Related Experiment Video
Updated: May 10, 2026
A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
N,N-dimethylacetamide regulates the proinflammatory response associated with endotoxin and prevents preterm birth
Sruthi Sundaram1, Charles R Ashby, Ryan Pekson
1Department of Pharmaceutical Sciences, St. John's University, Queens, New York 11439, USA.
Insights
N,N-dimethylacetamide (DMA) prevents preterm birth in mice by reducing inflammation. This non-toxic compound offers a potential new therapy for inflammatory disorders and premature delivery.
Area of Science:
- Reproductive biology
- Immunology
- Pharmacology
Background:
- Preterm birth is a major cause of infant mortality, often linked to intrauterine infections and inflammation.
- Proinflammatory cytokines play a key role in the development of preterm birth.
- Current treatments for inflammation-associated preterm birth are limited.
Purpose of the Study:
- To investigate the potential of N,N-dimethylacetamide (DMA) as a therapeutic agent to prevent preterm birth.
- To elucidate the anti-inflammatory mechanisms of DMA in the context of pregnancy.
Main Methods:
- Timed pregnant C57BL/6 mice were administered endotoxin to induce preterm birth.
- DMA was administered at varying doses to assess its protective effects.
- Histologic analysis of placental tissue was performed to evaluate inflammatory cell infiltration.
- Immunoblotting was used to analyze the expression of key cytokines (IL-1β, TNF-α, IL-6, IL-10).
- In vitro studies examined DMA's effect on macrophage function and nuclear factor-kB (NF-kB) translocation.
Main Results:
- DMA significantly prevented endotoxin-induced preterm birth and rescued pups from spontaneous abortion in a dose-dependent manner.
- Histologic examination showed DMA suppressed inflammatory cell infiltration in placental tissue.
- DMA modulated the expression of proinflammatory cytokines (IL-1β, TNF-α, IL-6) and increased IL-10 expression.
- In vitro, DMA suppressed macrophage function and inhibited NF-kB nuclear translocation.
Conclusions:
- N,N-dimethylacetamide (DMA) demonstrates significant efficacy in preventing preterm birth in a murine model.
- DMA exerts its protective effects by suppressing the maternal proinflammatory response and regulating cytokine expression.
- DMA represents a promising, non-toxic therapeutic candidate for preterm birth and other inflammatory conditions.
Abstract:
The proinflammatory response leads to various types of pathologic pathways, including the development of preterm birth. Preterm birth occurs in 12% of deliveries in the United States and causes more than 70% of perinatal morbidity and mortality. The most common cause of spontaneous preterm birth is intrauterine infection in the mother. There is accumulating evidence indicating that the release of proinflammatory cytokines plays a critical role in the pathogenesis of inflammation-associated premature delivery. We found that the common organic solvent, N,N-dimethylacetamide (DMA), prevents endotoxin-induced preterm birth in timed pregnant C57BL/6 embryonic day (E)15.5 mice and rescues their pups from spontaneous abortion at doses many-fold lower than those currently used clinically and in a dose-dependent fashion. We also provide histologic evidence that DMA suppresses the endotoxin-triggered proinflammatory response by significantly attenuating inflammatory cell infiltration of placental tissue. Furthermore, immunoblotting analysis of placental tissue harvested from our murine models revealed DMA-mediated regulation of expression of the proinflammatory cytokines IL-1β, tumor necrosis factor α, and IL-6, and increased expression of the regulatory inflammatory cytokine IL-10. By using in vitro studies, we provide evidence that DMA suppresses macrophage function and that this small molecule prevents nuclear translocation of nuclear factor-kB. These results suggest that DMA represents a newly discovered, nontoxic therapy for a broad range of inflammatory disorders.
