Angiopoietin-2 primes infection-induced preterm delivery.

Current knowledge on the participation of angiopoietin-2 (Ang-2) in the inflammatory process and on the importance of bacterial endotoxins (LPS) in the induction of preterm delivery (PTD) led us to investigate the role of Ang-2/LPS interplay in the pathogenesis of PTD. At a first stage, Ang-2 was measured at the end of the first trimester of pregnancy in the serum of 50 women who delivered prematurely; of 88 women well-matched for age and parity who delivered full-term; and of 20 non-pregnant healthy women. Ang-2 was greater in pregnant than in non-pregnant women. The time until delivery was shorter among those with Ang-2 greater than 4 ng/ml (odds ratio for delivery until week 34; p: 0.040). To further investigate the role of Ang-2 for PTD, an experimental model of PTD induced by the intraperitoneal injection of LPS in mice was used. Ang-2 was administered intraperitoneally before LPS on day 14 of pregnancy. When Ang-2 was administered before the LPS diluent, all mice delivered full-term. However, administration of Ang-2 prior LPS accelerated further the time until delivery. Sacrifice experiments showed that the effect of Ang-2 was accompanied by decrease of the penetration of Evans Blue in the embryos and by increase of its penetration in maternal tissues. In parallel, the concentration of tumour necrosis factor-alpha in the maternal circulation, in fetal tissues and in the placentas was significantly decreased. Results indicate that Ang-2 accelerated the phenomena of PTD induced by LPS. This is related with deprivation of fetal perfusion.

Alterations in the cellular component of the maternal immune system in a murine preterm delivery model.

OBJECTIVE: Investigate changes in the cellular component of maternal immune system in a murine preterm delivery (PTD) model. METHODS: C57BL/6 J mice were mated and on day 14.5 after plugging either whole blood was harvested or Escherichia coli lipopolysaccharide (LPS) was intraperitoneally injected. PTD resulted within 24 h. Ten to twelve hours after LPS injection (initiation of labor), whole blood was harvested. Annexin-V, CD3, CD4, CD8, CD80 and CD86 were counted after running through flow cytometer with gating for mononuclear cells. Control group consisted of non-pregnant mice. RESULTS: Rate of apoptosis of monocytes and lymphocytes and expression of CD80(+) and CD86(+) was increased in non-pregnant mice after LPS injection (p = 0.009, p = 0.002, p < 0.001 and p = 0.005, respectively), but remained unaltered in pregnant mice. Expression of CD3(+)/4(+) and CD3(+)/8(+) on lymphocytes was increased after LPS injection in both pregnant (p = 0.001, p = 0.011, respectively) and non-pregnant mice (p = 0.008, p < 0.001, respectively). CONCLUSIONS: Cellular component of maternal non-specific immune system is remain suppressed in pregnant mice, whereas specific immune responses of pregnant mice to infection are similar to these of non-pregnant mice.