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

Abstract

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.