Leptin requirement for conception, implantation, and gestation in the mouse.
The ob/ob mouse has a complete absence of circulating leptin, resulting in obesity and infertility. Using the minimum daily dose of leptin required to maintain normal body weight and sexual maturation (5 mg/kg, ip), leptin-treated ob/ob females were mated with either wild-type (+/+) or leptin-treated ob/ob males. The leptin treatment continued throughout pregnancy until weaning or was withdrawn at 0.5, 3.5, 6.5, or 14.5 d post coitum (dpc). Normal pregnancy and parturition with pups of normal weight resulted when ob/ob females were mated with +/+ males and leptin treatment was continued throughout pregnancy (6 of 8 pregnancies), to 14.5 dpc (6 of 8 pregnancies), or to 6.5 dpc (9 of 12 pregnancies). Pregnancy did not result when treatment was stopped at 3.5 dpc (1 of 7 pregnancies) or 0.5 dpc (0 of 6 pregnancies). Similar results were obtained when leptin-treated ob/ob females were mated with leptin-treated ob/ob males. The newborn pups failed to survive after birth in groups treated with leptin up to 14.5 and 6.5 dpc despite reinstating leptin at birth. This appeared to be due to a lack of development of the mammary glands. In conclusion, we have shown that leptin is essential for normal preimplantation and/or implantation processes. It is also essential for normal development of the mammary glands, but is not required for pregnancy and parturition once implantation is established.
Malik
N M
NM
Department of Physiology, St. Georges Hospital Medical School, London, United Kingdom SW17 0RE. nmalik@sghms.ac.uk
Carter
N D
ND
Murray
J F
JF
Scaramuzzi
R J
RJ
Wilson
C A
CA
Stock
M J
MJ
D000818:Animals; D010064:Embryo Implantation / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005306:Fertilization / Q000187:drug effects / Q000502:physiology*; D020738:Leptin / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000254:growth & development; D051379:Mice; D009765:Obesity / Q000235:genetics / Q000503:physiopathology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D020738:Leptin