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Leptin Requirement for Conception, Implantation, and Gestation in the Mouse

Departments of Physiology (N.M.M., J.F.M., C.A.W., M.J.S.) and Medical Genetics (N.D.C.), St. Georges Hospital Medical School, London, United Kingdom SW17 0RE; and Department of Veterinary Basic Sciences, Royal Veterinary College (R.J.S.), London, United Kingdom NW1 0TU

Address all correspondence and requests for reprints to: Dr. Nasser Malik, Department of Physiology, St. Georges Hospital Medical School, Cranmer Terrace, London, United Kingdom SW17 ORE. E-mail: nmalik{at}sghms.ac.uk

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 The leptin treatment continued throughout pregnancy until weaning or was withdrawn at 0.5, 3.5, 6.5, or 14.5 d post coitum (dpc).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.

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