Chapter Eight - Gametogenesis: A journey from inception to conception

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Abstract

Gametogenesis, the process of forming mature germ cells, is an integral part of both an individual's and a species' health and well-being. This chapter focuses on critical male and female genetic and epigenetic processes underlying normal gamete formation through their differentiation to fertilization. Finally, we explore how knowledge gained from this field has contributed to progress in areas with great clinical promise, such as in vitro gametogenesis.

Section snippets

Germ cell specification and gonadal morphogenesis

Gametes serve as a link between the past, present, and future of a species. Unlike somatic cells, germ cells undergo a series of mitotic and meiotic divisions, followed by a differentiation program giving rise to either sperm or egg. These two mature gametes come together at the process of fertilization to produce the totipotent zygote, from which all somatic lineages/tissue and the next generation of gametes will later arise. This cycle continues indefinitely from one generation to the next,

Germ cell sex determination

As somatic cells commit to testis or ovary lineages, germ cells also undergo sex differentiation in the fetal gonad and become developmentally restricted (Adams & McLaren, 2002). Meiotic entry is generally considered a hallmark of female sex differentiation. In mice, female germ cells begin to enter meiosis at ~ E13.5, and progress through leptotene, zygotene, and pachytene stages, and become arrested at the diplotene stage between E17.5 and P5 (Borum, 1961). In the male gonad ~ E14.5, gonocytes

Oogenesis

In mammalian females, primordial follicles that form during the fetal stage serve as the only source for egg production in adulthood. Oogenesis is comprised of two stages: oocyte differentiation (embryonic) and oocyte development (postpuberty). During oocyte differentiation, PGCs differentiate into primary oocytes, which are further encapsulated by a single layer of pregranulosa cells to form primordial follicles. During oocyte development, primordial follicles develop into mature follicles

Spermatogenesis

The production of sperm is a continuous process throughout an individual's lifespan, which relies on the constant supply of a rare population of cells with long-term renewal potential, called spermatogonial stem cells (SSCs), located along the basement membrane of the seminiferous tubules of the testes. In rodents, these cells are largely described by their clonal arrangement and expression of a variety of heterogeneous molecular markers. Spermatogonial cell proliferation and their ultimate

Epigenetic reprogramming in PGCs, gametes, and early embryos

The epigenome consists of chemical modifications on either histone proteins or DNA. The interplay between the epigenome, signal-transduction pathways, and transcription factors confers gene expression patterns in a cell, which are stably maintained in subsequent mitotic divisions. Unlike somatic cells, the sperm and egg genomes undergo two waves of epigenetic reprogramming. The first wave occurs in the embryo, but the erasure during this phase is incomplete—leaving maternally and paternally

In vitro gametogenesis

Producing mature eggs or sperm using in vitro culture has been a research focus of reproductive biology since the early 1900s (Nagamatsu & Hayashi, 2017). Early studies of in vitro gametogenesis mostly focused on establishing organ culture conditions that produce mature oocytes from immature follicles or mature sperm from testicular tissue (Champy, 1920; Cortvrindt, Smitz, & Van Steirteghem, 1996; Eppig, 1977; Eppig & O'Brien, 1996; Eppig & Schroeder, 1989; Martinovitch, 1937). By using fetal

Conclusion

The production of genetically (and epigenetically) competent gametes is necessary for normal fertilization and early embryonic development. Thus, understanding the underlying processes in vivo will allow us to better recapitulate this process in vitro, and potentially aid in better defining and understanding idiopathic infertility. The research highlighted over the past few decades has not only broadened our knowledge of gamete and embryo development, and related disorders like infertility and

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