Terms such as quiescent, inhibited, and inactive are often used to describe the state of the ovaries in seasonally breeding mammals when considered outside of the breeding season. However, recent findings have demonstrated important structural and functional changes in the so-called quiescent ovary that appear to modulate the reproductive aging process. More specifically, maintaining female Siberian hamsters in short photoperiod is associated with profound changes of the ovary that appear to manifest as decelerated reproductive aging. The outcomes of the short-day-induced changes include improved fertility and a preservation of ovarian follicles in older females. Therefore, the cessation of ovulatory activity under conditions that do not favor breeding should not be equated with ovarian inactivity. This research project will transform and inform our thinking about the seasonally quiescent ovary and provide a better understanding of its role in reproductive aging. Integrative analyses will determine if and how photoperiod-induced changes in hormone secretion from the pituitary gland contribute to the development of the short-day ovarian phenotype. Because melatonin, a hormone secreted by the pineal gland, mediates the effects of short photoperiod in seasonally breeding mammals, research will determine if the absence of melatonin is associated with an acceleration of ovarian aging. The broader impact of this research lies in its inclusion of trainees in all aspects of the investigation, with a special effort made to attract women and underrepresented minorities to the lab. The results of our experiments will be of interest to a broad array of scientists, including reproductive biologists, ecologists, chronobiologists, and gerontologists. Because there is a continuing trend for women to delay having their first child until an advanced reproductive age, our results may have important implications for society, as insights into female reproductive aging may be applicable to all mammalian species, including our own.

Project Report

Terms such as quiescent, inhibited, and inactive are often used to describe the state of the ovaries when seasonally breeding mammals are evaluated outside of the breeding season. However, recent findings from the principal investigator’s laboratory have demonstrated important structural and functional changes in the so-called quiescent ovary that appear to modulate the reproductive aging process. The animal model we use to study female reproductive aging is the Siberian hamster, because the reproductive physiology of this species is profoundly affected by changes in day length. More specifically, maintaining a female Siberian hamster in short, winter-like day lengths is associated with substantial morphological, physiological, and biochemical changes of the ovary that appear to manifest as decelerated reproductive aging. Like most mammals, the Siberian hamster uses the hormone melatonin, secreted from the pineal gland, as the biochemical signal that conveys information about changing day length. The outcomes of the short-day-induced changes include improved fertility and fecundity and a larger reserve of ovarian follicles in older females as compared to hamsters held in long days. Therefore, the cessation of ovulatory activity under conditions that do not favor breeding should not be equated with ovarian inactivity. Intellectual Merit: The completed research informed our thinking about the seasonally quiescent ovary, and it provides a better understanding of its role in reproductive aging. We pursued two major areas of investigation: 1. Knowing that follicle stimulating hormone (FSH) is decreased in hamsters held in short days, we experimentally increased FSH in short days and suppressed it in long days. These mismatches of day length and FSH demonstrated that suppression of this hormone is necessary, but not sufficient to induce changes in the ovary that mimic the changes caused by short days. Thus, we expect other hormonal changes induced by short days, such as decreased prolactin or increased melatonin, combine with decreased FSH to bring about the ovarian changes that ultimately lead to decelerated reproductive aging. These findings are the subject of a manuscript that was recently submitted for publication, and a revision is now under review. The postdoctoral associate who trained under this award also presented her results to a broad audience of scientists at the 2012 Meeting of the Society for Integrative and Comparative Biology. 2. Our prior investigations suggested that female reproductive aging is accelerated by the absence of melatonin in Siberian hamsters. To thoroughly test this hypothesis, we surgically removed the pineal gland (the principal source of melatonin) from three-day-old hamsters and evaluated their fertility and fecundity at six months of age. With larger sample sizes than our prior investigation, we did not find convincing evidence to support the hypothesis that postnatal absence of melatonin causes accelerated reproductive aging. The broader impact of this proposal lies in its inclusion of trainees in all aspects of the research, with a special effort made to attract women and underrepresented minorities to my lab. The award directly supported a postdoctoral associate, and indirectly supported nine undergraduate researchers, all of whom are women. During this award, the postdoctoral associate has contributed to an educational outreach program at the local science center, where she teaches pre- and elementary school students about adaptions that animals use to survive harsh winter conditions, using Siberian hamsters as an informative model. The results of our experiments will be of interest to a broad array of scientists, including reproductive biologists, ecologists, chronobiologists, and gerontologists. Because there is a continuing trend for women to delay having their first child until an advanced reproductive age, our results may have important implications for society, as insights into female reproductive aging may be applicable to all mammalian species, including our own.

Agency
National Science Foundation (NSF)
Institute
Division of Integrative Organismal Systems (IOS)
Type
Standard Grant (Standard)
Application #
0950650
Program Officer
Steven Ellis
Project Start
Project End
Budget Start
2010-05-01
Budget End
2012-04-30
Support Year
Fiscal Year
2009
Total Cost
$246,773
Indirect Cost
Name
Cornell Univ - State: Awds Made Prior May 2010
Department
Type
DUNS #
City
Ithica
State
NY
Country
United States
Zip Code
14850