| dc.description.abstract | Cancer patients may have to undergo specific chemotherapeutic treatments which can damage their reproductive organs,
leading to infertility. For such patients, it may be beneficial to remove parts of their gonads and freeze them in order to
reimplant them later after the cancer therapy has ended. For example, women can have their ovaries frozen, or oocytes can
be extracted from the ovaries and then frozen and stored to be used later with IVF. This is problematic in young female cancer
patients whose ovaries have not yet undergone puberty because their ovaries do not produce ovulatory follicles yet and there
are no mature, competent oocytes to vitrify. Recently, advancements have been made in the in vitro follicle culture of human
oocytes. This is the process where immature follicles are cultured in special media in the presence of specific hormones outside
of the body, eventually allowing the development of a mature, fertile oocyte from an immature follicle after IVM of the antral
follicle. This has already been well described in mice, where fertile offspring have been produced from oocytes generated
Part A – Applicant
TEMPLATE APPLICATON FORM (based on NWO Open Competition Domain Science – KLEIN-1)
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from immature follicles and even from mouse embryonic stem cells. However, the process is difficult to recapitulate in vitro
with human oocytes.
Combining the currently available knowledge, we will develop and refine a protocol to first culture primordial follicles which
are present in pediatric ovaries, and then mature the oocytes in vitro to a state that resembles the oocytes found in vivo
following ovulation. For this purpose, we will be working with frozen material obtained from young female cancer patients.
We will use hormones to stimulate the primordial follicles to grow, after which we will apply pressure to obtain the oocyte
and its surrounding cells from the cultured follicle. We will then culture the oocyte in a special medium together with different
combinations of hormones to evaluate which combination works the best. Alternatively, we will isolate the hormone
producing cells from adult human ovaria and culture them together with primordial follicles. This will simulate the in vivo
environment of adult human ovaries, thereby stimulating the primordial follicles obtained from the pediatric patients to grow
and become ovulatory.
The information obtained will have paved the way for fertility preservation of female pediatric cancer survivors, which is a
currently unmet medical need. Our research will also significantly contribute to this research field, enhancing our
understanding of the way that immature human oocytes develop into fertile reproductive cells. This can in turn lead to further
advances, enabling us to provide novel fertility therapies for infertile persons. | |
