| First Author | Bertoldo MJ | Year | 2015 |
| Journal | PLoS One | Volume | 10 |
| Issue | 3 | Pages | e0119680 |
| PubMed ID | 25767884 | Mgi Jnum | J:232919 |
| Mgi Id | MGI:5780413 | Doi | 10.1371/journal.pone.0119680 |
| Citation | Bertoldo MJ, et al. (2015) Specific deletion of AMP-activated protein kinase (alpha1AMPK) in murine oocytes alters junctional protein expression and mitochondrial physiology. PLoS One 10(3):e0119680 |
| abstractText | 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 alpha1AMPK specifically in the oocyte. We found a decrease of 27% in litter size was observed in ZP3-alpha1AMPK-/- (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 alpha1AMPK. 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 alpha1AMPK had a 3-fold lower ATP concentration, an increase in abnormal mitochondria, and a decrease in cytochrome C and PGC1alpha levels, suggesting perturbed energy production by mitochondria. The absence of alpha1AMPK also induced a reduction in histone deacetylase activity, which was associated with an increase in histone H3 acetylation (K9/K14 residues). Together, the results of the present study suggest that absence of AMPK, modifies oocyte quality through energy processes and oocyte/somatic cell communication. The limited effect observed in vivo could be partly due to a favourable follicle microenvironment where nutrients, growth factors, and adequate cell interaction were present. Whereas in a challenging environment such as that of in vitro culture following IVF, the phenotype is revealed. |
