Albrecht’s project 9B is dedicated to the identification of novel therapeutic targets proteins whose dysfunction at the materno-fetal interface might play an important role in the pathogenesis of pregnancy related diseases such as preeclampsia (PE), intrauterine growth restriction (IUGR) and gestational diabetes.
To this end the combination of in silico data analysis and screening of literature data is expected to result in the identification of several potentially therapeutically interesting transporters, some of them being already targets within the NCCR network in the context of other tissues and diseases. The therapeutic potential of those selected transporters will then be validated by qRT-PCR analysis using an in-house cDNA placental tissue bank. The validation of targets is based on the analysis of variance to verify the alteration of the gene expression in placenta tissues comprised of samples from PE, IUGR, or gestational diabetes, as compared to healthy control preterm and term placenta. This should lead to the identification of transporters being significantly altered in their expression in pregnancy-related diseases. After confirming these findings on the protein level, the link between differential expression (e.g. induced by hypoxia or nutrient availability) and altered placental substrate transport activity will be investigated in vitro and ex vivo. Regarding the latter, the group currently establishes the dual perfusion model of the human placenta that is useful for the assessment of the transport of various substrates across the materno-fetal interface. This ex vivo technique enables retention of a high level of structural organization of the placental tissue and better approximates to the in vivo state. The dual perfusion model will be used to complement cell based transport systems and to monitor the transport activity in healthy control versus pathological pregnancies and also under experimental stress conditions, such as oxidative stress and ER stress, which are hallmarks of pregnancy disorders. Additionally, the dual perfusion model will also serve as a tool to verify if drugs established within the NCCR network can pass through the materno-fetal barrier and therefore reach the fetus.