CONICET | Buscador de Institutos y Recursos Humanos

LPS administration to early pregnant mice produced embryonic resorption (ER) after 24h and resulted in enhanced signs of sepsis increasing pro-inflammatory molecules production at implantation sites. The non-rejection of the fetus in normal pregnancies has been attributed in part to the presence of immunomodulatory molecules within the feto-placental unit. One such protein is PP14 also known as progestagen-dependent endometrial protein which is synthesized by the human endometrium and decidua. LIF, another one is a secreted cytokine with pleiotropic functions which include maternal tolerance. The aim of this work was to characterize Gd and LIF production in mice and the possible modulation of LIF and pro-inflammatory mediators by progesterone (P). Balb/c females were injected with LPS (1mg/g) at day 7 of pregnancy. After 6h tissues were removed to determine Gd protein, LIF mRNA levels (RT-PCR) and sera for P determination (RIA). Prostaglandin E (PGE), nitric oxide (NO) and TNFa were determined in 48h cultures. Mice treated with LPS showed lower levels of serum P compared to control (p<0.01). LIF mRNA expression in these mice were significantly higher (p<0.01) than in control. P co-incubation increased its mRNA expression in normal pregnant mice (p<0.01) suggesting that P up-regulated LIF but P was able to block LPS-induced LIF expression (p<0.001). We also found that PGE, NO and TNFa synthesis augmented by LPS and this effect was abrogated by P. Gd protein levels in LPS-treated mice was significantly lower (p<0.01) than in control group both in uterus (p<0.001) and decidua (p<0.01). We demonstrate for the first time Gd production by murine uterus and decidua and LIF modulation by P in mice. These results suggest that low levels of P during inflammmation may contribute to the inflammatory disorder that concludes in ER. PICT2004/n°20207.