In summary, our data indicate that GDM is associated with overt neutrophil activity, resulting in placental infiltration, enhanced NET formation, and NE release. The latter has the potential to profoundly alter placental cell biology via the enzymatic degradation of key regulatory signal transduction components. In addition, our findings on overt neutrophil activity may pave the way for more precise screening tools to assist with the detection of GDM than the current challenge with HG levels, which have limited utility and lack international standardization (50, 57, 58, 59).