title: Role of colony-stimulating factor-1 in reproduction and development.
abstract: The CSF-1 null mouse, osteopetrotic, has provided a powerful model in which to study the biological functions of CSF-1. In this review, I will describe our studies that have used this mouse model to determine the impact of a lack of CSF-1 on developmental processes and in reproduction. A role for CSF-1 in reproduction was originally suggested by the sex steroid hormone-regulated uterine epithelial synthesis of CSF-1 and the expression of its receptor in trophoblast and decidual cells. Studies on the fertility of CSF-1 deficient osteopetrotic mice (csfmop/csfmop) mice confirmed this suggestion and in addition revealed an unexpected function for CSF-1 in male fertility. In both sexes, CSF-1 appears to regulate gonadal steroidogenesis, probably through its action on macrophages that are abundant throughout the ovary and testis. In the female, CSF-1 affects ovulation in vivo and in vitro, and impacts the preimplantation embryo, increasing both its rate of development and the number of trophectodermal cells in the blastocyst. CSF-1 also has a role in mammary gland development during pregnancy, since at mid-gestation in csfmop/csfmop mice, ductal branching is impaired, and after partiturition, there is a failure to switch to lactation. The relative failure of csfmop/csfmop mice to respond to external stimuli also suggested a role for CSF-1 in the brain. CSF-1 mRNA is expressed in a regional specific manner in the brain through development whilst the CSF-1 receptor is expressed throughout the brain in microglia. CSF-1 is neurotrophic in embryonic neuronal cultures and its absence in csfmop/csfmop mice results in severe electro-physiological abnormalities in the cortex. This suggests that CSF-1 is a neurotrophic factor acting through the microglia. The pleiotropic roles for CSF-1 in reproduction and in the brain suggest that CSF-1 exerts many of its action through the trophic activities of cells of the mononuclear phagocytic lineage.
authors.affiliation: Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, New York 10461, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Pollard
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000473:pathology; D001940:Breast / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis; D007774:Lactation / Q000502:physiology; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism; D010022:Osteopetrosis / Q000196:embryology / Q000235:genetics; D010053:Ovary / Q000378:metabolism; D010641:Phenotype; D011247:Pregnancy; D051381:Rats; D012098:Reproduction / Q000502:physiology*; D012678:Sensation Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013737:Testis / Q000378:metabolism
chemical_list: D012739:Gonadal Steroid Hormones; D016173:Macrophage Colony-Stimulating Factor