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Reproductive Sciences
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What's this?

Integrin β-4 Signaling Plays a Key Role in Mouse Embryogenesis

Jeffrey E. Roberts, MD

Pacific Centre for Reproductive Medicine, Burnaby, British Columbia, Canada

Sotiris N. Nikolopoulos, PhD

Cellular Biochemistry & Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York

Ozgur Oktem, MD

Departments of Obstetrics and Gynecology, New York Medical College, Valhalla, New York and Center for Human Reproduction, New York

Filippo Giancotti, MD, PhD

Cellular Biochemistry & Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York

Kutluk Oktay, MD, FACOG

Departments of Obstetrics and Gynecology, New York Medical College, Valhalla, New York and Center for Human Reproduction, New York, koktay{at}fertilitypreservation.org

Integrins, by signaling between extracellular matrix and cell nucleus, serve critical roles in cell proliferation and survival. A knock-in mice was developed by a targeted deletion of the C-terminal segment of the cytoplasmic tail of β4-integrin (β4-1355T). The β4-1355T mice had a longer gestational length, smaller litter sizes, lower fecundity rate, and higher frequency of early pregnancy loss. β4-1355T embryos demonstrated a high degree of fragmentation and asymmetry, with fewer surviving to either a morula or blastocyst stage. In wild-type oocytes and embryos, β1, β4, and laminin-5 signals colocalized at the opposing surfaces of blastomeres and between the polar bodies and oocytes. Blastomeres within the β4-1355T embryos were less cohesive, with a more diffuse expression of β4 and laminin-5 compared with wild type. The {alpha}6β4_laminin-5 interaction appears to be vital for maintaining the cohesiveness between the cells of the embryo. Deciphering the role of integrins such as β4 in embryogenesis may help explain in vitro fertilization failures.

Key Words: β4-integrin • knock-in • mouse • embryogenesis • reproduction • implantation.

This version was published on March 1, 2009

Reproductive Sciences, Vol. 16, No. 3, 286-293 (2009)
DOI: 10.1177/1933719108325506
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