Placenta in Health and Disease - research projects

Figure-5.pngOur international and interdisciplinary research group is interested in prenatal development with the main focus on the neuroplacentology and placenta-brain axis. The team’s expertise extends from placental biology, genetics, biochemistry, physiology, to the clinical research field. Numerous epidemiological studies have linked prenatal use of pharmacotherapy or drugs of abuse with neurological diseases of the offspring, including, but not limited to, autism spectrum disorder, schizophrenia, depression. Nonetheless, the causal mechanisms remain largely unexplained. Through understanding the complexity of placental biology, our goal is to decipher how endocrine disruptors (EDs) used in pregnancy – such as pharmaceuticals, xenobiotics, illicit drugs - affect the placental homeostatic mechanisms and communication on the placenta-brain axis. Our team was the first to report Organic Cation Transporter 3 (OCT3/SLC22A3) as a novel component of the fetoplacental homeostasis of monoamines (Acta Physiologica 2020, awarded the Carl Ludwig Award by the Scandinavian Physiological Society in September 2021).

In our follow up studies, we have demonstrated that this placental clearance system may be compromised by prenatal exposure to endocrine disruptors, including antidepressant drugs (Pharmaceutics, 2021), thus representing a molecular target for impaired prenatal monoamine signaling. In addition, we have recently delineated the tryptophan catabolic routes within the placenta-brain axis (Front. Cell Dev.Fig-11-(updated).png Biol., 2020, Int. J. Mol. Sci. 2020), which is of crucial importance due to the neuroactive nature of its metabolites (e.g., serotonin, melatonin, kynurenic acid, quinolinic acid) with the potential to affect fetal brain development in utero. These physiologically oriented studies proved a significant translational potential and in our follow-up clinical studies we demonstrated a link between maternal inflammation and disrupted fetoplacental homeostasis of tryptophan catabolism (Human Molecular Genetics, 2021), representing a potential mechanism involved in fetal programming of neurodevelopmental disorders.

Apart from monoamines and tryptophan homeostasis, we have newly extended our focus on further endocrine functions of the placenta, including steroid hormones and endocannabinoid system – mechanisms reportedly essential for the proper development and programming of the fetus. Importantly, our studies address the timing of insult during pregnancy as a critical element influencing fetal and postnatal brain development and programming.

 

© Charles University, Faculty of Pharmacy in Hradec Králové, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic
Website information | Powered by Kentico