Specific deletion of AMP-activated protein kinase (α1AMPK) in murine oocytes alters junctional protein expression and mitochondrial physiology

PloS One
Michael J BertoldoPascal Froment

Abstract

Oogenesis and folliculogenesis are dynamic processes that are regulated by endocrine, paracrine and autocrine signals. These signals are exchanged between the oocyte and the somatic cells of the follicle. Here we analyzed the role of AMP-activated protein kinase (AMPK), an important regulator of cellular energy homeostasis, by using transgenic mice deficient in α1AMPK specifically in the oocyte. We found a decrease of 27% in litter size was observed in ZP3-α1AMPK-/- (ZP3-KO) female mice. Following in vitro fertilization, where conditions are stressful for the oocyte and embryo, ZP3-KO oocytes were 68% less likely to pass the 2-cell stage. In vivo and in cumulus-oocyte complexes, several proteins involved in junctional communication, such as connexin37 and N-cadherin were down-regulated in the absence of α1AMPK. While the two signalling pathways (PKA and MAPK) involved in the junctional communication between the cumulus/granulosa cells and the oocyte were stimulated in control oocytes, ZP3-KO oocytes exhibited only low phosphorylation of MAPK or CREB proteins. In addition, MII oocytes deficient in α1AMPK had a 3-fold lower ATP concentration, an increase in abnormal mitochondria, and a decrease in cytochrome C and PGC1α levels, s...Continue Reading

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Citations

Feb 17, 2019·Journal of Cellular Physiology·Reza MohammadinejadMilad Ashrafizadeh
Jun 9, 2018·Journal of Assisted Reproduction and Genetics·Elizabeth E PuscheckDaniel A Rappolee
Dec 14, 2018·Frontiers in Endocrinology·Melanie FaurePascal Froment
Jan 2, 2021·Frontiers in Cell and Developmental Biology·Luyao ZhangYunpeng Hou

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Methods Mentioned

BETA
transgenic
electrophoresis
PCRs
PCR
Assay
transmission electron microscopy
confocal microscopy
acetylation
histone acetylation

Software Mentioned

Light Cycler integrated
ZEN
ImageJ

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