With aging, female rats exhibit a gradual loss of regular estrous cyclicity and decline in fertility (% of females with successful pregnancy) and fecundity (litter size). Our studies have provided evidence suggesting reproductive decline in aging female rats caused by pre-implantation failures and/or early post-implantation losses. Among the factors which influnce successful implantation during early gestation are the ovulation of healthy occytes, successful fertilization and development of these zygotes, and appropriate hormonal support for blastocyst development and implantation. This grant proposal outlines systematic approaches: 1) to examine the oocyte quality by assessing its cell viability, protein composition and fertilization rate in 4- to 14-month-old rats displaying regular estrous cyclicity, irregular estrous cyclicity, or persistent estrus (resulting from chronic anovulation); 2) to assess the cell viability and protein composition of developing embryos during Days 2-5 of pregnancy; 3) to examine the effects of aging and estrous cycle patterns on early embryonic development, and to determine the relation of plasma prolactin, progesterone and estradiol levels to blastocyst development and implantation success; 4) to determine the specific effects of estrous cycle patterns on reproductive function in aging female rats following experimental manipulations and a transient resumption of regular estrous cyclicity; 5) to examine the effects of progesterone-treatment early in life on subsequent oocyte quality, and on the patterns of embryonic development and hormone secretion during early pregnancy. The overall objective of this grant proposal is to understand the potential impact of ovarian and plasma progesterone and estradiol levels (as influenced by prolactin and gonadotropins) on folliculogenesis, oocyte and zygote quality, blastocyst development and implantation success in aging female rats displaying different estrous cycle patterns. We believe that the information gained from these proposed studies will provide important foundation for understanding the hormonal regulation of oocyte maturation, early embryogenesis, and blastocyst implantation in mammals. Such findings may be relevant to human reproduction, particularly for the in vitro fertilization and embryo transfer programs.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
3R37AG004810-13S2
Application #
2800971
Study Section
Special Emphasis Panel (NSS)
Project Start
1984-04-01
Project End
1999-03-31
Budget Start
1998-06-15
Budget End
1999-03-31
Support Year
13
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Tsai, Houng-Wei; LaPolt, Philip S; Olcott, Angelica P et al. (2004) Temporal changes occur in the neuroendocrine control of gonadotropin secretion in aging female rats: role of progesterone. Biol Reprod 71:845-52
Anzalone, C R; Hong, L S; Lu, J K et al. (2001) Influences of age and ovarian follicular reserve on estrous cycle patterns, ovulation, and hormone secretion in the Long-Evans rat. Biol Reprod 64:1056-62
LaPolt, P S; Lu, J K (2001) Effects of aging on luteinizing hormone secretion, ovulation, and ovarian tissue-type plasminogen activator expression. Exp Biol Med (Maywood) 226:127-32
LaPolt, P S; Matt, D W; Lu, J K (1998) Progesterone implants delay age-related declines in regular estrous cyclicity and the ovarian follicular reserve in Long-Evans rats. Biol Reprod 59:197-201
Anzalone, C R; Lu, J K; LaPolt, P S (1998) Influences of age and reproductive status on ovarian ovulatory responsiveness to gonadotropin stimulation. Proc Soc Exp Biol Med 217:455-60
Matt, D W; Sayles, T E; Jih, M H et al. (1993) Alterations in the postovariectomy increases in gonadotropin secretion in middle-aged persistent-estrous rats: correlation with pituitary gonadotropin subunit gene expression. Neuroendocrinology 57:351-8
Jih, M H; Lu, J K; Wan, Y J et al. (1993) Inhibin subunit gene expression and distribution in the ovaries of immature, young adult, middle-aged, and old female rats. Endocrinology 132:319-26
Jih, M H; Lu, J K; Wan, Y J et al. (1993) Enhanced ovarian inhibin subunit gene expression in aging rats is due to chronic anovulation. Biol Reprod 49:1208-14
Day, J R; Lapolt, P S; Lu, J K (1991) Plasma patterns of prolactin, progesterone, and estradiol during early pregnancy in aging rats: relation to embryonic development. Biol Reprod 44:786-90
LaPolt, P S; Day, J R; Lu, J K (1990) Effects of estradiol and progesterone on early embryonic development in aging rats. Biol Reprod 43:843-50

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