Stem Cell Reviews and Reports

, Volume 13, Issue 4, pp 454–464 | Cite as

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

  • Yu Yang
  • Alan Bolnick
  • Alexandra Shamir
  • Mohammed Abdulhasan
  • Quanwen Li
  • G. C. Parker
  • Elizabeth E. Puscheck
  • D. A. Rappolee


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.


Metabolism Embryonic stem cells Trophoblast stem cells Stress Transcription factors Potency Differentiation Proliferation 



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).

Compliance with Ethical Standards

Grants Support

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.

Conflicts of Interest

The authors declare no potential conflicts of interest.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Yu Yang
    • 1
    • 2
  • Alan Bolnick
    • 1
  • Alexandra Shamir
    • 3
  • Mohammed Abdulhasan
    • 1
  • Quanwen Li
    • 1
    • 4
  • G. C. Parker
    • 4
    • 5
  • Elizabeth E. Puscheck
    • 1
  • D. A. Rappolee
    • 1
    • 2
    • 4
    • 6
  1. 1.CS Mott Center for Human Growth and Development, Department of Ob/Gyn, Reproductive Endocrinology and InfertilityWayne State University School of MedicineDetroitUSA
  2. 2.Program for Reproductive Sciences and Department of PhysiologyWayne State University School of MedicineDetroitUSA
  3. 3.University of UtahSalt Lake CityUSA
  4. 4.Institutes for Environmental Health ScienceWayne state University School of MedicineDetroitUSA
  5. 5.Department of Pediatrics and Children’s Hospital of MichiganWayne State University School of MedicineDetroitUSA
  6. 6.Department of BiologyUniversity of WindsorWindsorCanada

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