AMPK agonist drugs and diets supplements cause more harm to 2-cell embryos than blastocysts

What is it about?

Stress causes a small subset of the stress protein kinases in the kinome to decrease anabolism, proliferation and potency/stemness in a wide range of stem cells. One kinase associated and causal to anabolism and stemness loss is AMP-activated protein kinase (AMPK). However all diet supplements tested to date also activated AMPK as do many commonly used drugs such as aspirin and metformin. Thus many compounds not associated with stress, but activating AMPK as does stress, may also slow growth in early post-fertilization embryos at 2-cell and 64-cell (blastocyst) stages. We show here that, for block of anabolism and potency loss, totipotent 2-cell embryos are more sensitive (have larger effects) than pluripotent and multipotent stem cells of the blastocysts.

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Why is it important?

This is important as fertile age women often use drugs and diets supplements and also are exposed to stimuli that cause stress. At the time of highest growth in the mammalian life history, it is important to maintain growth so that sufficient stem cells arise and the sufficient first lineage differentiated function arises to gain maternal nutrition needed for rapid growth. Diet supplement, drugs and stress slow growth, force differentiation and this can kill the embryo directly or indirectly by depleting stem cells. Two thirds of all human embryos miscarry after fertilization and the majority of miscarriage is during the period of exponential growth. Interestingly if diet supplements and/or drugs or stress blocked anabolism, proliferation, and potency at the 2-cell stage embryo, miscarriage would occur before pregnancy was detected by hormone tests. About 1/3 of all fertilized embryos are lost before detection in humans and these data suggest the possibility that AMPK agonists could contribute to this large fraction of loss. This needs to be tested in vivo.

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