Molecular control of mitochondrial function in developing rhesus monkey oocytes and preimplantation-stage embryos
N. R. Mtango A E , A. J. Harvey C E , K. E. Latham A B and C. A. Brenner C D FA The Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
B Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA 19140, USA.
C Department of Physiology, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
D Department of Obstetrics and Gynecology, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
E These authors contributed equally to this study.
F Corresponding author. Email: cbrenner@med.wayne.edu
Reproduction, Fertility and Development 20(7) 846-859 https://doi.org/10.1071/RD08078
Submitted: 18 April 2008 Accepted: 21 July 2008 Published: 16 September 2008
Abstract
The mitochondrion undergoes significant functional and structural changes, as well as an increase in number, during preimplantation embryonic development. The mitochondrion generates ATP and regulates a range of cellular processes, such as signal transduction and apoptosis. Therefore, mitochondria contribute to overall oocyte quality and embryo developmental competence. The present study identified, for the first time, the detailed temporal expression of mRNAs related to mitochondrial biogenesis in rhesus monkey oocytes and embryos. Persistent expression of maternally encoded mRNAs was observed, in combination with transcriptional activation and mRNA accumulation at the eight-cell stage, around the time of embryonic genome activation. The expression of these transcripts was significantly altered in oocytes and embryos with reduced developmental potential. In these embryos, most maternally encoded transcripts were precociously depleted. Embryo culture and specific culture media affected the expression of some of these transcripts, including a deficiency in the expression of key transcriptional regulators. Several genes involved in regulating mitochondrial transcription and replication are similarly affected by in vitro conditions and their downregulation may be instrumental in maintaining the mRNA profiles of mitochondrially encoded genes observed in the present study. These data support the hypothesis that the molecular control of mitochondrial biogenesis, and therefore mitochondrial function, is impaired in in vitro-cultured embryos. These results highlight the need for additional studies in human and non-human primate model species to determine how mitochondrial biogenesis can be altered by oocyte and embryo manipulation protocols and whether this affects physiological function in progeny.
Additional keywords: gene regulation, macaque, mitochondrial DNA transcription factors.
Acknowledgements
The authors thank Bela Patel, Malgorzata McMenamin, Judy Procknow and Ann Marie Paprocki for their technical assistance. The authors also thank R. Dee Schramm for his contribution to the development of the PREGER resource. This work was supported by a research resource grant from the National Centers for Research Resources (RR15253) and CA95569 to K.L. and a National Centers for Research Resources grant (RR021881) to C.B.
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