Follicular Development and Oocyte Growth

Follicular development begins as early as the fourth month of fetal life [1]. At that time, the primordial germ cells (PGCs) have migrated from the yolk sac endoderm to the gonadal ridge, undergoing mitotic divisions. PGCs are called oogonia once they reach the gonads, then the oogonia enter the first meiotic division and become primary oocytes. Somatic cells originating from the primitive gonad surround the oogonia, forming primordial follicles [2]. These primordial follicles constitute the ovarian follicular reserve, which provides a woman with reproductive potential during her entire lifetime. It is a central dogma in reproductive biology that during the life of the individual there cannot be any increase in the number of primary oocytes beyond those originally laid down when the ovary was formed. However, a series of recent studies have challenged this dogma by showing regeneration of oocytes from putative germ cells in bone marrow and peripheral blood [3–5]. Future studies may address whether spontaneous neo-oogenesis takes place in the adult ovary. The follicles develop through primordial, primary, and secondary stages before acquiring an antral cavity. At the antral stage, most follicles undergo atresia. After pubertal onset, maturation of the hypothalamus–pituitary–ovarian (HPO) axis results in pulsatile release of folliclestimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary, so a few of the antral follicles can be rescued by gonadotropins to continue growth and normally one antral follicle can reach the pre-ovulatory stage each month [6, 7]. In a natural menstrual cycle, there is only one follicle will be chosen to ovulate eventually while others going atresia under the accurate regulation of both HPO axis and intra-ovarian regulators, such as growth factors, cytokines, and gonadal steroids. But more recent results document that multiple follicle waves may exist during the human menstrual cycle, which has challenged the traditional notion [8]. During ovarian follicle development, oocytes also grow and differentiate, and a complex cytoplasmic organization is required [9]. The growth phase of the oocyte allows development of the zona pellucida and production of mRNA and proteins required for subsequent fertilization and early embryonic development. These factors must be stored within the oocyte, as resumption of meiosis results in transcriptional silencing [10]. Oocyte developmental competence, defined as the ability of the oocyte to resume and complete meiosis, and support pre-implantation embryonic development after fertilization, is acquired gradually during folliculogenesis. H. Li Medical School, Tongji University, No 1239, Siping Road, Shanghai 200092, China e-mail: [email protected]