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

Infect Dis Obstet Gynecol. 2009;2009:749432. doi: 10.1155/2009/749432. Epub 2009 Dec 28.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Calpain / metabolism
  • Caspase Inhibitors*
  • Caspases / metabolism
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Disease Models, Animal
  • Extraembryonic Membranes / metabolism
  • Extraembryonic Membranes / microbiology
  • Female
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Mice
  • Ovarian Follicle / metabolism
  • Ovarian Follicle / microbiology
  • Placenta / metabolism
  • Placenta / microbiology
  • Pregnancy
  • Premature Birth / enzymology
  • Premature Birth / microbiology*
  • Premature Birth / prevention & control*
  • Streptococcal Infections / complications*
  • Streptococcal Infections / drug therapy
  • Streptococcal Infections / microbiology
  • Streptococcus agalactiae / physiology*

Substances

  • Amino Acid Chloromethyl Ketones
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • Calpain
  • Caspases