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A Major Effect of Simulated Microgravity on Several Stages of Preimplantation Mouse Development is Lethality Associated With Elevated Phosphorylated SAPK/JNK

Department of Obstetrics and Gynecology, C. S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, Michigan

Yufen Xie, MD

Department of Obstetrics and Gynecology, C. S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, Michigan

Dana Wygle, MS

Department of Obstetrics and Gynecology, C. S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, Michigan

Hayley H. Shen, PhD

Department of Civil & Environmental Engineering Clarkson University Potsdam, New York

Elizabeth E. Puscheck, MD

Department of Obstetrics and Gynecology, C. S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, Michigan

Daniel A. Rappolee, PhD

Departments of Reproductive Sciences, Physiology, Wayne State University School of Medicine, drappole{at}med.wayne.edu, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, Institute for Environmental Health and Safety, Wayne State University School of Medicine, Detroit, Michigan, Department of Biological Sciences, University of Windsor, Ontario, Canada

We tested whether microgravity affects mouse development during a period when gravity cues chick and frog embryo development. A rotating vessel developed ~ 0.1% simulated microgravity (MGS) for embryos. Microgravity simulation resulted in blocked cell accumulation in E2.5 embryos. E1.5 and E3.5 embryos showed lesser effects. For E1.5/2.5 embryos, cell accumulation block was followed by lethality at 48 hours after MGS. For E3.5 embryos, MGS blocked development without lethality but with apoptosis. E1.5-3.5 embryos from the rotational control developed lesser effects than MGS embryos. Embryonic stress-activated protein kinase (SAPK) was phosphorylated during MGS and mediated apoptosis. Increased pSAPK suggested that lethality is due to cellular stress induced by MGS, unlike the dysfunctional development after gravitational disorientation in frog and chick embryos. Thus, MGS causes lethality, a novel phenotype not often observed in microgravity or MGS. Embryonic lethality at E2.5 and apoptosis at E3.5 are associated with SAPK function, suggesting that MGS causes a general stress response that immediately affects many aspects of development. In addition, MGS and many aspects of In vitro fertilization/assisted reproductive technologies (IVF/ART) produce nonphysiological, nonevolutionary stresses that are mediated by SAPK, suggesting the primacy of this protein kinase in a wide range of mechanisms mediating negative reproductive outcomes in IVF/ART and potentially in spaceflight.

Key Words: Microgravity • preimplantation • signal transduction • stress activated protein kinase (SAPK/JNK) • trophoblast.

This version was published on October 1, 2009

Reproductive Sciences, Vol. 16, No. 10, 947-959 (2009)
DOI: 10.1177/1933719109337544


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