Basic and Clinical Science Research Programs

Ovarian and Follicular Function

Ovarian research examines the basic physiology and biology of the ovary to improve clinical outcomes, particularly in polycystic ovary syndrome. Research also investigates the cellular biology of the ovarian follicle. Current research programs are directed at -

• The role of leukocytes and in particular macrophages in the ovary and the way that they interact with the theca, granulosa layers and the oocyte.
• The mechanisms whereby polycystic ovary syndrome is expressed and the contribution of androgen receptor action and polymorphisms.
• The interrelationships between diet, nutrition and ovarian function as evidenced by polycystic ovary syndrome.
• The study of the extracellular matrix, including the follicular basal lamina and the genesis of the epithelial membrana granulosa

Key Contacts:
Prof Robert Norman
Prof Ray Rodgers
Dr Darryl Russell
Dr Rebecca Robker

Oocyte and Early Embryo Development

This Program investigates the important step of oocyte maturation, fertilisation and early embryo development. A significant importance of this resarch is its clinical and veterinary application, especially in assisted reproductive technologies, as well as understanding basic mechanisms involved in development. Current research programs are directed at:

• The influence of the external microevironment surrounding oocytes and early embryos on embryonic programming and fetal development.
• Maternal factors programming oocyte and early embryo development leading to altered fetal and placental development.
• The molecular and biochemical signals regulating early development.
• Novel systems for the automation of embryo production.
• Diagnostic evaluation of sperm, oocytes and early embryos.
• Oocyte and embryo freezing and storage.
• Research on oocyte secreted factrors and GDF-9/9B, their role, production and regulation.
• Studies on the regulation of oocyte maturation and cumulus cell function by paracrine/gap junctional signalling between the 2 cell types, including exchange of small regulatory molecules such as cAMP. These projects include true IVM (ie effects on embryo developmetnal potential).
• Work continues using the marmoset primate model to investigate characterisation of the role of FSH in reproductive cycles.
• In vitro maturation: physiological and molecular mechanisms of oocyte cytoplasmic maturation in animal models and development of methods for clinical application in assisted reproductive technology.
• Investigations of interactions between hormones (steroids, gonadotrophins) and paracrine growth factors in follicle regulation: in vitro studies with pig and human follicle cell models.
• Role of seminal components in regulation of follicle and corpus luteum development and function: in vivo studies with mouse and pig models
• Enhancement of embryo development and survival by immune modulating molecules: role in increased fecundity in pigs

Key Contacts:
A/Prof Jeremy Thompson
A/Prof Bill Breed
Dr Robert Gilchrist
Dr Michelle Lane
Dr David Mottershead

Uterine Biology

Key Contacts:
Prof Sarah Robertson

Embryo Implantation and Placental Development

Impaired placentral trophoblast invasion of the endometrium has been implicated in a variety of pregnancy complications including implantation failure, recurrent miscarriage, intrauterine growth restriction, pre-term birth and preeclampsia. Together these complications afflict about one third of couples wishing to achieve pregnancy. These may result from deficient endometrial differentiation, deficient pro-invasive factors in trophoblast or an excess of anti-invasive factors in the endometrium or a combination of factors.

We are particularly interested in the molecular mechanisms that control differentiation of the endometrium to create the implantation window and accommodate an invading embryo, placental trophoblast invasion, differentiation and function. This research focuses on the interactions between a variety of growth factors and utilises in vitro and in vivo methods.

Endometriosis is a condition where the lining of the womb grows at sites in the pelvis causing period pain and subfertility for 6-10% of reproductive aged women.  Sufferers of endometriosis require surgery to obtain a diagnosis and then often require repetitive and chronic treatment for this condition.  The aim of the research group is to improve the understanding of the pathophysiology of endometriosis in order to develop better diagnostic and therapeutic tools for this condition.  To explore endometrisois further the research team utilises several in vivo models plus sophisticated molecular and cellular laboratory techniques.

Current research programs are directed at:

• The role of cytokines and immune cells in preparing endometrial receptivity and regulating placental development.
• The role of male seminal factors in conditioning the female reproductive tract for pregnancy.
• The effect of specific growth factors on implantation.
• The interaction between the hormone relaxin and other factors to induce decidualization and differentiation of the endometrium.
• Maternal insulin-like growth factors (IGFs): impact on trophoblast invasion, placental function and fetal growth and survival.
• Developing diagnostic tests to predict risk of pregnancy complications.
• Epigenetic change following perturbations of early pregnancy
• Hormonal control of the myometrium

Key Contacts:
Prof Claire Roberts
Prof Sarah Robertson
Dr Louise Hull
A/Prof Wendy Ingman
Prof Gus Dekker
A/Prof Frank Grutzner
A/Prof Bill Breed
Prof Stefan Heindleder

Male Reproduction

Key Contacts:
Prof Sarah Robertson
A/Prof Bill Breed
Dr Michelle Lane

Reproductive Immunology

The reproductive process is a test of the natural immune system of the female, in both the acceptance of foreign-to-the-body sperm and the implantation of the embryo. It is now recognised that much of the "unexplained infertility" and early embryo loss is a result of immunological rejection and understanding of how the body copes with these challenges will help improve reproductive health and outcomes. Current research programs are directed at -

• Immunology of the female immune response to embryo implantation
• The role of semen in maternal immune tolerance for pregnancy
• Cytokine regulation of early embryo development
• Cytokines and leukocytes in ovarian function
• Novel therapeutics for infertility and recurrent miscarriage
• Improved methods for IVF and human embryo culture

Key Contacts:
Prof Sarah Robertson
A/Prof Wendy Ingman
Dr Rebecca Robker
Dr Louise Hull

Reproductive Biotechnology

This research group has an international reputation in the general areas of reproductive biology and the development of associated technologies such as embryo culture and freezing.

Key Contacts:
A/Prof Jeremy Thompson
Dr Rob Gilchrist

Nutrition, Environment and Reproduction

The Centre's close collaboration with large clinical operations provides an excellent resource for epidemiological studies. Current research programs are directed at -

• Lifestyle and treatment factors that impact on fertility and success from Assisted Reproductive Technology (ART). The projects in this area include the Australian Study of Single Embryo Transfer (ASSET) and studies on obesity, smoking and age.
• Fetal programming of the reproductive axis, and the effects of maternal diet in pregnancy on fetal growth and postnatal development.
• The discovery of the suite of clock gene transcription factors and the recognition that they are rhythmically expressed in a wide range of tissues and organs has led to a broadening of research on the potential roles of circadian rhythms in health and disease. We are actively working in several areas ranging from the control of SCN function to the consequences of rhythm disruption on systems.

Key Contacts:
Prof Robert Norman
A/Prof David Kennaway
Prof Claire Roberts
Dr Rebecca Robker
Prof Gus Dekker
A/Prof Leonie Heilbronn

Early Life Programming of Fetal Development and Adult Health

This research focuses on the peri-conceptual and peri-implantation periods and how pertubations and stress at this time influence later fetal and placental development.

This knowledge is being utilised in the design and testing of interventions to prevent or ameliorate the perinatal factors leading to later disease or their adverse consequences:

• What controls fetal growth and functional development, specifically, the roles of the mother, father and placenta.
• What are the initiating events in utero and the mediating mechanisms involved, whereby the early life environment influences our later development and function after birth. 

Current Projects:

• Maternal insulin-like growth factors (IGFs): impact on placental function and fetal growth and survival.
• Paternal seminal fluid signalling factors and impact on embryo programming.
• Peri-conceptual inflammatory stress and impact on fetal development and post-natal outcomes
• How does infection in utero lead to adverse impact on fetal brain development and incidence of cerebral palsy?
• What are the epigenetic pathways through which embryo development is programmed?

Key Contacts: 
A/Prof Jeremy Thompson
Prof Claire Roberts
Prof Sarah Robertson
Prof Alastair MacLennan
Prof Stefan Heindleder

Menopause Research

This multidisciplinary group is based in the Discipline of Obstetrics and Gynaecology at the Adelaide Women's & Children's Hospital. It conducts epidemiological studies, large clinical trials and educational programmes on the menopause and postmenopausal women's health.

Professor MacLennan is Editor-in-Chief of CLIMACTERIC, The Journal of the International Menopause Society and is a Past President of the Australian Menopause Society.

Recent and Current Projects include:

• Epidemiological studies on pelvic floor dysfunction, alternative therapies and hormone therapy use, quality of life in collaboration with the Department of Health. Population Research and Outcome Studies Unit using the S.A Health Omnibus Survey.
• Cochrane Collaboration systematic review on HRT and vasomotor symptoms.
• The Women's International Study of Long Duration Oestrogen after Menopause (WISDOM).
• Research into Memory, Brain function and Oestrogen Replacement (REMEMBER study) and genetic sub study.
• Tibilone after breast cancer four year study (LIBERATE).
• Long-term Intervention on Fractures with Tibilone Trial (LIFT).
• Phase I, II and III studies on new treatments for menopause and osteoporosis.

Key Contacts:
Prof Alastair Maclennan

Infectious Diseases of the Reproductive and and Gestational Tissues

Key Contacts:
Prof Sarah Robertson

Cancers of the Reproductive System

Key Contacts:
Dr Carmela Ricciardelli
A/Prof Martin Oehler

Breast Biology and Cancer

Breast cancer is the most prevalent type of cancer among women, with approximately 13,000 new cases diagnosed each year in Australia. The aim of our research is to understand the cellular and molecular mechanisms that underpin this high incidence of breast cancer. We study how key risk factors, including menstrual cycling and breast density, lead to increased susceptibility of the mammary gland to cancer, with specific focus on how these risk factors affect the ability of the immune system to protect this unique tissue against carcinogens and other cancer initiating factors. The overarching objective of this research is to provide therapies that reduce a woman's lifetime risk of developing breast cancer.

In addition to studies on breast cancer susceptibility, we also conduct mastitis research. Mastitis is a common inflammatory disease in lactating women that causes pain, fever, low milk supply and leads many to cease breastfeeding. This research explores the cellular mechanisms that lead to inflammation, and investigates potential therapies to quickly and effectively stop the symptoms of mastitis.

Current research programs are directed at:

• The role of transforming growth factor beta in regulating macrophages in the mammary gland
• Understanding the relationship between breast density and cancer risk
• Cell death pathways and the immune response to menstrual cycle-associated mammary gland regression
• The role of complement in breast cancer susceptibility
• Macrophages in the human breast
• Inflammation in mastitis

Key Contacts:
A/Prof Wendy Ingman
Prof Sarah Robertson
Dr Carmela Ricciardelli
Dr Darryl Russell