The reproductive neuroendocrine axis of the female undergoes well described age-related changes which result in the loss of cyclicity during middle age. We have recently shown that adult females exposed to ethanol while in utero exhibit regular estrous cyclicity following puberty but become acyclic at a much earlier age than control females. Studies in this rat model have demonstrated that fetal exposure to ethanol will disrupt the hypothalamo-pituitary-gonadal axis of the adult female. Adult fetal alcohol exposed (FAE) females exhibit a delay in the onset of puberty, reductions in the preovulatory-like surge of anterior pituitary gonadotropic hormones, reductions in anterior pituitary gonadotropin subunit mRNAs and reductions in gonadotropin-releasing hormone mRNA in a specific population of neurons in the basal forebrain. These data demonstrate that the young adult FAE female exhibits neuroendocrine impairments which can limit reproductive potential. Many of the neuroendocrine changes in young adult FAE females are similar to those described for the normal middle-aged female rat immediately prior to the onset of age-related anovulatory sterility. Thus, it appears that the FAE female is at increased risk to enter reproductive senescence at an early age. The elucidation of the consequences of fetal alcohol exposure on reproductive hormone secretion supports the possibility of a heightened risk of an early age-related loss of cyclicity in adult human female populations, not limited to those diagnosed with fetal alcohol syndrome, but including populations exposed to much more modest levels of ethanol in utero. In this proposal, we outline studies to investigate the neuroendocrine mechanisms which underlie the deficits in hypothalamo-pituitary-gonadal function and the early onset of anovulatory sterility in the adult female rat exposed to alcohol in utero. We hypothesize that hormone secretion in adult FAE females is impaired due to the decrease in hypothalamic release of gonadotropin-releasing hormone. This is a consequence of the loss of neural systems driving GnRH synthesis or secretion. The long-term goals of these studies are to define the neuroendocrine mechanisms which regulate age-related reproductive deficits in adult females especially in terms of those which are susceptible to damage by prenatal exposure to teratogenic agents such as alcohol.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA012693-03
Application #
6509381
Study Section
Alcohol and Toxicology Subcommittee 4 (ALTX)
Program Officer
Foudin, Laurie L
Project Start
2000-03-01
Project End
2004-02-29
Budget Start
2002-03-01
Budget End
2003-02-28
Support Year
3
Fiscal Year
2002
Total Cost
$290,000
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Microbiology/Immun/Virology
Type
Schools of Veterinary Medicine
DUNS #
112617480
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
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