production of androstenedione. High-dose VCD caused considerable nonovarian toxicities in 3-mo-old Sprague-Dawley rats, making this an unsuitable model. In contrast, 1-mo-old rats had more robust dose-dependent increases in follicle-stimulating hormone without evidence of systemic toxicity in response to either VCD dose. Because perimenopause is characterized by an increase in follicle-stimulating hormone with continued secretion of ovarian steroids, VCD acceleration of an analogous hormonal milieu in 1-mo-old Sprague-Dawley rats may be useful for probing the hormonal effects of perimenopause on age-related disease risk.

AB - Various age-related diseases increase in incidence during perimenopause. However, our understanding of the effects of aging compared with hormonal changes of perimenopause in mediating these disease risks is incomplete, in part due to the lack of an experimental perimenopause model. We therefore aimed to determine whether manipulation of the transition to ovarian failure in rats via the use of 4-vinylcyclohexene diepoxide (VCD) could be used to model and accelerate hormonal changes characteristic of perimenopause. We examined long-term (11 to 20 mo), dose-dependent effects of VCD on reproductive function in 1- and 3-mo-old female Sprague-Dawley rats. Twenty-five daily doses of VCD (80 or 160 mg/kg daily compared with vehicle alone) depleted ovarian follicles in a dose-dependent fashion in rats of both ages, accelerated the onset of acyclicity, and caused dose-dependent increases in follicle-stimulating hormone that exceeded those naturally occurring with age in control rats but left serum levels of 17β-estradiol unchanged, with continued ovarian production of androstenedione. High-dose VCD caused considerable nonovarian toxicities in 3-mo-old Sprague-Dawley rats, making this an unsuitable model. In contrast, 1-mo-old rats had more robust dose-dependent increases in follicle-stimulating hormone without evidence of systemic toxicity in response to either VCD dose. Because perimenopause is characterized by an increase in follicle-stimulating hormone with continued secretion of ovarian steroids, VCD acceleration of an analogous hormonal milieu in 1-mo-old Sprague-Dawley rats may be useful for probing the hormonal effects of perimenopause on age-related disease risk.

UR - http://www.scopus.com/inward/record.url?scp=84868298229&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84868298229&partnerID=8YFLogxK

M3 - Article

VL - 62

SP - 193

EP - 202

JO - Comparative Medicine

JF - Comparative Medicine

SN - 1532-0820

IS - 3

ER -