Expression of 8-oxoguanine glycosylase in human fetal membranes

Abstract

Problem: The most common DNA lesion generated by oxidative stress (OS) is 7, 8-dihydro-8-oxoguanine (8-oxoG) whose excision repair is performed by 8-oxoguanine glycosylase (OGG1). We investigated OGG1 expression changes in fetal membranes from spontaneous preterm birth (PTB) and preterm premature rupture of the membranes (pPROM) and its changes in vitro in normal fetal membranes exposed to OS inducer water-soluble cigarette smoke extract (CSE).

Method of study: DNA damage was determined in amnion cells treated with CSE by comet and FLARE assays. OGG1 mRNA expression and localization in fetal membranes from clinical specimens and in normal term membranes exposed to CSE were examined by QRT-PCR and by immunohistochemistry.

Results: DNA strand and base damage was seen in amnion cells exposed to CSE. OGG1 expression was 2.5-fold higher in PTB samples compared with pPROM (P = 0.045). No significant difference was seen between term and pPROM or PTB and term. CSE treatment showed a nonsignificant decrease in OGG1. OGG1 was localized to both amnion and chorion with less intense staining in pPROM and CSE-treated membranes.

Conclusion: Increased OS-induced DNA damage predominated by 8-oxoG is likely to persist in fetal cells due to reduced availability of base excision repair enzyme OGG1. This can likely lead to fetal cell senescence associated with some adverse pregnancy outcome.

Keywords: Base excision repair; DNA damage; DNA repair; oxidative stress; prematurity; preterm premature rupture of the membranes.