Glycolysis in preimplantation development is partially controlled by the Warburg Effect.
Glucose metabolism in preimplantation embryos has traditionally been viewed from a somatic cell viewpoint. Here, we show that gene expression in early embryos is similar to rapidly dividing cancer cells. In vitro-produced pig blastocysts were subjected to deep-sequencing, and were found to express two gene variants that have been ascribed importance to cancer cell metabolism (HK2 and the M2 variant of PKM2). Development was monitored and gene expression was quantified in additional embryos cultured in low or high O(2) (5% CO(2), 5% O(2), 90% N(2) vs. 5% CO(2) in air). Development to the blastocyst stage in the two atmospheres was similar, except low O(2) resulted in more total and inner cell mass nuclei than high O(2). Of the 15 candidate genes selected that are involved in glucose metabolism, only TALDO1 and PDK1 were increased in the low O(2) environment. One paradigm that has been used to explain glycolysis under low oxygen tension is the Warburg Effect (WE). The WE predicts that expression of both HK2 and PKM2 M2 results in a slowing of glucose metabolism through the TCA cycle, thereby forcing the products of glycolysis to be metabolized through the pentose phosphate pathway and to lactic acid. This charging of the system is apparently so important to the early embryo that redundant mechanisms are present, that is, a fetal form of PKM2 and high levels of PDK1. Here, we set the framework for using the WE to describe glucose metabolism and energy production during preimplantation development.
Division of Animal Science, University of Missouri, Columbia, Missouri 65211, USA.
Bethany K
BK
Redel
Alana N
AN
Brown
Lee D
LD
Spate
Kristin M
KM
Whitworth
Jonathan A
JA
Green
Randall S
RS
Prather
D000818:Animals; D001755:Blastocyst / Q000378:metabolism*; D018929:Cell Culture Techniques; D018507:Gene Expression Regulation, Developmental; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis; D045022:Lactate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D009385:Neoplastic Processes; D010100:Oxygen / Q000378:metabolism*; D011770:Pyruvate Kinase / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013552:Swine
D051246:Glucose Transport Proteins, Facilitative; D045022:Lactate Dehydrogenases; D011770:Pyruvate Kinase; D010100:Oxygen