PROBLEM: Previous data have shown that 'danger' signals, such as bacterial lipopolysaccharide (LPS) acting via toll-like receptors (TLR), are conditions antecedent to early pregnancy failure in several murine abortion models. Indeed, the abortion rate increased in the CBA x DBA/2 model after injection of tumor necrosis factor-alpha (TNF-alpha) + interferon (IFN-gamma) on gestation day (GD) 7.5 only if the LPS-TLR signaling pathway was intact. High rates of cytokine-boosted abortion >80% loss can be demonstrable in certain animal colonies that have a high endogenous (spontaneous) rate of resorption (30-50%). A specific role for LPS on GD 0.5 determines the endogenous loss rate and on GD 6.5 the responsiveness to cytokine boosting of losses. Th1 cytokines (or the stress that induces these cytokines) increase intestinal permeability and absorption of luminal contents. It was predicted that intestinal availability of LPS was a major factor in the endogenous and cytokine-boosted resorption rates. METHOD OF STUDY: A fixed weight of fresh mouse droppings from CBA/J female mice house in a high-abortion-rate (30-40%) colony at Clamart, France was homogenized and filtered. Fresh mouse droppings from a low-abortion-rate (10-15%) colony in Berlin, Germany were similarly processed. LPS was assayed using the Limulus amoebocyte lysate bioassay. RESULTS: To our surprise, there was no significant difference in LPS content of fecal samples from the two colonies. CONCLUSION: A high endogenous rate of abortion and cytokine (or stress) boosted abortion in the CBA x DBA/2 model is not explained by the LPS content of feces. Possible explanations include: fecal LPS does not reflect small intestinal LPS, there are additional TLR signals besides LPS that are important and endogenous stress levels may be higher in high-abortion-rate colonies, so permeability of the intestine (and Th1 cytokine levels) may be already higher. These data have implications for studies on the role of flora in human pregnancy problems.
PROBLEM: Previous data have shown that 'danger' signals, such as bacterial lipopolysaccharide (LPS) acting via toll-like receptors (TLR), are conditions antecedent to early pregnancy failure in several murine abortion models. Indeed, the abortion rate increased in the CBA x DBA/2 model after injection of tumor necrosis factor-alpha (TNF-alpha) + interferon (IFN-gamma) on gestation day (GD) 7.5 only if the LPS-TLR signaling pathway was intact. High rates of cytokine-boosted abortion >80% loss can be demonstrable in certain animal colonies that have a high endogenous (spontaneous) rate of resorption (30-50%). A specific role for LPS on GD 0.5 determines the endogenous loss rate and on GD 6.5 the responsiveness to cytokine boosting of losses. Th1 cytokines (or the stress that induces these cytokines) increase intestinal permeability and absorption of luminal contents. It was predicted that intestinal availability of LPS was a major factor in the endogenous and cytokine-boosted resorption rates. METHOD OF STUDY: A fixed weight of fresh mouse droppings from CBA/J female mice house in a high-abortion-rate (30-40%) colony at Clamart, France was homogenized and filtered. Fresh mouse droppings from a low-abortion-rate (10-15%) colony in Berlin, Germany were similarly processed. LPS was assayed using the Limulus amoebocyte lysate bioassay. RESULTS: To our surprise, there was no significant difference in LPS content of fecal samples from the two colonies. CONCLUSION: A high endogenous rate of abortion and cytokine (or stress) boosted abortion in the CBA x DBA/2 model is not explained by the LPS content of feces. Possible explanations include: fecal LPS does not reflect small intestinal LPS, there are additional TLR signals besides LPS that are important and endogenous stress levels may be higher in high-abortion-rate colonies, so permeability of the intestine (and Th1 cytokine levels) may be already higher. These data have implications for studies on the role of flora in human pregnancy problems.
Authors: Astrid Friebe; Alison J Douglas; Emilia Solano; Sandra M Blois; Evelin Hagen; Burghard F Klapp; David A Clark; Petra C Arck Journal: J Mol Med (Berl) Date: 2011-03-10 Impact factor: 4.599