Free Access
Reprod. Nutr. Dev.
Volume 45, Number 2, March-April 2005
Page(s) 143 - 150
Reprod. Nutr. Dev. 45 (2005) 143-150
DOI: 10.1051/rnd:2005011

Declining fertility in the lethal yellow mouse is related to progressive hyperleptinemia and leptin resistance

John D. Branniana, Gina M. Furmanb and Maureen Digginsb

a  Department of Obstetrics and Gynecology, University of South Dakota, School of Medicine Sioux Falls, SD, USA
b  Department of Biology, Augustana College, Sioux Falls, SD, USA

(Received 26 October 2004; accepted 6 December 2004)

Abstract - Mice possessing the lethal yellow mutation (C57BL/6J Ay/a) become obese and develop hyperleptinemia and leptin resistance as they age. To determine the relationship between altered leptin physiology and reproductive function in these mice, we compared body weight (BW), serum leptin concentration, ovulation rate, and in vitro blastocyst development among 120- and 180-d-old lethal yellow and black non-mutant (a/a) mice. Estrous female yellow and black mice were mated with fertile black males. Oviducts were flushed ~ 36 h after mating and the recovered embryos were cultured for 96 h. BW, serum leptin levels, and the leptin:BW ratio differed among groups as follows: 180-d yellow > 120-d yellow > 180-d black = 120-d black. Ovulation rate was similar among 120-d yellow and black, and 180-d black mice. Among 180-d yellow mice, five of twelve mice failed to ovulate, but the other seven mice ovulated a similar number of oocytes as their black counterparts (8.4 ± 0.9 versus 8.0 ± 1.3). Non-ovulators had higher (P < 0.05) leptin levels (56.6 ± 1.8 ng·mL-1) than ovulators (46.2 ± 3.5), but BW did not differ significantly. Fewer embryos from 180-d yellow mice reached the blastocyst stage in culture than did the embryos from black mice (55% versus 83%, P < 0.05). Moreover, blastocyst development in 180-d old yellow mice negatively correlated with leptin levels (r = -0.797, P = 0.032) and leptin:BW ratio (r = -0.847, P = 0.016), but not with BW. Declining reproductive function in lethal yellow mice appears to be related to increasing levels of leptin and progression of leptin resistance.

Key words: obesity / leptin / agouti / reproduction

Corresponding author: John D. Brannian

© INRA, EDP Sciences 2005