Endogenous LIF participates in the protective effect of progesterone on lypopolisaccharide-induced embryonic resorption in mice

AISEMBERG J,; VERCELLI C,; BILLI S,; CELLA M,; WOLFSON M,; FRANCHI A.

Rio de Janeiro, Brasil

Simposio; 2nd Symposium on Reproductive Immunology; 2009

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0pt; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} p.MsoBodyText, li.MsoBodyText, div.MsoBodyText {margin:0pt; margin-bottom:.0001pt; text-align:justify; line-height:200%; mso-pagination:widow-orphan; font-size:12.0pt; mso-bidi-font-size:10.0pt; font-family:Arial; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US; font-weight:bold;} @page Section1 {size:595.3pt 841.9pt; margin:70.85pt 85.05pt 70.85pt 85.05pt; mso-header-margin:35.4pt; mso-footer-margin:35.4pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Introduction. Lipopolysaccharide (LPS) administration to mice on day 7 of pregnancy produced 100% of embryonic resorption (ER) after 24 h. Progesterone (P) is critical for pregnancy as shown by its immunomodulatory effects in maternal tolerance via leukemia inhibitory factor (LIF). Several studies suggest an essential role for LIF in the host inflammatory response to endotoxemia. Our aim was to evaluate P involvement in the mechanism of LPS-induced ER and LIF contribution to P effects. Materials and methods. BALB/c females were treated with LPS (1mg/g) or vehicle for 6 h. Serum P was quantified and uteri were removed to determine LIF mRNA levels. LIF mRNA expression, prostaglandin E2 (PGE2) and nitric oxide (NO) levels were determined in uterine cultures incubated with and without LPS, P, recombinant LIF and LIF antibody. Results. We found a fall in P levels after LPS treatment and ER prevention by hormonal supplementation. LIF mRNA expression in LPS-treated mice was significantly higher than in control groups and the same effect was observed, for the first time, by P incubation. P and exogenous LIF block LPS–induced augmentation of pro-inflammatory molecules, NO and PGE2. Also, we found that endogenous LIF participates in P effects preventing NO increase. Conclusions. Our observations strongly support an hormonal contribution to successful pregnancy and its possible therapeutic apply for prevention of septic abortion.