Absence of Colony Stimulating Factor-1 in Osteopetrotic (csfmop/csfmop) Mice Disrupts Estrous Cycles and Ovulation1

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.