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Blastocyst-Derived Stem Cell Populations under Stress: Impact of Nutrition and Metabolism on Stem Cell Potency Loss and Miscarriage

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Abstract

Data from in vitro and in vivo models suggest that malnutrition and stress trigger adaptive responses, leading to small for gestational age (SGA) blastocysts with fewer cell numbers. These stress responses are initially adaptive, but become maladaptive with increasing stress exposures. The common stress responses of the blastocyst-derived stem cells, pluripotent embryonic and multipotent placental trophoblast stem cells (ESCs and TSCs), are decreased growth and potency, and increased, imbalanced and irreversible differentiation. SGA embryos may fail to produce sufficient antiluteolytic placental hormone to maintain corpus luteum progesterone secretion that provides nutrition at the implantation site. Myriad stress inputs for the stem cells in the embryo can occur in vitro during in vitro fertilization/assisted reproductive technology (IVF/ART) or in vivo. Paradoxically, stresses that diminish stem cell growth lead to a higher level of differentiation simultaneously which further decreases ESC or TSC numbers in an attempt to functionally compensate for fewer cells. In addition, prolonged or strong stress can cause irreversible differentiation. Resultant stem cell depletion is proposed as a cause of miscarriage via a “quiet” death of an ostensibly adaptive response of stem cells instead of a reactive, violent loss of stem cells or their differentiated progenies.

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Acknowledgements

We acknowledge funding from the Office of the Vice President for Research at Wayne State University, NIH (1R03HD061431) and the Kam Moghissi Endowed chair (EEP) and support for GCP and DR from NIH (P30 ES020957).

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Authors and Affiliations

  1. CS Mott Center for Human Growth and Development, Department of Ob/Gyn, Reproductive Endocrinology and Infertility, Wayne State University School of Medicine, 275 East Hancock, Detroit, MI, 48201, USA

    Yu Yang, Alan Bolnick, Mohammed Abdulhasan, Quanwen Li, Elizabeth E. Puscheck & D. A. Rappolee

  2. Program for Reproductive Sciences and Department of Physiology, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    Yu Yang & D. A. Rappolee

  3. University of Utah, 201 Presidents Circle, Salt Lake City, UT, 84112, USA

    Alexandra Shamir

  4. Institutes for Environmental Health Science, Wayne state University School of Medicine, Detroit, MI, 48201, USA

    Quanwen Li, G. C. Parker & D. A. Rappolee

  5. Department of Pediatrics and Children’s Hospital of Michigan, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    G. C. Parker

  6. Department of Biology, University of Windsor, Windsor, ON, N9B 3P4, Canada

    D. A. Rappolee

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  1. Yu Yang
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Correspondence to D. A. Rappolee.

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This research was supported by grants to DAR from NIH (1R03HD061431) and from the Office of the Vice President for Research at Wayne State University.

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Yang, Y., Bolnick, A., Shamir, A. et al. Blastocyst-Derived Stem Cell Populations under Stress: Impact of Nutrition and Metabolism on Stem Cell Potency Loss and Miscarriage. Stem Cell Rev and Rep 13, 454–464 (2017). https://doi.org/10.1007/s12015-017-9734-4

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  • DOI: https://doi.org/10.1007/s12015-017-9734-4

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