Reproduction toxicology and childhood cancer

Description

Project leader: Faranak Azarbayjani

Reproductive toxicity: The rates of infertility are growing in the world. In Vitro Fertilization (IVF) is one of the most common treatments, but the success rates of this method are still low. Maternal mRNA (transcriptome) regulates all the early stages of embryonic development and is therefore vital for maternal capacity to support embryonic development and seems to be crucial for embryonic competence for successful pregnancy.

Thus, the aim of this project is to elucidate basic molecular events in early embryonic development by focusing on maternal transcriptome in an IVF-model of porcine conceptus. Additionally, we would like to evaluate the effect of exposure to commonly used prescription drugs on maternal transcriptome.

The porcine IVF system is an attractive model in such studies and permits the controlled addition of test chemicals at biologically relevant concentrations.

We anticipate that studying transcriptome dynamics in these specific and early stages of development will give insights to the important pathways that could determine embryonic competence and ultimately be used as early predictors of successful IVF.

Childhood cancer: Neuroblastoma (NB) is a childhood, neuroendocrine tumor arising in the sympathetic nervous system. The overall NB survival has only been moderately improved despite intensive treatment protocols.

Our earlier preclinical studies have shown that treating the tumors with angiogenesis inhibitors such as Avastin® or Sutent® could halt tumor growth in both subcutaneous and orthotopic models of NB.

The mechanism for anti-tumorigenic effects of these treatments were either inhibition of tumor angiogenesis or “silencing” of the stroma by acting on stromal immune cells such as tumor associated macrophages (TAMs).

We are therefore interested in studying the role of immune cells residing in tumor microenvironment in promoting tumor growth and effects of treatment with angiogenesis inhibitors on these cells.