Distinct roles for S100a8 in early embryo development and in the maternal deciduum

Area of Science:

• Reproductive biology
• Developmental biology
• Immunology

Background:

• S100a8 is a cytosolic protein typically found with S100a9 in myeloid cells.
• While S100a9 knockout mice are normal, S100a8 deficiency is embryonic lethal.
• The specific functions of S100a8 independent of S100a9 remain largely unexplored.

Purpose of the Study:

• To investigate the novel, S100a9-independent roles of S100a8.
• To elucidate S100a8's function in early embryonic development.
• To understand S100a8's contribution to placental and maternal decidual development.

Main Methods:

• Analysis of S100a8 expression patterns during early embryogenesis (up to E2.5).
• Examination of S100a8 localization in the maternal deciduum and its association with vasculature and uterine natural killer cells (E8.5 onwards).
• Assessment of S100a8's functions in chemoattraction and antioxidant activity in peripheral tissues.

Main Results:

• S100a8 demonstrates a critical, previously unrecognized role in embryo development from fertilization to the 8-cell stage (E2.5).
• S100a8 is expressed in the maternal deciduum's vasculature from E8.5 through placental maturation.
• Uterine natural killer cells involved in vascular remodeling colocalize with S100a8 in the metrial triangle.

Conclusions:

• S100a8 has at least two significant functions independent of S100a9 in early development.
• These roles include critical contributions to early embryogenesis and maternal-fetal interface development.
• S100a8's chemoattractant and antioxidant properties may be vital for placental development.