EFFECT OF PREECLAMPSIA INDUCED PRENATAL HYPOXIA ON INFANT T REGULATORY CELL RELATED GENE EXPRESSION

Introduction :

Preeclampsia with a prevalence of 0.2 to 6.7 % in Asia, is an important pregnancy related hypertensive disorder which contributes to pregnancy related morbidity and mortality and long term complications for both the mother and the child. Clinically preeclampsia presents as increased blood pressure and proteinuria. This is a result of abnormal placentation and improper adhesion of the trophoblasts leading to reduced maternal blood flow. Exposure to preeclampsia is associated with poorer outcomes for the infant in the postnatal period such as low birth weight and lower APGAR scores. This is primarily due to decreased blood circulation leading to prenatal hypoxia.

Studies have found that decreased T regulatory cells (Treg) population in uterine tissue is associated with preeclampsia.

Treg cells play an important role in facilitating implantation, mediating foetal tolerance. They  also play an important role in the pathogenesis of many autoimmune and inflammatory disorders. Treg cell expression is characterised primarily by expression of transcription factor FOXP3 followed by related genes including CTLA4 and GATA3 essential for induction and maintenance of FOXP3 expression.

 In cases of exposure to hypoxia, the infant immune landscape may be adversely affected because of the induction of factors associated with hypoxia potentially leading to a generally increased inflammatory profile. The exact effect of prenatal hypoxia on the expression of FOXP3 and other immune markers associated with Treg cells is still not completely understood.(11) It is important to identify the effect of hypoxic conditions on the infants genes related to Treg development and function. Dysregulation of these gene expressions may potentially lead to increased susceptibility to autoimmune conditions. Through our study we would like to understand this aspect of preeclampsia complicated pregnancy. The study of genes associated with Treg cells other than FOXP3 will further provide novel insights into the molecular mechanisms in action

Objective

1. To determine the effect of preeclampsia induced prenatal hypoxia on T Regulatory cell-related gene expression in the infant cord blood.

2. To find a correlation between PO2, PCO2, lactate levels, bicarbonate levels and FOXP3, CTLA4 and GATA3 gene expression.

The results obtained through this study will help us better understand the immune dysregulation of the infant caused by exposure to prenatal hypoxia due to preeclampsia. By investigating impaired Treg cell expression, we can better understand its link to autoimmune disorders. This study provides novel insights into preeclampsia and will further lead to identification of future therapeutic targets for treatment of prenatal hypoxia related immune dysregulation in the infant. The results will inform public health policy in regard to maternal and child health and guide future research in this area.