Folliculogenesis describes the process of activating an oocyte-containing primordial follicle from the ovarian reserve, and its development to the mature ovulatory stage. This process is highly complex and is controlled by extra- and intra-ovarian signalling events. Oocyte competence and capacity for fertilisation to support a viable pregnancy is acquired during folliculogenesis. Cancer, and cancer-based therapies can negatively affect this process, compromising fertility. Currently, preservation of fertility in these patients remains limited to surrogacy, oocyte freezing, oocyte donation or in vitro maturation (IVM). Recent reports of stem cells being used to produce fully competent oocytes, and subsequently healthy offspring in mice, has opened up a novel avenue for fertility preservation. However, translating these findings into human health first relies on enhancing our understanding of follicle growth, and mimicking its intricacies in vitro. Indeed, the future of oocytes from stem cells in humans comes with many possibilities, but currently faces several technical and ethical obstacles.

Overview of folliculogenesis and building a competent oocyte

The ovarian follicle containing an oocyte surrounded by somatic cells is the niche for the female germline which must be nourished and protected from sustained damage. The germ cells that eventually form follicles are first identified at 4 weeks gestation among stem cells in the embryonic epiblast. After migration to the gonadal ridge and proliferation, they enter meiosis and form nests surrounded by pre-granulosa cells. The nests breakdown between 25 and 40 weeks gestation to form primordial follicles, each of which contains an oocyte arrested in prophase of the meiotic cell cycle, surrounded by a single layer of squamous or flattened pre-granulosa cells. This process called oogenesis occurs over 150 and 250 days in the fetal ovary (Figure 1) (1, 2). At birth, the human female has approximately 300,000 primordial follicles (range 35,000-2.5 million), defined as the ovarian reserve (1, 3).This reserve is not replenished after birth under normal physiological circumstances. The size of the ovarian reserve declines with age until <1000 primordial follicles are present at the time of menopause (3, 4). The length of the fertile period from puberty to menopause is determined by (a) the rate of death of primordial follicles before being selected to activate, (b) their rate of activation, and (c) the size of the ovarian reserve at birth (1, 5). It follows that genetic or environmental factors such as chemotherapeutic agents or radiation that reduce the size of the ovarian reserve will shorten or even eliminate the fertile period.