Structural changes, increased hypoxia, and oxidative DNA damage in placenta due to maternal smokeless tobacco use

Smokeless tobacco (SLT) consumption during pregnancy is a well-recognized health risk that causes placental damage including hypoxia and oxidative damage. Although consumption of SLT by women varies from region to region, majority of tea leave pluckers consume SLT for relieving stress and pain. Still, the effects of SLT consumption have not been evaluated in tea garden workers (TGW). While previous studies have attempted to report effects of cigarette smoke using in vitro model, hypoxia-inducible factor (HIF)-1α expression in human placentae from pregnant women exposed to SLT has not been previously studied. This study was aimed to explore the effects of SLT consumption on placental structure, expression of HIF-1α and oxidative DNA damage in sample population of TGW.

A total of 51 placentae were collected from SLT users and nonusers (n = 30 and 21, respectively) with full-term normal delivery, who were involved in the plucking of tea leaves during pregnancy in tea plantation. Low birth weight (LBW, i.e., weight <2,500 g) and normal birth weight (NBW) groups among both SLT user and nonuser were compared for the stated parameters. Placental tissues were processed for transmission electron microscopy (TEM) study and immunohistochemical analysis for the expression of HIF-1α and 8-hydroxy-2'-deoxyguanosine (8-OHdG).

Altered ultrastructural characteristics were observed in the tertiary villi of LBW group among SLT users which included endothelial cells protrusion into capillary lumen, degenerated nuclei, significant thickening of trophoblast basement membrane and vasculo-syncytial membrane, abnormalities of the microvilli, swollen or damaged mitochondria, and dilatation in endoplasmic reticulum cisternae. Furthermore, significant reduction in the perimeter, area, and number of the stromal capillary of the tertiary villi of placenta were found in LBW group as compared with NBW group from the SLT users. Enhanced expression for HIF-1α and oxidative DNA damage (8-OHdG) biomarker was observed in SLT users as compared with nonusers.

Maternal SLT exposure during pregnancy may be associated with villus hypoxia and consequently oxidative DNA damage. It is presumed that deleterious effect of SLT exposure on placenta could result in impairment of placental barrier, and restrict nutrient and oxygen supply from mother to fetus, and thus could be a cause of fetal growth restriction.