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

Abstract

To examine the activation and consequence of uterine apoptotic caspase-3 action on day 1 post coitus (dpc) in the pregnant mouse. Previously we have demonstrated that pregnant uterine caspase-3 activation from mid to late gestation isolated to the myometrial compartment is largely non-apoptotic and controls uterine quiescence. We have also previously demonstrated that apoptotic caspase-3 activation, isolated to the endometrial compartment at term regulated endometrial prostaglandin synthesis METHODS: Uteri were isolated from pseudo pregnant (PsP) and non-ligated controls (GD), unilateral (UL) and bilateral ligated (BL) uterine horn mouse models at 1, 3 and 6 dpc. Uteri were examined for apoptotic indices, such as caspase-3 activation and TUNEL staining. Immunohistochemical analysis identified the site of uterine apoptotic caspase-3 activation. The truncated form of phospholipase A2 (tiPLA2) was examined as a measure of apoptotic caspase-3 mediated iPLA2 activation. We have identified the site and impact of uterine apoptotic caspase-3 activation utilizing uteri isolated from non-pregnant control animals at estrous and diestrous and control pregnant mice at 1-19 dpc. Our analysis determined that apoptotic caspase-3 and iPLA2 activation were limited to the endometrial compartments of the control and unilateral ligated uteri on 1dpc and were not found in the pseudo pregnant or bilateral ligated uterine horn or on 3 or 6 dpc in the control and unilateral ligated uteri. 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 pre-implantation surge in endometrial PGE2 synthesis through apoptotic caspase-3 mediated iPLA2 activation. Our data indicates that the presence of a conceptus on 1 dpc likely triggers an increase in endometrial apoptotic caspase-3 mediated iPLA2 activation. iPLA2 when activated causes the hydrolysis of fatty acids resulting in arachidonic acid release and production of PGE2, which in early pregnancy has been demonstrated to act in a leutoprotective manner, prolonging progesterone synthesis and promoting uterine receptivity.