Rappolee Lab
Reproductive and developmental stress labs seek to enable the best pregnancies and resulting children by identifying stressors and their effects and by Measuring, Mechanism’s identification and then Managing stress: the 3M of our efforts.
6 things you should know about developmental stress:
1. Diet supplements can delay development or kill embryos and we have evidence for the mechanism.
2. CoQ10 improves reproduction in older females by rejuvenating oocytes and early embryos by decreasing stress and increasing energy and stem cell pluripotency.
3. Stress increases covid-19 susceptibility and decreases host cell viral resistance in embryonic stem cells as a model for early first trimester miscarriage and birth defects.
4. Transgenic embryonic stem cells report stress effects on embryonic growth and differentiation balance as well as miscarriage in high throughput screens.
5. Ranking IVF stress
6. Ranking environmental and maternal stressors
1. Diet supplements can be delay development or kill embryos and we have evidence for the mechanism.
Diet supplements are used in 1000’s of clinical trials to sensitive cancer stem cells to stop proliferation and much of this anti-proliferative activity is directed through the stress enzyme AMP-activated protein kinase (AMPK).
AMPK also detects low cellular ATP levels in all cells in the body, and thus is the energy sensor of the cell.
Reproductive stress labs have determined that AMPK is activated by many stressors, benzo(a)pyrene from cigarette smoke and diesel exhausts, hyperosmotic stress, and hypoxic stress.
But AMPK is also activated by all Diet supplements on the list of the US Office of Diet Supplements at NIH.
AMPK is also activated, and part of the therapeutic mechanisms of common drugs on the WHO (world health organizations) most prescribed and used list, aspirin, and metformin.
Aspirin, Metformin, and the diet supplement BR-DIM (from yellow cruciate vegetables) block early embryo growth while activating AMPK, whereas an AMPK inhibitor Compound C, reverses negative effects of drugs and diet supplements on embryos cultured in a similar way as in in vitro fertilization (IVF) clinics.
2. CoQ10 improves reproduction in older females by rejuvenating oocytes and early embryos by decreasing stress and increasing energy and stem cell pluripotency.
CoQ10 has increased ATP in culturing maturing oocytes in IVF and increased mitochondria mass and activity as well as pluripotency while decreasing oocyte death and AMPK activity indicating ATP depletion.
CoQ10 increases litter size in older pregnant female mice, in a model for increasing positive outcome of older fertile women who have delayed starting their families.
Giving more energy to early oocytes, embryos, and their stem cells, using the vitamin CoQ10, helps them solve many stress related, energy-depleting challenges in fertile women and in the treatment of embryos from infertile women undergoing IVF treatment.
3. Stress increases covid19 susceptibility and decreases host cell viral resistance in embryonic stem cells as a model for early first trimester miscarriage and birth defects.
Stress increases Covid19 susceptibility in embryonic stem cells as a model for the early first trimester embryo by increasing the receptors and surface processing genes that enable virus entrance into the host cell.
Stress decreases most genes in four recognized families that carry out host cell viral resistance, whereas most genes in these families increase with normal development.
4. Transgenic embryonic stem cells report stress effects on embryonic growth and differentiation balance as well as miscarriage in high throughput screens.
Embryonic stem cells that are transgenic for multiple reporter genes report in time lapse time- and dose-dependent which report developmental toxicity exposures of maternal stress hormones, PFAS family toxicants, Phthalate family toxicants, benzopyrenes and other volatile hydrocarbons, diet supplements, drugs, and IVF stressors.
5. Ranking IVF stress
Hyaluronidase removal of cumulus cells.
Pipetting: shear stress (acute, not chronic).
Historically older media (Hams F12, Whitten’s, ???)
Contradictory signals between incorrect O2 levels and growth factors for pluripotency or multipotency
6. Ranking environmental and maternal stressors
Faster, ESC More sensitive Greater magnitude
PFOA 26 1,000 10
DEP 1 1 1
ESC culture
7. Prioritized differentiation as the strategic adaptive response of ESC and TSC of the early embryo: what this means of pathogenic responses.