A pregnancy defect in the osteopetrotic (op/op) mouse demonstrates the requirement for CSF-1 in female fertility.
Correlative evidence suggests that maternal production of the mononuclear phagocyte growth factor colony stimulating factor-1 (CSF-1) regulates placental development. In order to study the role of CSF-1 in pregnancy the fertility of CSF-1-less osteopetrotic (op/op) mutant mice was investigated. Homozygous mutant crosses (op/op x op/op) were consistently infertile. As expected, op/op males were almost completely fertile when crossed with heterozygous females. Surprisingly, op/op females when mated to heterozygote males were fertile, although at a rate that was 46% of the rate for +/op females x op/op males. These data suggest that CSF-1 is required for pregnancy. However, a maternal CSF-1 source is not absolutely necessary in that pregnancies involving +/op fathers were partially rescued, suggesting that +/op fetuses and/or +/op seminal fluid provides CSF-1 or CSF-1-induced factors which compensate for the absence of maternally produced CSF-1. Despite the complete absence of CSF-1 in the uterus and placenta of op/op mice placental weights were normal, suggesting that proliferation of decidual cells and trophoblasts, both of which express the CSF-1 receptor, may not be solely regulated by CSF-1. Histochemical staining for F4/80 antigen was used to identify macrophages in the uterus and placenta. Uterine macrophages could not be detected in virgin op/op mice although they were abundant in +/op uteri. Interestingly, macrophages could be detected in op/op uteri as uncharacteristically rounded cells in early gestation, however, they were not maintained and no macrophages were apparent beyond Day 14 of pregnancy in op/op mice. Further studies in the osteopetrotic mouse will be useful in delineating those functions required for pregnancy that are regulated by CSF-1.
Pollard
J W
JW
Department of Developmental Biology and Cancer, Albert Einstein College of Medicine (AECOM), Bronx, New York 10461.
Hunt
J S
JS
Wiktor-Jedrzejczak
W
W
Stanley
E R
ER
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002452:Cell Count; D002460:Cell Line; D004247:DNA; D005260:Female; D005298:Fertility / Q000502:physiology*; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology*; D008264:Macrophages; D051379:Mice; D008969:Molecular Sequence Data; D010022:Osteopetrosis / Q000235:genetics / Q000503:physiopathology*; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D014599:Uterus / Q000166:cytology
D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor; D004247:DNA; D016186:Receptor, Macrophage Colony-Stimulating Factor