Maternal immunity and pregnancy outcome: focus on preconception and autophagy.

Modulation of the maternal immune system before conception has a major role in determining subsequent pregnancy outcome. However, this has been a neglected area of investigation. There is a correlation between the length of time a woman is exposed to semen from her male partner and the development of regulatory T cells that limit a maternal antifetal immune response. Similarly, the composition of the vaginal microbiota influences the capacity of microorganisms to bypass the cervical barrier and colonize the uterus before pregnancy. The extent that this preconception colonization influences pre- and post-implantation gestational events depends on the types of microbes present, the genetic make-up of the mother and environmental influences on the magnitude and direction of her immune responses. Prepregnancy uterine and placental colonization with commensal bacteria may be beneficial to the fetus and newborn by generating tolerance to organisms that enhance postnatal well-being. Efforts to prevent or stop the progression of premature myometrial contractions have been limited because of an incomplete understanding of the mechanism(s) that trigger this occurrence. Based on recent studies of autophagy during gestation and parturition, inhibition of autophagy in myometrial cells may be the critical factor leading to a sequence of events culminating in induction of myometrial contractions either prematurely or at term.

Altered autophagy induction by sera from pregnant women with pre-eclampsia: a case-control study.

OBJECTIVE: Mechanisms leading to pre-eclampsia remain incompletely defined. Autophagy is a conserved process necessary for cell survival under adverse conditions. We hypothesised that sera from women with healthy pregnancies and women with pre-eclampsia differed in autophagy induction. DESIGN: A case-control study. SETTING: Weill Cornell Medical College. POPULATION: Twenty-four normotensive pregnant women and 20 women with pre-eclampsia. METHODS: Sera were incubated with peripheral blood mononuclear cells (PBMCs) from female donors. After 48 hours the PBMCs were lysed and the intracellular concentration of p62 was determined by enzyme-linked immunosorbent assay (ELISA). Its concentration is inversely proportional to the extent of autophagy induction. Serum endoglin, interleukin 13 (IL-13), insulin-like growth factor 1 (IGF-1), and transforming growth factor ß1 (TGF-ß1) levels were quantitated by ELISA. MAIN OUTCOME MEASURES: Differences in autophagy induction and serum mediator levels in the two groups. RESULTS: Autophagy induction increased with gestational age in sera from normotensive women (P = 0.0045), but not in women with pre-eclampsia. In the presence of an autophagy inducer, the capacity for autophagy induction decreased with gestational age in sera from women with pre-eclampsia (P = 0.0235), but not from controls. Endoglin concentrations were positively associated with the extent of autophagy induction in controls only (P = 0.0141). There was no association between autophagy and serum IL-13, IGF-1, or TGF-ß1 levels. CONCLUSIONS: Sera from women with pre-eclampsia differ from normotensive women by their inability to induce autophagy as a function of gestational age.

Oxidative stress in pathological pregnancies.

Oxidative stress (OS) plays a role in pregnancy at risk of pre-eclampsia, diabetes and premature labour. We measured three markers of OS: total antioxidant capacity (TAC), thiolyte capacity and pro-oxidant capacity in 45 women: 15 normal pregnancies, 17 pathological pregnancies (pre-eclampsia and pregestational diabetes) and 13 delivered pre-term. Plasma TAC (µmol/ml) values in patients with pathological pregnancies (235.67 ± 70.08) (p(1) = 0.0086) and pre-term labour (243.51 ± 50.52) (p(2) = 0.0479) were significantly reduced as compared with the controls (306.78 ± 70.08). Thiolyte capacity (µmol/ml) in the pathological pregnancies (326.03 ± 78.24) (p(3) = 0.0029) and in pre-term labour (335.94 ± 76.63) (p(4) = 0.0084) groups were significantly reduced compared with the control group (417.48 ± 39.76) (p < 0.05). Pro-oxidant capacity (mg/100 ml) in the pathological pregnancies (94.11 ± 26.13) (p(5) = 0.00034) and in pre-term labour (87.18 ± 20.28) (p(6) = 0.00044) groups were significantly higher compared with the controls (60.27 ± 6.33). Elevated OS values were seen in pathological pregnancies. This supports the important role of OS in diseases in pregnancy, particularly pre-eclampsia, diabetes and pre-term birth.