Dr. Maureen Diggins-Hutcheson
Professor Emerita, Reproductive Biology
2001 S. Summit Ave.
Sioux Falls, SD 57197
Toll-Free 800.727.2844 ext. 4809
Ph.D. Northwestern University, 1971
M.S. Northwestern University, 1968
B.A. Mount Marty College, 1967
For our research on body fat and fertility, we use the lethal yellow mouse mutant. The gene, found at the agouti locus on chromosome 2, is lethal in the homozygous condition. Heterozygous mice live but exhibit a collection of characteristics referred to as the lethal yellow syndrome. The LYS includes yellow coat color, obesity, hyperglycemia, insulin resistance, infertility, and leptin resistance. Our main focus is on the link between increasing obesity and declining fertility seen in this model.
Leptin is a hormone produced by fat cells which acts upon the hypothalamus of the brain and affects eating behavior, body weight, and reproduction. Leptin provides a significant link between metabolic state and fertility. A minimum level of leptin appears to be necessary for secretion of GnRH, FSH, and LH and, hence, for fertility. However, excess leptin, due to excess body fat, may result in decreased fertility.
Recent evidence demonstrates direct regulation by leptin on target cells in the ovary, corpora lutea, and the oocytes themselves in addition to effects on the hypothalamus. Again, a minimum level of leptin appears necessary for successful ovarian function; but excess leptin, as in severe obesity, may lead to a state of leptin resistance and declining fertility.
To examine the relationship between the potential leptin resistance in these mice and their declining fertility with increasing weight, we study such things as serum leptin concentration, ovulation rate, development of embryos in vitro, effects of leptin on vascularization in ovarian tissues, and other manifestations of leptin and leptin resistance in reproductive tissues of these mice. Our hypothesis is that declining reproductive function may be directly related to progression of leptin resistance associated with obesity.
This is a picture of newly ovulated mouse eggs which have been extracted from the Fallopian tubes. We have studied the decline in fertility found in obese yellow mice by examining mating success, ovulation rates, and pregnancy rates. We have also examined serum levels of follicle stimulating hormone (FSH) and estrogens. Although FSH levels are depressed in obese mice, estrogens are elevated. Estrogens, especially estrone from fat cells, may be exerting negative feedback effects on the hypothalamic-pituitary-ovarian system and depressing ovulation and thus fertility.
Brannian, J.D., G.M. Furman, M. Diggins, 2005. Declining fertility in the lethal yellow mouse is related to progressive hyperleptinemia and leptin resistance. Reprod. Nutr. Dev. 45:143-150.
Diggins, M.R., G. Furman, H. Reber, and N.H. Granholm, 2003. Body weight, serum leptin, and ovulation rates in lethal y ellow and mahogany mice. Proc. S.D. Acad. Sci., 82:309.
Oberg, Trynda N., Nels H. Granholm, and Maureen R. Diggins. 2002. Effects of Lethal Yellow and Mahogany Mutations on Reporduction in Female Mice. Proc. S.D. Acad. Sci., 81:275.
Diggins, M.R., M. Cederburg, T. Dierks, and N.H. Granholm, 2001. Obesity and infertility in the Lethal Yellow Mouse model--Does the mutant gene directly affect Fertility? Proc. S.D. Acad. Sci., 80:413.
Diggins, M.R., J. Spiry, and N.H. Granholm. 2000. Measurement of estrone and progesterone in mouse serum using enzyme linked immunoassays. Proc. S.D. Acad. Sci., 79:133.
Diggins, M.R., R.C. Christopher, and N.H. Granholm. 1999. Body weight and ovarian function in Ay/a mice. Proc. S.D. Acad. Sci., 78:215-216.
Dickens, G.A., M.R. Diggins, and N.H. Granholm. 1998. Separation of maternal and embryo contributions to reproductive failure in yellow mice (Ay/a; C57BL/6J). Proc. S.D. Acad. Sci., 77:99.
Monroe, D.G., Wipf, L.P., Diggins, M.R., Matthees, D.P., and Granholm, N.H. 1998. Agouti-related maturation and tissue distribution of alpha-Melanocyte Stimulating Hormone in wild-type (AwJ/AwJ) and mutant (Ay/a, a/a) mice. Pigment Cell Res. 11:310-313.
Diggins, M.R., D. Dierks, J. Spiry, and N.H. Granholm. 1997. Serum estradiol levels in the lethal yellow mouse. Proc. S.D. Acad. Sci., 76:297-298.
Diggins, M.R., R.R. Rowland, and N.H. Granholm. 1996. In situ hybridization for expression of the agouti gene in tissues of the lethal yellow mouse. Proc. S.D. Acad. Sci., 75:215.
Diggins, M.R., M.D. Johansen, R.R. Rowland, and N.H. Granholm. 1996. Agouti gene expression in adipocytes of mice and agouti gene identification in cattle. Pigment Cell Res.
Grants and Projects
National Institute of Health, InBRE Grant #2P20RR16479-04, SD Biomedical Research Infrastructure Network to USD School of Medicine, Maureen Diggins, Program Coordinator, $16 million, 2004-2009.
National Institutes of Health, AREA Grant # 1R15 HDO44438-01. Leptin Resistance and Ovarian Function in Mice ($122,500), Maureen Diggins, P.I., 2003-2005.
Ethel Austin Martin Foundation. Obesity and Infertility: The Relationship of Body Fat and Fertility ($15,000), Maureen Diggins and Nels Granholm, 1999.
National Science Foundation, MRI Grant #DBI-9871401. Acquisition of Data Analysis Instrumentation for Biological Research and Undergraduate Training at Augustana College ($35,960), Debra Carlson, Micheal Wanous, and Maureen Diggins, 1998.
U.S. Dept. of Agriculture Grant #95-37208-2245. Genetically Induced Obesity and Decreased Reproductive Efficiency ($57,530), Maureen Diggins, 1995-97.
National Science Foundation, REU Grant #BIR-9300418, Stable Isotopic Applications to Great Plains Ecology, Paleoecology, Archeology, and Physiology ($54,000), Larry Tieszen and Maureen Diggins, 1993.
National Science Foundation, REU Grant #BIO-9200345, Stable Isotopic Applications to Great Plains Ecology, Paleoecology, Archeology, and Physiology ($50,000), Larry Tieszen and Maureen Diggins, 1992.
National Institutes of Health, AREA Grant # 1 R15 HD26929-01A1, Obesity and Infertility in the Lethal Yellow Mouse ($63,693), Maureen Diggins, P.I., 1991-93.