Project Details
Projekt
The role of reactive oxygen species (ROS) in the signaling of FSH and ovarian factors
Subject Area
Reproductive Medicine, Urology
Endocrinology, Diabetology, Metabolism
Endocrinology, Diabetology, Metabolism
Term
from 2014 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 262625742
While noxious actions of reactive oxygen species (ROS) are implicated in human ovarian pathology, their roles in ovarian physiology are surprisingly unknown. The recently documented essential involvement of ROS in ovulatory events strongly supports such a role in rodents. Our studies in IVF (in vitro fertilization)-derived human granulosa cells (GCs) showed that ROS are generated, when ovarian growth factors (e.g. EGF) or catecholamines act on human GCs. In course of these studies we made the observation that follicle stimulating hormone (FSH), i.e. the master hormone governing follicular development, also resulted in the generation of ROS in human GCs and the ROS involved was identified as H2O2. Given the fundamental importance and widespread use of FSH in reproductive medicine, we plan to explore this unknown part of FSH action with a focus on the human situation. Our preliminary results let us suspect involvement of the ROS generating enzymes of the NOX/DUOX family and/or of EGF receptor transactivation in the novel aspect of FSH action. Hence we will examine, how FSH leads to the generation of H2O2, how H2O2 acts as an intracellular signaling factor in GCs and whether it may also be a short-range extracellular signaling molecule. To this end a series of descriptive and functional studies are planned. Localization studies will trace NOX/DUOX-forms/EGF receptors in ovarian follicles during follicular development. Cellular and molecular studies will examine the signaling pathway of FSH that leads to H2O2 generation and the consequences of this ROS on GCs. Possible interactions between the ROS augmenting activities of FSH with other ovarian factors will be studied experimentally and by a computational analysis. We expect that our exploratory project will yield results, which may allow a better understanding of the actions of a crucial hormone in female reproduction. We believe that our results are of possible clinical importance.
DFG Programme
Research Grants
