Colony-stimulating factor-1 blocks early pregnancy in mice.
To elucidate the mechanisms underlying the suspected immune-related pregnancy failures in humans, we established experimental systems to induce pregnancy blocking and abortion in mice. One system, based on the preimmunization of C57BL/6J females with a syngeneic regressor tumor, is described. Such females fail to develop normal gestations when mated to C57BL/6J x DBA/2 F-1 (B6D2F-1) males or DBA/2 males but sustain normal pregnancies when impregnated by CBA/J or C57BL/6 males. An investigation into the cause of these male-specific pregnancy failures led us to identify colony-stimulating factor-1 (CSF-1) as responsible for both pregnancy-block and resorption of embryos. Indeed, injection of very small amounts of CSF-1 into plugged females, for the first 5 days of pregnancy, was sufficient to block B6D2F-1-induced gestations but had no effect on CBA/J-mated females. It also induced a high rate of fetal resorptions in the sensitive mating. These results suggest a novel mechanism underlying pregnancy failures: a mechanism based on cytokines and their effect on early embryonic development in certain mating combinations.
Tartakovsky
B
B
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Goldstein
O
O
Brosh
N
N
D000022:Abortion, Spontaneous / Q000209:etiology; D000818:Animals; D004351:Drug Resistance; D005260:Female; D005327:Fetal Resorption / Q000209:etiology; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000276:immunology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects* / Q000276:immunology; D013045:Species Specificity
D016173:Macrophage Colony-Stimulating Factor