Heat Shock Proteins, Genital Tract Infections and Reproductive Outcome

Abstract

AbstractHeat shock proteins are among the first proteins produced by the fertilised ovum. Studies on in vitro cultured mouse and bovine embryos demonstrate that monoclonal antibodies to the 60 and 70 kDa heat shock proteins (Hsp60, Hsp70) inhibit early embryo development. Genital tract infections, especially chronic Chlamydia trachomatis infections of the Fallopian tubes, result in the generation of immunity to conserved regions that are present on both the chlamydial and human Hsp60 molecules. Women who are infertile due to tubal blockage who seek to become pregnant by in vitro fertilisation have reduced success rates if they are sensitised to conserved Hsp60 epitopes. In the mid-trimester of pregnancy, Hsp70 is present in amniotic fluid and may contribute to immune defence mechanisms to down-regulate the extent of inflammation in the amniotic cavity that may be deleterious to fetal development or may promote premature myometrial contractions. IgG antibody to Hsp70, produced by the mother in response to an altered stress-inducing environment and transferred across the placenta into the amniotic fluid, may positively potentiate the action of fetal Hsp70. A polymorphism in the fetal gene coding for the 47 kDa heat shock protein, most common in African Americans, has been associated with reduced collagen levels in fetal membranes and increased susceptibility to develop preterm premature rupture of membranes (pPROM). A polymorphism in the gene coding for the inducible Hsp70 may also increase the likelihood for pPROM in multifetal pregnancies. Quantitative measurement of heat shock proteins or heat shock protein antibodies during pregnancy may have value as early biomarkers for subsequent specific adverse outcomes.KeywordsHeat shock proteinsGenital infectionsPregnancyInfertilityGene polymorphisms