Germ Cell Development and Epigenetics

Oocyte (egg) and surrounding cumulus cells. This cell image received a commendation from Light Microscopy Australia in 2019.

Overview

The Germ Cell Development and Epigenetics group aims to improve understanding of epigenetics in reproductive health, germ cells and the effects of epigenetic changes on offspring.

Germ cells form oocytes (eggs) in females and sperm in males which are essential for fertility and the transmission of each parent’s genetic and epigenetic information to offspring. Germ cells develop within the ovaries and testes, which are critical for egg and sperm production, fertility, hormone production and regulating reproductive health.

Epigenetic modifications to the chromatin (DNA plus the histone proteins that package it) provide a long-term ‘directory’ or ‘memory”’of which genes should be switched on or off in each cell, and thereby underpin cell identity and organ function. Conversely, disrupted epigenetic states occur in diseases including cancer, metabolic and behavioural disorders.

Importantly, epigenetic modifications are reversible, allowing gene activity to be changed when necessary. This occurs extensively in cells as they regulate tissue function and is particularly important in germ cells in which epigenetic information is re-set to equip the sperm and oocyte with the appropriate epigenetic information for directing embryonic and post-natal development in the offspring.

However, epigenetic programming is susceptible to alteration by environmental influences such as chemicals, diet and drugs. Significantly, altered epigenetic states can affect ovary and testis function and germline epigenetic information that is transmitted to the next generation and may affect health and development in the offspring. Such changes may contribute to altered reproductive health and developmental origins of health and disease (DoHAD) in a parent’s offspring.

Specifically, the Germ Cell Development and Epigenetics group uses genetic models and pharmacological drugs to disrupt epigenetic modifier function to determine

• The roll of specific epigenetic modifiers in germ cell (egg and sperm) development and function
• The ability of germ cells with altered epigenetic states to direct development in the parent’s offspring
• How epigenetic mechanisms regulate ovarian and testis development and function, and reproductive health.

Our ex-vivo gonad culture, in-vivo mouse genetic and human clinical models are used to examine the function of epigenetics in ovary, testis and germ cell development and germline epigenetic programming to provide insights into the epigenetic basis of reproductive health, germline epigenetic programming and offspring health. Our research aims to further understand human reproductive health and inherited disease, including the potential impacts of novel drugs that target epigenetic processes.

Human health areas: Inherited disorders; Premature Ovarian Insufficiency and Infertility; Ovarian Cancer, Female Reproductive Health