The doctoral thesis of Rami El-Dairi, MSc, provides novel information about placental gene expression and insights into how chemicals may disrupt normal placental physiological functions in pregnant women. In this thesis, novel target genes were identified in human placental trophoblasts in response to pioglitazone, β-naphoflavone (BNF) and aflatoxin B1 (AFB1).
Various chemicals such as pharmaceuticals and environmental contaminants can alter placental gene expression causing adverse effects on fetal development. The placenta is a transitory organ that regulates the passage of endogenous and xenobiotic compounds between the mother and the fetus during pregnancy. The human placenta has unique tissue-specific properties including a distinct set of transcription factors that are highly expressed in placenta such as peroxisome proliferator-activated receptor γ (PPARγ) and aryl hydrocarbon receptor (AhR). However, the target genes of these two transcription factors are almost unknown in human placenta. A common food contaminant AFB1 is a fungal metabolite that is toxic to humans with the liver as its major target organ but its effects on human placenta are not well known.
In this thesis, the effects of a PPARγ-agonist pioglitazone, an AhR-agonist, BNF and AFB1 were investigated on transcriptional responses in cultured human primary trophoblasts. The trophoblasts were isolated from full term placentas after delivery and were exposed to pioglitazone, BNF or AFB1. Placental gene expression profiles were characterized, and the gene regulatory networks and molecular pathways were computationally analysed among the dysregulated genes.
In summary, the results of this thesis revealed that pioglitazone and BNF regulated especially genes involved in cellular growth and invasion, the inflammatory response, as well as lipid metabolism and cholesterol uptake, whereas AFB1 affected genes related to placental growth, endocrine signalling, energy homeostasis and cell cycle regulation in primary trophoblasts.
This study belongs to the studies carried out by Kuopio Birth Cohort consortium (KuBiCo), which is a joint research project between University of Eastern Finland, Department of Obstetrics and Gynecology in Kuopio University Hospital and National Institute of Health and Welfare (THL).
The doctoral dissertation of Rami El-Dairi, Master of Science (Toxicology), entitled “Effects of pioglitazone, β-naphthoflavone and aflatoxin B1 on gene expression profiles in human trophoblasts in vitro” will be examined at the Faculty of Health Sciences. The opponent in the public examination will be docent Siri Lehtonen, Ph.D., of the Oulu University Hospital, and the custos will be Professor Jaana Rysä of the University of Eastern Finland. The public examination will be held in English and it can be followed online on the 21st of June 2021 starting at 12 noon.