Chapter Eight - Gametogenesis: A journey from inception to conception
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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Cited by (49)
Transgenerational inheritance and its modulation by environmental cues
2023, Current Topics in Developmental BiologyCitation Excerpt :In addition, it has been recently shown that the three-dimensional organization of the chromatin within the nucleus also preserves mPGCs from pervasive transcription, with an augmented chromatin insulation mediated by CTCF (Nagano et al., 2022). At their arrival in the developing somatic gonad, by E11.5, mPGCs are on the onset of gametogenesis, during which sex differentiation and meiosis will occur, ultimately generating the functional gametes: oocytes or spermatozoa (Larose et al., 2019). During this time, mPGCs undergo licensing, a developmental transition regulated by the RNA-binding protein DAZL, that enables the cells to acquire the competence to respond to feminizing or masculinizing cues produced by the fetal ovary or testis (Gill, Hu, Lin, & Page, 2011).
Transgenerational epigenetic impacts of parental infection on offspring health and disease susceptibility
2022, Trends in GeneticsCitation Excerpt :These reset periods restore totipotency in the embryo and prevent many epigenetic aberrations from being inherited [2]. Furthermore, the developing sperm undergoes extensive chromatin remodelling during maturation as shown in Box 1 [27], which has previously led scientists to believe that paternal epigenetic inheritance is unlikely to occur. Contrastingly, these reprogramming and chromatin remodelling periods have been identified as critical periods where environmental insults can cause heritable epigenetic changes [2].
A meiotic switch in lysosome activity supports spermatocyte development in young flies but collapses with age
2022, iScienceCitation Excerpt :We conclude that inhibiting lysosome activity in individual germ-cell clones, starting from the germline stem-cell division, ultimately impedes the formation of a live, meiotic germ cell in male flies. Although gametogenesis has been studied extensively in various experimental animals (Larose et al., 2019), there are still fundamental gaps in our knowledge of the underlying cell biology. For one, the regulation of key organelles, such as lysosomes, is somewhat mysterious.
Sperm histone H3 lysine 4 tri-methylation serves as a metabolic sensor of paternal obesity and is associated with the inheritance of metabolic dysfunction
2022, Molecular MetabolismCitation Excerpt :These findings indicate that paternal obesity alters the sperm epigenome at distinct genes and functional pathways than those differentially expressed in offspring livers; these findings also fit with a developmental origin of adult metabolic dysfunction that could be related to alterations in gene expression in the embryo and placenta. In mammals, spermatogenesis is a highly complex cell differentiation process involving unique testis-specific gene expression programs that are accompanied by dynamic remodeling of the chromatin [92–95]. During this process, most histones are replaced by protamines to facilitate DNA compaction [92].
Distinct sex-dependent effects of maternal preconception nicotine and enrichment on the early development of rat offspring brain and behavior
2022, Neurotoxicology and TeratologyCitation Excerpt :However, the different natures of oogenesis and spermatogenesis may mean that this length of exposure is not ideal for maternal studies. Spermatogenesis is an ongoing process that begins with sexual maturation, whereas females are born with all the oocytes they will ever have (primary oocytes), which periodically mature beginning with sexual maturation (Larose et al., 2019). Therefore, the impact of a preconception experience on the epigenetic signature of germ cells may be fundamentally different between males and females.
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Equal first authors.