Pretreatment with Pancaspase Inhibitor (Z-VAD-FMK)‎ Delays but Does Not Prevent Intraperitoneal Heat-Killed Group B Streptococcus-Induced Preterm Delivery in a Pregnant Mouse Model

Abstract EN

Caspases and apoptosis are thought to play a role in infection-associated preterm-delivery.

We have shown that in vitro treatment with pancaspase inhibitor Z-VAD-FMK protects trophoblasts from microbial antigen-induced apoptosis.

Objective.

To examine whether in vivo administration of Z-VAD-FMK would prevent infection-induced preterm-delivery.

Methods.

We injected 14.5 day-pregnant-mice with heat-killed group B streptococcus (HK-GBS).

Apoptosis within placentas and membranes was assessed by TUNEL staining.

Calpain expression and caspase-3 activation were assessed by immunohistochemistry.

Preterm-delivery was defined as expulsion of a fetus within 48 hours after injection.

Results.

Intrauterine (i.u.) or intraperitoneal (i.p.) HK-GBS injection led to preterm-delivery and induced apoptosis in placentas and membranes at 14 hours.

The expression of calpain, a caspase-independent inducer of apoptosis, was increased in placenta.

Treatment with the specific caspase inhibitor Z-VAD-FMK (i.p.) prior to HK-GBS (i.p.) delayed but did not prevent preterm-delivery.

Conclusion.

Caspase-dependent apoptosis appears to play a role in the timing but not the occurrence of GBS-induced preterm delivery in the mouse.