Understanding ovarian biology to protect and improve fertility
The Oocytes and Ovaries Research group, led by Professor Suzannah Williams, forms part of our department's Reproductive Medicine & Genetics theme.
Interested in this research?
Oocytes and Ovaries
Why this project is important?
Oocyte quality declines with age, but the mechanisms that regulate this decline are less well understood. There is also still much to learn about the complex mechanisms that regulate follicle selection, development and function, particularly the role of the oocyte.
Primary ovarian insufficiency (POI; previously known as premature ovarian failure, POF) affects 1% of women under the age of 40, yet the cause remains unknown in around 70% of cases. Around 50% of ovaries from women with POF still contain follicles, suggesting that in some cases the ovaries have stopped functioning rather than depleted their supply of follicles.
Understanding ovarian function in health and disease is therefore important for developing new fertility treatments and fertility preservation methods for girls and women.
How the Oocytes and ovaries project can help
The Oocytes and Ovaries group studies ovarian function in health and disease, with the aim of developing new fertility treatments and fertility preservation technologies.
By investigating the mechanisms that regulate oocyte and follicle development, the team aims to better understand areas including ovarian ageing, follicle selection and primary ovarian insufficiency (POI). Using mouse models and in vitroculture systems, researchers can investigate specific biological processes and explore how they affect ovarian and oocyte function.
The research
Unravelling the mechanisms that Regulate Follicle Development
The mechanisms that regulate follicle development are complex and although we know a great deal about the interactions required for successful follicle development, there is still much to be understood about follicle selection and function - particularly regarding the role of the oocyte.
- A mouse model generated by Prof. Williams has been particularly useful in teasing apart the role of the oocyte in follicle development since this model generates oocytes lacking core 1-derived O-glycans and this promotes follicle development leading to an increase in the number of follicles and also ovulation rate. In addition, we have identified a novel role for the oocyte in follicle basal lamina development with follicles containing mutant oocytes having altered basal lamina morphologies, how this affects follicle function is under investigation.
- In addition we also use various in vitro culture systems to investigate follicle culture, notably the reaggregated ovary model, where the ovary is taken apart into single cells and the different populations can be recombined in different ways to answer specific biological questions.
Investigating the aetiology of premature ovarian failure
Premature ovarian failure (POF) is a common condition affecting 1% of women under 40 years of age. However, despite its high prevalence, the majority of the causes for this distressing condition, ~70%, remain unknown.
The common perception is that ovaries of women with POF no longer contain follicles, however this is not the case since around 50% of ovaries still contain follicles, and thus the ovaries have stopped functioning, this is also known as resistant ovary syndrome (ROS).
Prof. Williams generated a mouse model of premature ovarian failure in order to study the aetiology of this disease with the aim of developing treatments.
The effects of ageing on oocyte quality and follicle development
It is well know that oocyte quality declines with age and the defects that occur are well characterised, however the mechanisms that regulate this declining quality are less well understood and is an aspect of ageing we are investigating.
Cumulus Expansion Form and Function
The cumulus mass surrounding the oocyte is required for oocyte maturation and collection of the ovulated egg by the oviduct. Correct expansion requires cumulus cells to secrete extracellular molecules such as hyaluronan, PTX3, TSG-6 which cross-link with the heavy chains (HCs) of serum-derived inter-α-inhibitor proteins resulting in expansion of the cells by mucification.
Furthermore, it was previously understood that the relationships between these molecules was tightly linked and all were required as deficiencies in any one of these led to defective expansion and reduced fertility.
However, recent studies in our group led by Panayiota Ploutarchou have demonstrated that this perception of cumulus expansion is not strictly true. Investigations into cumulus expansion using the C1galt1 mouse model which ovulates eggs with a modified modified cumulus expansion that does not negatively affect fertilisation or fertility led us to explore this concept by investigating the levels of the different molecules in individual cumulus matrixes.
These studies revealed that there is a high degree of flexibility in the levels of the molecules required for cumulus expansion and most surprisingly, considering the perception that the molecules were highly dependent on each other, there was no correlation between the molecules or the activation of the signalling pathways required for expansion.
Useful links
Rhino Fertility Project
Finding new ways of saving the Northern White Rhino by using tissue taken from animal ovaries to produce potentially large numbers of eggs in a laboratory setting.
Postgraduate Study in Reproductive Health
The Nuffield Department of Women’s & Reproductive Health offers a range of postgraduate taught and research programmes in reproductive health, providing opportunities to learn from leading researchers and explore the latest developments across women’s and reproductive health.
Reproductive Medicine & Genetics Theme
The Nuffield Department of Women's and Reproductive Health manages over 30 research groups that fall within either Global Health, Cancer, Maternal & Fetal Health; Big data; and Reproductive Medicine & Genetics.
Key publications
Variation in follicle health and development in cultured cryopreserved ovarian cortical tissue: a study of ovarian tissue from patients undergoing fertility preservation.
Journal article
Walker CA. et al, (2021), Hum Fertil (Camb), 24, 188 - 198
Improved preservation of ovarian tissue morphology that is compatible with antigen detection using a fixative mixture of formalin and acetic acid.
Journal article
Adeniran BV. et al, (2021), Hum Reprod, 36, 1871 - 1890
Oocyte-specific ablation of N- and O-glycans alters cumulus cell signalling and extracellular matrix composition.
Journal article
Lo BKM. et al, (2019), Reprod Fertil Dev, 31, 529 - 537
In vitro and in vivo mouse follicle development in ovaries and reaggregated ovaries.
Journal article
Lo BKM. et al, (2019), Reproduction, 157, 135 - 148
Formation of multiple-oocyte follicles in culture.
Journal article
Christensen AP. et al, (2017), In Vitro Cell Dev Biol Anim, 53, 791 - 797
The research team
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Suzannah Williams
Associate Professor & Senior Research Fellow
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Nilay Kuscu
Postdoctoral Research Assistant
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Emmerson Teas
DPhil Student
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Rabinoor Khurana
MSc by Research Student
How can you help?
You can support the ongoing work of the Ovaries and Oocytes project through donations, collaborations and research support. If you wish to support our work, please contact Professor Williams below.