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Study of the mechanisms underlying the salutary effects of Heme Oxygenase-1 in implantation, placentation and fetal growth using a mouse model and in vitro approaches. Participation of carbon monoxide in the preparation of the murine uterine microenvironment for pregnancy.

Subject Area Reproductive Medicine, Urology
Gynaecology and Obstetrics
Term from 2015 to 2022
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 277699676
 
Final Report Year 2022

Final Report Abstract

In conclusion, during this project we: a) established a valuable method to follow up pregnancy in vivo and clearly analyze implantation numbers, implantation sizes, fetal growth, placental growth, fetal and placental parameters. Additionally, using Doppler measurements we were able to measure maternal and fetal blood flow. This is a valuable and top-class method to enormously reduce the number of animals used in experiments while maximizing the information obtained within them. b) observed that, contrary to our hypothesis and expectations, Hmox1 partial deficiency did not impact the superovulation yield, nor did influence the fertilization success rate. Additionally, CO exposure during fertilization could not significantly improve the outcome. c) showed that not only maternal, but also paternal HO-1 expression is relevant for pregnancy success in vivo. This could be done using Hmox1 wildtype, heterozygous and knockout female and male mice. We therefore refrained to do IVF and transfer experiments as they were not longer relevant. d) were able to demonstrate the importance of HO-1 expression in human trophoblasts for their attachment to endometrial cells during the process of implantation using a cell line-based approach. We additionally showed that CO was able to restore attachment if HO-1 was knocked-down by siRNA. Thus, HO-1 facilitates attachment by releasing CO. In conclusion, we contributed to the knowledge as how HO-1 and its prominent metabolite CO contribute to fertilization, implantation and pregnancy.

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