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. We are investigating the mechanisms that control egg supply and health during ovarian development and throughout reproductive life.
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.
Our laboratory, together with colleagues from the Walter & Eliza Hall Institute and the University of Edinburgh, is investigating the genes and proteins involved in determining whether a germ cell will live or die. We have discovered that a family of cell death proteins, known as BH3-only proteins, play critical roles in the initiation of germ cell death and act to limit the size of the germ cell pool before birth. We are now determining if it is possible to prevent germ cell death and increase the number of eggs available in adult life to prolong fertility and delay menopause by inhibiting or eliminating BH3-only proteins.
- Monash University, Melbourne
- Walter & Eliza Hall Institute, Melbourne