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Effects of Lactate Concentration in the IVF Media


The phenotype of the human embryo conceived through in vitro fertilization (IVF) can be affected by the media that the embryo is cultured in.  Even small changes in the culture media constituents can affect things like embryonic morphology, developmental kinetics, physiology, and metabolism.  In particular, factors such as oxygen, temperature, metabolic substrates and pH, have all been shown to modify embryonic outcomes.  Importantly, different IVF clinics use completely different media, and often refuse to disclose the constituents.  It is therefore important to study the effects of culture media on embryonic outcomes in order to develop optimal conditions for IVF practices.  This study is particularly interested in the effects of lactate and pyruvate concentration in the media.

How does Lactate Effect Embryonic Development?

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  • One of the basic components in culture media reportedly included to promote embryo development are energy substrates. Pyruvate and lactate are the early embryo's primary source of energy, and their utilization continues throughout preimplantation development. Pyruvate enters the Krebs cycle directly, whereas lactate must first be converted to pyruvate by lactate dehydrogenase before entry into this cycle. The interconversion between lactate and pyruvate and the associated consumption and production of NAD+ and NADH play a critical role in controlling metabolism and maintaining an appropriate reductive-oxidative (REDOX) balance in the embryo. 

  • Thus, it is not only the absolute concentration of lactate and pyruvate in the culture medium but also the ratio of these two carbohydrates that may be the most influential to embryo viability.

  • In humans, the lactate/pyruvate (L:P) ratio is reported to be approximately 33 in oviductal fluid, and approximately 59 in uterine fluid. However, studies have reported widely disparate L:P ratios present in the commercial media tested. For early cleavage-stage embryos this ratio varied from 8 to 126. The post-compaction environment was also variable, with L:P ratios ranging from 24 to 104.

  • A high L:P ratio is concerning for several reasons. In mice, increasing amounts of lactate in the medium decrease pyruvate oxidation, which is the primary source of energy for embryos at this stage. In addition, the ability to utilize lactate is not obtained until after the first cleavage division unless aspartate is present. Finally, only exogenous pyruvate is metabolized in the mitochondria to provide adenosine triphosphate, whereas lactate-derived pyruvate is not; however, mouse embryos can develop with lactate as the sole carbohydrate energy source if aspartate is provided. A very low L:P ratio may also be of concern because pyruvate is a cytosolic oxidant and can result in an overly oxidative environment.
    •    It is known from embryo transfer studies that a lactate gradient impacts embryo viability. However, there is a paucity of data regarding the effects of lactate on the cardiovascular phenotype. Hence, we are researching on the role of nutrient gradients particularly lactate in regulating the embryo cardiac phenotype.
    •    The techniques we use to study this include: Blastocyst differential staining, Imaging, ultramicrofluorometric assays, RESIPHER etc.

Relevant Papers

Padhee M, Zhang S, Lie S, Wang KC, Botting KJ, McMillen IC, MacLaughlin SM, Morrison JL. The periconceptional environment and cardiovascular disease: does in vitro embryo culture and transfer influence cardiovascular development and health? Nutrients. 2015 Feb 18;7(3):1378-425. doi: 10.3390/nu7031378. PMID: 25699984; PMCID: PMC4377860.

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