Deficits in female reproductive function in GH-R-KO mice; role of IGF-I

Mice homozygous for targeted disruption of the GH receptor/GH binding prote in gene (GH-R-KO mice; -/-) exhibit reduced plasma IGF-I levels, elevated p lasma GH levels, and dwarf phenotype. Although most GH-R-KO mice are fertil e, age at first conception is greatly delayed in -/- x -/- matings. Here we report that the age of vaginal opening is significantly delayed in GH-R-KO vs. normal mice, but it can Se advanced by treatment with recombinant huma n (rh)IGF-I. In pregnant GH-R-KO females, fetal size is reduced and pregnan cy is prolonged while placental weight is, unexpectedly, increased. Alterat ions in fetal and placental weight are related to maternal rather than feta l genotype. Moreover, litter size and body weight of newborn pups are signi ficantly reduced in GH-R-KO vs. normal females. Reduction in litter size re flects both dam and sire effects. We conclude that GH resistance and conseq uent reduction in peripheral IGF-I levels is associated with delay of femal e puberty, alterations in fetal and placental growth, delay of parturition, and reduced litter size.