Preimplantation apoptotic endometrial caspase-3-mediated phospholipase A2 activation: a potential component in programming uterine receptivity.

OBJECTIVE: To examine the activation and consequence of uterine apoptotic caspase-3 action on 1 day after coitus (dpc) in the pregnant mouse. We have previously demonstrated that in a pregnant uterus, caspase-3 activation from mid to late gestation isolated to the myometrial compartment is largely nonapoptotic and controls uterine quiescence. Additionally, we had demonstrated that apoptotic caspase-3 activation isolated to the endometrial compartment at term regulated endometrial prostaglandin synthesis. DESIGN: Uteri were isolated from pseudopregnant and nonligated controls and unilateral and bilateral ligated uterine horn mouse models at 1, 3, and 6 dpc. Uteri were examined for apoptotic indices, such as caspase-3 activation and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling staining. Immunohistochemical analysis identified the site of uterine apoptotic caspase-3 activation. The truncated form of phospholipase A2 was examined as a measure of apoptotic caspase-3-mediated calcium independent phospholipase A2 (iPLA2) activation. RESULT(S): We identified the site and impact of uterine apoptotic caspase-3 activation using uteri isolated from nonpregnant control animals at estrous and diestrous and control pregnant mice at 1-19 dpc. Our analysis revealed that apoptotic caspase-3 and iPLA2 activation were limited to the endometrial compartments of the control and unilateral ligated uteri on 1 dpc and were not found in the pseudopregnant or bilateral ligated uterine horn or on 3 or 6 dpc in the control and unilateral ligated uteri. CONCLUSION(S): In this study, we determined that uterine caspase-3 activation on 1 dpc, which is endometrial and apoptotic in nature, may play a potential role in regulating the previously reported preimplantation surge in endometrial PGE2 synthesis through apoptotic caspase-3-mediated iPLA2 activation. Our data indicate that the presence of a conceptus on 1 dpc likely triggers an increase in endometrial apoptotic caspase-3-mediated iPLA2 activation. When activated, iPLA2 causes the hydrolysis of fatty acids, resulting in arachidonic acid release and PGE2 production, which has been demonstrated to act in a leutoprotective manner in early pregnancy, prolonging progesterone synthesis and promoting uterine receptivity.

Serum macrophage migration inhibitory factor in the prediction of preterm delivery.

OBJECTIVE: Macrophage migration inhibitory factor is a soluble mediator that helps govern the interaction between cytokines and stress hormones (eg, cortisol). We determined whether maternal macrophage migration inhibitory factor levels predicted subsequent preterm delivery. STUDY DESIGN: A nested case-control study measuring serum macrophage migration inhibitory factor concentration at 9-23 weeks' gestation in women who ultimately delivered preterm (n = 60) compared with control women who delivered at term (n = 122). We also examined the connection of macrophage migration inhibitory factor with self-reported psychosocial variables. RESULTS: Macrophage migration inhibitory factor was elevated in the preterm delivery cases (P = .0004), and log macrophage migration inhibitory factor concentration showed a graded response relationship with likelihood of preterm delivery. High-macrophage migration inhibitory factor was also associated with maternal risk-taking behavior, which itself was a risk factor for preterm delivery. Macrophage migration inhibitory factor remained associated independently with preterm delivery after adjusting regression models for several other preterm delivery risk factors (odds ratio, 3.11, 95% confidence interval, 1.54-6.30). CONCLUSION: High-serum macrophage migration inhibitory concentration in early to midpregnancy is linked with subsequent preterm delivery.