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Defining the role of FSH in oocyte development

Follicle-stimulating hormone (FSH) is administered to patients undergoing assisted reproduction. Although it plays a crucial role during growth of the ovarian follicle, which encloses the oocyte, we do not know whether FSH is also required for development of the oocyte itself. Understanding its role is crucial for determining the appropriate level of hormonal stimulation and for optimizing culture systems for growing follicles and their oocytes in vitro. To do so, we study mice that cannot produce FSH. We have found that the oocytes of these Fshb-/- mice are morphologically normal. However, the granulosa cells, which surround the oocyte and provide factors that are essential for its development, become prematurely detached from the oocytes. Following fertilization, the embryos derived from Fshb-/- oocytes cannot develop normally. Based on these results, we hypothesize that FSH is required to maintain gap junctional communication between the oocyte and its surrounding granulosa cells and that FSH-dependent communication is required for the oocyte to acquire the ability to develop as an embryo.

1. Define the role of FSH in maintaining gap junctional communication between the oocyte and granulosa cells.
2. Test whether gap junctional communication is required for oocytes to become able to develop as embryos.
3. Test whether inhibiting apoptosis can rescue the ability of Fshb-/- oocytes to develop as embryos and thus substitute for FSH.

We will identify the stage of development when oocyte-granulosa cell contact and gap junctional communication are lost in Fshb-/- mice and test whether adding FSH increases communication when oocyte-granulosa complexes are grown in vitro. We will test whether impairing communication reduces the ability of oocytes to develop as embryos. We will test whether blocking apoptosis, either genetically or pharmacologically, maintains communication and allows Fshb-/- oocytes that to give rise to healthy embryos. 

Funding: Canadian Institutes of Health Research

Principal investigator: Hugh Clarke profile