The Cell-Surface Isoform of Colony Stimulating Factor 1 (CSF1) Restores but Does Not Completely Normalize Fecundity in CSF1-Deficient Mice

• Published in: Biology of reproduction Vol. 74; no. 2; pp. 331 - 336
• Main Authors: OVADIA, Shira, INSOGNA, Karl, YAO, Gang-Qing
• Format: Journal Article
• Language: English
• Published: Madison, WI Society for the Study of Reproduction 01-02-2006
• Subjects: Animals; Biological and medical sciences; Cell Membrane - metabolism; Female; Fertility - genetics; Fundamental and applied biological sciences. Psychology; Lung - metabolism; Macrophage Colony-Stimulating Factor - genetics; Macrophage Colony-Stimulating Factor - metabolism; Male; Mammalian reproduction. General aspects; Mice; Mice, Transgenic; Osteoporosis - genetics; Pregnancy; Protein Isoforms - genetics; Protein Isoforms - metabolism; Spermatozoa - physiology; Uterus - metabolism; Vertebrates: reproduction; Spermatozoa; sperm motility and transport; growth factors; Rodentia; Transgenic animal; Germinal cell; Colony stimulating factor; Pregnancy; Vertebrata; Mammalia; Mouse; Uterus; gene regulation; Female genital system
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.105.045047

The complete genetic absence of colony stimulating factor 1 (CSF1) in CSF1-deficient Csf1 op /Csf1 op mice leads to reproductive defects in males and females. Although the cell-surface or membrane-bound isoform of CSF1 (mCSF1)
is biologically active in bone, little is known about its role in reproduction. Transgenic mice expressing mCSF1 under the
control of the 2.4-kb rat collagen type I alpha promoter were developed [ Tg(Col1a1-mCSF1)1Gqy ] and bred onto a Csf1 op /Csf1 op background [ Csf1 op /Csf1 op ; Tg(Col1a1-mCSF1)1Gqy ] to examine the effects of the mCSF1 isoform in bone in vivo. Surprisingly, when interbred, these mice were fertile. The
Csf1 op /Csf1 op ; Tg(Col1a1-mCSF1)1Gqy transgenic male mice have normal libido, sperm number and percent of motile sperm. In Csf1 op /Csf1 op ; Tg(Col1a1-mCSF1)1Gqy females, puberty and estrus cycles are at expected age and duration. Further, females are able to carry pregnancies to term
and nurse their offspring. Crosses of Csf1 op /Csf1 op ; Tg(Col1a1-mCSF1)1Gqy males or females with their control littermates showed no significant differences in either number or viability of offspring.
However, crossing Csf1 op /Csf1 op ; Tg(Col1a1-mCSF1)1Gqy males with Csf1 op ; Tg(Col1a1-mCSF1)1Gqy females resulted in a decline in both the number and viability of offspring, suggesting that a subtle reproductive defect
might persist in the transgenic animals that was only manifest when the animals were interbred. Although the gravid murine
uterus expresses extremely high levels of CSF1 that are thought to be important for reproduction, uterine tissue levels of
CSF1 remained low and unchanged during pregnancy in Csf1 op /Csf1 op ; Tg(Col1a1-mCSF1)1Gqy mice. Low levels of CSF1 protein were detected in serum and in lung and uterine tissue in Csf1 op /Csf1 op ; Tg(Col1a1-mCSF1)1Gqy mouse, which likely result from the known proteolytic shedding of mCSF1 from the cell surface. These data are consistent
with the conclusion that mCSF1, when shed from the cell surface, can support reproduction and that high uterine tissue levels
of CSF1 may not be required for mouse reproduction.
Abstract
The cell-surface CSF1 isoform rescues the reproductive defects in CSF1 deficient CSF1 op /CSF1 op mice without altering uterine CSF1 tissue levels during pregnancy.