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Colony-stimulating factor-1 blocks early pregnancy in mice
B Tartakovsky1, O Goldstein, N Brosh
1Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Abstract:
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.
Insights
Immune-related pregnancy failures in mice were studied. Colony-stimulating factor-1 (CSF-1) was identified as a key factor causing pregnancy block and embryo resorption in specific mating combinations.
Area of Science:
- Reproductive Immunology
- Developmental Biology
- Immunology
Background:
- Immune-related pregnancy failures are a concern in humans.
- Experimental models are needed to understand these failures.
- Specific mating combinations can lead to pregnancy complications.
Purpose of the Study:
- To elucidate mechanisms of immune-related pregnancy failures.
- To establish a mouse model for studying pregnancy block and abortion.
- To identify factors responsible for male-specific pregnancy failures.
Main Methods:
- Pre-immunization of female mice with syngeneic regressor tumor.
- Mating females with different male strains (B6D2F-1, DBA/2, CBA/J, C57BL/6).
- Injection of colony-stimulating factor-1 (CSF-1) during early pregnancy.
Main Results:
- Pre-immunized females showed male-specific pregnancy failures.
- Colony-stimulating factor-1 (CSF-1) was identified as responsible for pregnancy block and embryo resorption.
- Low-dose CSF-1 injection blocked gestation in sensitive matings and caused fetal resorptions.
Conclusions:
- A novel mechanism for pregnancy failure involving cytokines and early embryonic development is suggested.
- CSF-1 plays a critical role in specific mating-induced pregnancy failures.
- Cytokine-mediated effects on early embryonic development can lead to pregnancy loss.