title: Prematuration with cyclic adenosine monophosphate modulators alters cumulus cell and oocyte metabolism and enhances developmental competence of in vitro-matured mouse oocytes.
abstract: Oocyte in vitro maturation (IVM) is an important assisted reproductive technology and research tool. The adoption of IVM into routine clinical practice has been hindered by its significantly lower success rates compared to conventional in vitro fertilization. Cyclic AMP (cAMP) modulation and follicle-stimulating hormone (FSH), independently, have long been known to improve IVM oocyte developmental competence. This study comprehensively examined the effects of FSH and cAMP/cGMP modulation, alone and in combination, on IVM oocyte metabolism and developmental outcomes. Mouse cumulus-oocyte complexes (COCs) were subjected to a 1 h prematuration phase ± the cAMP modulator forskolin and cAMP/cGMP modulator 3-isobutyl-1-methylxanthine followed by IVM ± FSH. Prematuration with these cyclic nucleotide modulators or IVM with FSH significantly improved oocyte developmental competence and reduced spindle abnormalities compared to spontaneous IVM (no treatment); however, these two treatments in combination endowed even greater developmental competence (improved subsequent blastocyst rates and quality; P < 0.05), albeit blastocyst yield and quality remained significantly lower than that of oocytes matured in vivo. A significant additive effect of combined IVM treatments was evident as increased COC lactate production and oxygen consumption and enhanced oocyte oxidative metabolism, ATP production, ATP:ADP ratio, and glutathione levels (P < 0.05). Nevertheless, IVM increased reactive oxygen species production, particularly as a consequence of FSH addition, relative to in vivo matured oocytes. In conclusion, improvements in the embryo yield following IVM is associated with increased COC oxygen consumption and oocyte oxidative metabolism, but these remain metabolically and developmentally less competent relative to in vivo derived oocytes.
authors: Research Centre for Reproductive Health, Robinson Institute, and Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia Center for Reproductive Medicine, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Hai-Tao
authors: HT
authors: Zeng
authors: Research Centre for Reproductive Health, Robinson Institute, and Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia.
authors: Dulama
authors: D
authors: Richani
authors: Research Centre for Reproductive Health, Robinson Institute, and Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia.
authors: Melanie L
authors: ML
authors: Sutton-McDowall
authors: Research Centre for Reproductive Health, Robinson Institute, and Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia Center for Reproductive Medicine, General Hospital of Guangdong, Guangzhou, People's Republic of China.
authors: Zi
authors: Z
authors: Ren
authors: Follicle Biology Laboratory, Center for Reproductive Medicine and Medical School, Free University Brussels (VUB), Brussels, Belgium.
authors: Johan E J
authors: JE
authors: Smitz
authors: School of Mathematical Science, The University of Adelaide, Adelaide, South Australia, Australia.
authors: Yvonne
authors: Y
authors: Stokes
authors: Research Centre for Reproductive Health, Robinson Institute, and Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia.
authors: Robert B
authors: RB
authors: Gilchrist
authors: Research Centre for Reproductive Health, Robinson Institute, and Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia jeremy.thompson@adelaide.edu.au.
authors: Jeremy G
authors: JG
authors: Thompson
mesh_terms: D000818:Animals; D001755:Blastocyst; D054885:Cumulus Cells / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000037:antagonists & inhibitors*; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D059471:In Vitro Oocyte Maturation Techniques; D051379:Mice; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption
chemical_list: D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP
keywords: ATP; FSH; IVM; cAMP; glycolysis; mitochondria; oocyte metabolism