Abstract
Primordial germ cells undergo three significant processes on their path to becoming primary oocytes: the initiation of meiosis, the formation and breakdown of germ cell nests, and the assembly of single oocytes into primordial follicles. However at the onset of meiosis, the germ cell becomes transcriptionally silenced. Consequently translational control of pre-stored mRNAs plays a central role in coordinating gene expression throughout the remainder of oogenesis; RNA binding proteins are key to this regulation. In this review we examine the role of exemplars of such proteins, namely LIN28, DAZL, BOLL and FMRP, and highlight how their roles during germ cell development are critical to oogenesis and the establishment of the primordial follicle pool.
Highlights
The finite nature of human female fertility is underpinned by the formation of a non-renewable reserve of primordial follicles that are assembled from mid-gestation onwards in humans (reviewed in (Findlay et al, 2015))
Establishment of the ovarian reserve begins with the migration of primordial germ cells (PGCs) from the proximal epiblast to the genital ridge; a process already underway in the human embryo at four weeks of development (Witschi, 1948; Mollgard et al, 2010), and which is largely complete by the eighth week of gestation (6 weeks post conception) (De Felici, 2013)
In this review we examine the role of such RNA-binding proteins (RBPs), LIN28, DAZL, BOLL and Fragile X Mental Retardation Protein (FMRP), in initiating and sustaining germ cell development in the human fetal ovary (Fig. 1), and highlight recent findings made by ourselves and others in this regard
Summary
The finite nature of human female fertility is underpinned by the formation of a non-renewable reserve of primordial follicles that are assembled from mid-gestation onwards in humans (reviewed in (Findlay et al, 2015)). Upon arrival at the gonad, and following female sex specification, PGCs undergo three significant, overlapping and possibly interconnected processes on their journey to becoming functional oocytes, namely: the initiation of meiosis, the formation and breakdown of germ cell nests, and the assembly of single oocytes into primordial follicles. It is these follicles which constitute the ovarian reserve for the adult life of women, and the developmental events prior to, and during their foundation, that lay the foundations of developmental competence required to form an oocyte that is capable of fertilisation in adult life
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