According to the doctoral thesis by Ali Mohammed, MSc in Toxicology, fetal exposure to diuron is possible, if the pregnant mother is exposed. Diuron is globally a commonly used herbicide. The thesis shows also that various chemicals can change placental metabolism which is critical for fetal growth and development.
Exposure to chemicals is inevitable, and all people including pregnant women, are exposed continuously throughout their lifetime. Fetal period is the most sensitive time of life to the effects of chemicals and thus exposure of pregnant women is most harmful. One of the most important routes of exposure, especially to pesticides, such as diuron, is drinking water. In aquatic organisms diuron is toxic to reproductive organs and during development. In addition, it is carcinogenic in rat. Toxicity of diuron to human is practically unknown.
In this thesis transplacental transfer and metabolism of diuron was studied in human placental perfusion, a model where a piece of placenta is kept functional by artificial circulation. Diuron crossed easily human placenta suggesting fetal exposure if the pregnant mother is exposed. In placenta diuron was metabolized to a toxic metabolite, DCPMU (dichlorophenyl methyl urea). Taking into account the transplacental transfer of diuron, and the toxicity of diuron and DCPMU in animals, and the fact that fetus is especially sensitive to toxicity, exposure to diuron during pregnancy may lead to developmental aberrations also in human. Toxicity of diuron and its metabolites were also studied in BeWo cells originating from human trophoblastic cancer, and other cell lines representing human tissues. Among these, BeWo cells were the most sensitive indicating that placental tissue is more sensitive than other human tissues to diuron toxicity.
Stored placental tissue samples from earlier perfusions were used to analyze several xenobiotic and hormone metabolizing enzymes as well as enzymes against oxidative stress. Samples taken before the perfusions were compared to the ones taken after. Several chemicals studied in the perfusions changed placental enzyme activities. Chemical exposure during pregnancy can thus lead to disturbance of placental function and possibly to aberrations in fetal development.
The results of this thesis raise concerns about the toxicity of diuron to human fetus if the mother is exposed. Also, other chemicals may be toxic in placenta. This study further endorses usability of human placental perfusion as a tool for predicting fetal exposure, and metabolism and toxicity of chemicals in human placenta.
The doctoral dissertation of Ali Mohammed, Master of Science (Toxicology), entitled Toxicokinetics and toxicity related mechanisms of xenobiotics in human placenta, will be examined at the Faculty of Health Sciences. The Opponent in the public examination will be Docent Mikko Koskinen from Orion Pharma, and the Custos will be Professor Emerita Kirsi Vähäkangas from the University of Eastern Finland. The public examination will be held in English on the 31st of October 2020.
Photo available for download at https://mediabank.uef.fi/A/UEF+Media+Bank/37804?encoding=UTF-8
Thesis available online: http://urn.fi/URN:ISBN:978-952-61-3497-0
