Abortion, Habitual; Gestational Trophoblastic Disease; Obstetrics; Placenta; Pregnancy Complications; Pregnancy Outcome; Trophoblasts
- Reproductive Biology Unit
Head: Martin Knöfler
Research Area: biological function, differentiation and development of the human placenta
“Science is the search for truth that is the effort to understand the world.” (L. Pauling)
In placental research, the “truth” of a series of processes that takes place at the fetal-maternal interface, and that is a prerequisite for a successful pregnancy outcome, still needs to be unraveled. In detail, the fetal placenta anchors with its villous tree to the maternal uterine tissue, referred to as decidua. Afterward, precisely controlled differentiation processes give rise to proliferative cell columns, which differentiate into highly invasive extravillous trophoblasts (EVTs) at their distal end. These cells penetrate the decidua and fulfill fundamental functions (e.g., invasion/ remodeling of vessels and glands, secretion of pregnancy-related factors, and interaction with immune cells). Importantly, defective EVT functions are associated with severe pregnancy complications (e.g., recurrent spontaneous abortion [RSA], preeclampsia, and intrauterine growth restriction). Hence, the overall goal is to identify the mechanisms that underlie abnormal placental development and function and to transfer these findings into clinically useful tools to improve pregnancy outcomes.
Currently, my research interests encompass two issues:
1. The interaction of decidual vessels and immune cells in healthy pregnancies vs. idiopathic RSA
2. EVT-derived secretome to identify diagnostic markers for pregnancy complications
Techniques, methods & infrastructure
- Primary cell culture of human trophoblasts, trophoblastic cell lines, villous explant culture model systems, trophoblast organoids
- various biochemical, cell biological and imaging techniques (e.g., immunofluorescence of sections and cells, western blot, RNA interference, semi-quantitative/real-time PCR, ELISA, flow cytometry and laser-captured microdissection)
- Clinical Research
- Moser, G. et al., 2018. Human trophoblast invasion: new and unexpected routes and functions. Histochemistry and Cell Biology, 150(4), pp.361-370. Available at: http://dx.doi.org/10.1007/s00418-018-1699-0.
- Velicky, P. et al., 2018. Pregnancy-associated diamine oxidase originates from extravillous trophoblasts and is decreased in early-onset preeclampsia. Scientific Reports, 8(1). Available at: http://dx.doi.org/10.1038/s41598-018-24652-0.
- Windsperger, K. et al., 2017. Extravillous trophoblast invasion of venous as well as lymphatic vessels is altered in idiopathic, recurrent, spontaneous abortions. Human Reproduction, 32(6), pp.1208-1217. Available at: http://dx.doi.org/10.1093/humrep/dex058.