title: Leptin requirement for conception, implantation, and gestation in the mouse.
abstract: 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 The leptin treatment continued throughout pregnancy until weaning or was withdrawn at 0.5, 3.5, 6.5, or 14.5 d post coitum (dpc).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.
authors.affiliation: Department of Physiology, St. Georges Hospital Medical School, London, United Kingdom SW17 0RE. nmalik@sghms.ac.uk
authors.forename: N M
authors.initials: NM
authors.lastname: Malik
authors.forename: N D
authors.initials: ND
authors.lastname: Carter
authors.forename: J F
authors.initials: JF
authors.lastname: Murray
authors.forename: R J
authors.initials: RJ
authors.lastname: Scaramuzzi
authors.forename: C A
authors.initials: CA
authors.lastname: Wilson
authors.forename: M J
authors.initials: MJ
authors.lastname: Stock
mesh_terms: 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
chemical_list: D020738:Leptin