Journal Article

Uterine Endoplasmic Reticulum Stress and Its Unfolded Protein Response May Regulate Caspase 3 Activation in the Pregnant Mouse Uterus

Subedi, Kalpana, Kyathanahalli, Chandrashekara, Condon, Jennifer C., Jeyasuria, Pancharatnam, Suresh, Arvind

2013

Overview

We have previously proposed that uterine caspase-3 may modulate uterine contractility in a gestationally regulated fashion. The objective of this study was to determine the mechanism by which uterine caspase-3 is activated and consequently controlled in the pregnant uterus across gestation. Utilizing the mouse uterus as our gestational model we examined the intrinsic and extrinsic apoptotic signaling pathways and the endoplasmic reticulum stress response as potential activators of uterine caspase-3 at the transcriptional and translational level. Our study revealed robust activation of the uterine myocyte endoplasmic reticulum stress response and its adaptive unfolded protein response during pregnancy coinciding respectively with increased uterine caspase-3 activity and its withdrawal to term. In contrast the intrinsic and extrinsic apoptotic signaling pathways remained inactive across gestation. We speculate that physiological stimuli experienced by the pregnant uterus likely potentiates the uterine myocyte endoplasmic reticulum stress response resulting in elevated caspase-3 activation, which is isolated to the pregnant mouse myometrium. However as term approaches, activation of an elevated adaptive unfolded protein response acts to limit the endoplasmic reticulum stress response inhibiting caspase-3 resulting in its decline towards term. We speculate that these events have the capacity to regulate gestational length in a caspase-3 dependent manner.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Activation / Animals / Apoptosis / Caspase / Caspase 3 - metabolism / Caspase-3 / Contractility / Cytochrome / Endoplasmic reticulum / Endoplasmic Reticulum Stress - physiology / Enzyme Activation - physiology / Female / Gestation / Gynecology / Mice / Muscle Cells - cytology / Muscle Cells - enzymology / Myometrium / Myometrium - cytology / Myometrium - enzymology / Obstetrics / Physiology / Pregnancy / Pregnancy - physiology / Premature labor / Protein Biosynthesis - physiology / Protein folding / Proteins / Quality control / Signal transduction / Signal Transduction - physiology / Signaling / Stress / Stresses / Studies / Transcription / Transcription, Genetic - physiology / Uterus / Womens health