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-tr eated ob/ob females were mated with either wild-type (+/+) or leptin-treate d ob/ob males. The leptin treatment continued throughout pregnancy until we aning or was withdrawn at 0.5, 3.5, 6.5, or 14.5 d post coitum. (dpc). Norm al pregnancy and parturition with pups of normal weight resulted when ob/ob females were mated with +/+ males and leptin treatment was continued throu ghout 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 w as 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 reinstat ing leptin at birth. This appeared to be due to a lack of development of th e 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 preg nancy and parturition once implantation is established.