Hutt Lab research
About Associate Professor Karla Hutt
Associate Professor Karla Hutt obtained her PhD from the Australian National University in 2006, where her studies focussed on the establishment and maintenance of the oocyte pool during ovarian development. She then undertook her postdoctoral studies at the University of Kansas Medical Center (USA), where she investigated the impact of environmental toxicants on oocyte and embryo quality. In 2008 she was awarded and NHMRC Early Career Fellowship and returned to Australia and to join Professor Jock Findlay's laboratory at Prince Henrys Institute (now the Hudson Institute of Medical Research). She was subsequently awarded an NHMRC Career Development Fellow (Level 1) to continue her studies. In 2015 she relocated to Monash University, where she now leads the Ovarian Biology Laboratory and is the BDI Outstanding Women in Science Fellow. Her group investigates the factors responsible for determining oocyte number and quality, with the aim of i) improving women’s health and fertility during normal reproductive life and maternal ageing and ii) developing new therapeutic strategies to protect female fertility during anti-cancer therapy and infection.
1. Uncovering the molecular mechanisms that determine the length of the female fertile lifespan.
2. Characterising ovarian damage caused by cancer treatments.
3. Characterising damage to the uterus caused by cancer treatments.
4. Exploring the importance of DNA repair for the maintenance of oocyte number and quality.
5. Determining if Chlamydia infects the ovary and inflicts permanent damage.
Visit Associate Professor Hutt's Monash research profile to see a full listing of current projects.
Egg supply, the fertile lifespan, and age at menopause
Women are born with a limited supply of eggs (oocytes) in their ovaries and are unable to make new eggs after birth. Because of this, the number and health of eggs established within the ovary early in life influence the length of time for which a female will be fertile, her age at menopause, and the health of her offspring. A striking characteristic of normal ovarian development is the extensive, but unexplained, death of the embryonic precursors of eggs (germ cells), leaving a relatively small number of eggs stored in the ovary at birth to sustain fertility and ovarian function throughout life. Why are such a large number of germ cells generated during embryonic development then destroyed? Are these destroyed germ cells eliminated because they are of low quality? What are the genes and proteins that regulate germ cell death? Answering these questions and understanding the mechanisms that determine how many eggs are established and maintained in the ovary is essential, as abnormal regulation of death pathways leading to reduced egg number may compromise female fertility and result in pre-mature menopause. Our work is therefore highly relevant to female fertility and health, as premature menopause not only reduces a woman's chance of having children, but also puts her at early risk of post-menopausal problems such as osteoporosis and heart disease.
Fertility preservation in female cancer patients
Irreversible damage to the ovary is a devastating side effect of many anti-cancer treatments, often leaving cancer survivors unable to have their own children and facing premature menopause. In particular, these treatments can damage the DNA of eggs and induce their death, leading to premature ovarian failure and infertility. Currently, no options exist to protect the ovary from damage and preserve fertility of young women being treated for cancer. Using gene targeted mouse models, our lab is investigating the specific mechanisms by which irradiation and chemotherapy damage the ovary, with the long-term goal of developing new strategies to protect the ovary and preserve fertility through the inhibition of egg death. We are also investigating the hypothesis that cancer treatments damage the uterus and impair the ability to carry a healthy pregnancy.
Exploring the DNA repair capacity of oocytes
Female fertility and offspring health are critically dependent on the maintenance of an adequate supply of high quality oocytes. Little is known about the DNA repair capacity of oocytes and the contribution of DNA repair to oocyte quality has not been investigated. We have shown that under conditions in which apoptosis is inhibited, lesions induced by γ-irradiation are resolved in oocytes within 5 days. Remarkably, these oocytes produced healthy offspring, despite having sustained high levels of DNA damage. These exciting data strongly suggest that oocytes are in fact capable of efficient DNA repair and that DNA repair is an important mechanism for ensuring female fertility as well as the transmission of high quality genetic material to subsequent generations. Our lab is now characterizing the DNA repair response of primordial follicle oocytes, and determining if DNA repair can restore oocyte quality following DNA damage. We are also investigating the possibility that oocytes exhibit altered DNA repair responses with increasing age in humans and mice. Understanding the repair capacity of oocytes has important implications for the 1 in 5 Australian women who delay child bearing until later in life (>35 yr) when oocyte quality is greatly reduced, for understanding the origin of genetic disorders, and for the design of new therapies to inhibit oocyte death and preserve fertility during anti-cancer treatments.
Chlamydia infection in the ovary
Chlamydia trachomatis is the most prevalent sexually transmitted bacterial pathogen worldwide, with over 113 million new cases of infection detected annually and is the most common cause of infertility in women. Chlamydia causes severe damage to the reproductive tracts of infected women and poses a substantial threat to their health, fertility and the future well-being of their offspring. While it is well established that occlusion of the Fallopian tubes causes infertility and ectopic pregnancy in Chlamydia infected women, data suggest that infertility arising from chlamydial infection is not solely the consequence of Fallopian tube scarring and imply that additional mechanisms exist by which female fertility is compromised. Using mouse models of Chlamydia infection, we are investigating the hypothesis that Chlamydia penetrates and damages the ovary and are evaluating the association between prior Chlamydia infection and diminished ovarian reserves, disrupted ovarian function and/or infertility in women.
We use a variety of techniques, including qRT-PCR, Western blotting, stereology, immunofluorescence, in situ hybridisation, 3D confocal imaging and ELISA. We also have expertise in the design of long term fertility trials in mice, and the analyses of offspring health.
Mouse model of Chlamydia infection
Mouse models of ovarian ageing
Mouse models of DNA damage
Mouse models of apoptosis and DNA repair deficiency
We collaborate with many scientists and research organisations around the world. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).
Student research projects
The Hutt Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short term research opportunities available.
Please visit Supervisor Connect to explore the projects currently available in our Lab.