Uterine endoplasmic reticulum stress and its unfolded protein response may regulate caspase 3 activation in the pregnant mouse uterus.
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.
Department of Obstetrics and Gynecology, Magee Women's Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America ; Department of Cell Biology, Magee Women's Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Arvind
A
Suresh
Kalpana
K
Subedi
Chandrashekara
C
Kyathanahalli
Pancharatnam
P
Jeyasuria
Jennifer C
JC
Condon
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D051379:Mice; D032342:Muscle Cells / Q000166:cytology / Q000201:enzymology*; D009215:Myometrium / Q000166:cytology / Q000201:enzymology*; D011247:Pregnancy / Q000502:physiology*; D014176:Protein Biosynthesis / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology
C505409:Casp3 protein, mouse; D053148:Caspase 3