Identification of human-specific regulatory mechanisms in female germ cell development

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Human female fertility stretches over decades, but all the oocytes (eggs) necessary for this are formed before birth. Therefore at the time of her birth, a woman's ovary contains all the oocytes she will ever have. The number and also the quality of these oocytes then declines and when the supply of oocytes is exhausted at the menopause, women not only reach the end of their fertility, but are at increased risk of other health problems related to bone, cardiovascular and cognitive function. Having sufficient eggs to ensure normal fertility and age at menopause is therefore central to lifelong women's health. The type of cell division called meiosis, which is essential for the manufacture of oocytes that are capable of fertilisation in adult life, is initiated during fetal life and therefore events that occur before birth will determine a woman's fertility and reproductive lifespan. Gene expression is a multi-step process where mRNA, which is made from DNA (itself the genetic blueprint) is used as a template to make proteins. In order to function properly, oocytes need to make proteins at the right time, place and in the correct amount, and this is regulated by RNA binding proteins. Oocytes have specific RNA binding proteins that are critical for their development and these proteins have specific mRNA targets which they recognise and bind to, thereby controlling gene expression. DAZL and BOLL are two RNA binding proteins that are specifically found in oocytes of all mammalian species and we have shown in the human, there is a switch from DAZL to BOLL during the early stages of meiosis. This switch does not happen in mice. Our previous research has revealed some of the mRNA targets that are regulated by DAZL in human fetal oocytes, and in this project we wish to identify the key mRNA targets regulated by BOLL, to find out how BOLL contributes to meiotic progression and follicle formation, thus to overall human oocyte development and setting up a woman's fertility. It is essential to do this in humans because of this switch that seems to be necessary for normal human, but not rodent, oocyte development. This work will shed light on the key steps necessary to make sufficient and good quality eggs that are the basis for women's life-long fertility.