Absence of colony stimulating factor-1 in osteopetrotic (csfmop/csfmop) mice disrupts estrous cycles and ovulation.
Colony stimulating factor-1 (CSF-1) is a hematopoietic growth factor required for the recruitment, proliferation, and differentiation of mononuclear phagocytes. In addition, CSF-1 is expressed in the female reproductive tract coincident with CSF-1 receptor localization on preovulatory oocytes, ovarian and uterine macrophages, decidual cells, and trophoblast. A role for CSF-1 in female reproduction was confirmed by studies on CSF-1-deficient, osteopetrotic (csfmop/csfmop) mice, which suffer from low pregnancy rates and smaller litter sizes compared to wild-type mice. The present study was designed to determine the exact causes of the preimplantation fertility defects in these mutant mice. Female csfmop/csfmop mice have extended estrous cycles compared to wild-type females, and s.c. administration of CSF-1 from birth restores estrous cyclicity. These mice fail to display the characteristic proestrous surge in circulating estradiol-17beta. However, concentrations of this hormone are normal during the remainder of the cycle. Furthermore, csfmop/csfmop females have significantly lower ovulation rates than wild-type mice, but the implantation rates of fertilized oocytes are normal. Serum pregnancy concentrations of progesterone are also normal in csfmop/csfmop females, in line with the relatively normal progression of pregnancy in these mice. Thus, the major effect of CSF-1 on female reproductive function is on the frequency and rate of ovulation, indicating a major role for this growth factor in regulating follicular development and ovulation.
Cohen
P E
PE
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Zhu
L
L
Pollard
J W
JW
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D047108:Embryonic Development; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D004971:Estrus / Q000502:physiology*; D005260:Female; D005838:Genotype; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D010053:Ovary / Q000166:cytology; D010060:Ovulation / Q000502:physiology*; D011247:Pregnancy; D011374:Progesterone / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D014599:Uterus / Q000166:cytology / Q000187:drug effects; D014621:Vagina / Q000166:cytology / Q000187:drug effects
D011374:Progesterone; D004958:Estradiol; D016173:Macrophage Colony-Stimulating Factor