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Seminars in Cell & Developmental Biology Sep 2015Meiosis is one of the defining events in gametogenesis. Male and female germ cells both undergo one round of meiotic cell division during their development in order to... (Review)
Review
Meiosis is one of the defining events in gametogenesis. Male and female germ cells both undergo one round of meiotic cell division during their development in order to reduce the ploidy of the gametes, and thereby maintain the ploidy of the species after fertilisation. However, there are some aspects of meiosis in the female germline, such as the prolonged arrest in dictyate, that appear to predispose oocytes to missegregate their chromosomes and transmit aneuploidies to the next generation. These maternally-derived aneuploidies are particularly problematic in humans where they are major contributors to miscarriage, age-related infertility, and the high incidence of Down's syndrome in human conceptions. This review will discuss how events that occur in foetal oocyte development and during the oocytes' prolonged dictyate arrest can influence meiotic chromosome segregation and the incidence of aneuploidy in adult oocytes.
Topics: Animals; Chromosome Segregation; Crossing Over, Genetic; Female; Humans; Meiosis; Oocytes; Oogenesis; Recombination, Genetic; Trisomy
PubMed: 26454098
DOI: 10.1016/j.semcdb.2015.10.005 -
Current Topics in Developmental Biology 2019Gametogenesis, 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... (Review)
Review
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.
Topics: Animals; Cell Differentiation; Embryonic Stem Cells; Female; Fertilization; Gametogenesis; Gene Expression Regulation, Developmental; Germ Cells; Humans; Male
PubMed: 30797511
DOI: 10.1016/bs.ctdb.2018.12.006 -
Cell Stem Cell Feb 2020The human testis undergoes dramatic developmental and structural changes during puberty, including proliferation and maturation of somatic niche cells, and the onset of...
The human testis undergoes dramatic developmental and structural changes during puberty, including proliferation and maturation of somatic niche cells, and the onset of spermatogenesis. To characterize this understudied process, we profiled and analyzed single-cell transcriptomes of ∼10,000 testicular cells from four boys spanning puberty and compared them to those of infants and adults. During puberty, undifferentiated spermatogonia sequentially expand and differentiate prior to the initiation of gametogenesis. Notably, we identify a common pre-pubertal progenitor for Leydig and myoid cells and delineate candidate factors controlling pubertal differentiation. Furthermore, pre-pubertal Sertoli cells exhibit two distinct transcriptional states differing in metabolic profiles before converging to an alternative single mature population during puberty. Roles for testosterone in Sertoli cell maturation, antimicrobial peptide secretion, and spermatogonial differentiation are further highlighted through single-cell analysis of testosterone-suppressed transfemale testes. Taken together, our transcriptional atlas of the developing human testis provides multiple insights into developmental changes and key factors accompanying male puberty.
Topics: Adult; Humans; Infant; Male; Puberty; Sertoli Cells; Spermatogenesis; Spermatogonia; Testis
PubMed: 31928944
DOI: 10.1016/j.stem.2019.12.005 -
Cell Research Sep 2018A systematic interrogation of male germ cells is key to complete understanding of molecular mechanisms governing spermatogenesis and the development of new strategies...
A systematic interrogation of male germ cells is key to complete understanding of molecular mechanisms governing spermatogenesis and the development of new strategies for infertility therapies and male contraception. Here we develop an approach to purify all types of homogeneous spermatogenic cells by combining transgenic labeling and synchronization of the cycle of the seminiferous epithelium, and subsequent single-cell RNA-sequencing. We reveal extensive and previously uncharacterized dynamic processes and molecular signatures in gene expression, as well as specific patterns of alternative splicing, and novel regulators for specific stages of male germ cell development. Our transcriptomics analyses led us to discover discriminative markers for isolating round spermatids at specific stages, and different embryo developmental potentials between early and late stage spermatids, providing evidence that maturation of round spermatids impacts on embryo development. This work provides valuable insights into mammalian spermatogenesis, and a comprehensive resource for future studies towards the complete elucidation of gametogenesis.
Topics: Animals; Male; Mice; Mice, Inbred Strains; Sequence Analysis, RNA; Single-Cell Analysis; Spermatogenesis
PubMed: 30061742
DOI: 10.1038/s41422-018-0074-y -
Human Reproduction Update 2016Extracellular vesicles (EVs) are membrane-bound vesicles, found in biofluids, that carry and transfer regulatory molecules, such as microRNAs (miRNAs) and proteins, and... (Review)
Review
BACKGROUND
Extracellular vesicles (EVs) are membrane-bound vesicles, found in biofluids, that carry and transfer regulatory molecules, such as microRNAs (miRNAs) and proteins, and may mediate intercellular communication between cells and tissues. EVs have been isolated from a wide variety of biofluids, including plasma, urine, and, relevant to this review, seminal, follicular and uterine luminal fluid. We conducted a systematic search of the literature to review and present the currently available evidence on the possible roles of EVs in follicular growth, resumption of oocyte development and maturation (meiosis), sperm maturation, fertilization and embryo implantation.
METHODS
MEDLINE, Embase and Web of Science databases were searched using keywords pertaining to EVs, including 'extracellular vesicles', 'microvesicles', 'microparticles' and 'exosomes', combined with a range of terms associated with the period of development between fertilization and implantation, including 'oocyte', 'sperm', 'semen', 'fertilization', 'implantation', 'embryo', 'follicular fluid', 'epididymal fluid' and 'seminal fluid'. Relevant research articles published in English (both animal and human studies) were reviewed with no restrictions on publication date (i.e. from earliest database dates to July 2015). References from these articles were used to obtain additional articles.
RESULTS
A total of 1556 records were retrieved from the three databases. After removing duplicates and irrelevant titles, we reviewed the abstracts of 201 articles, which included 92 relevant articles. Both animal and human studies unequivocally identified various types of EVs in seminal, follicular and ULFs. Several studies provided evidence for the roles of EVs in these biofluids. In men, EVs in seminal fluid were linked with post-testicular sperm maturation, including sperm motility acquisition and reduction of oxidative stress. In women, EVs in follicular fluid were shown to contain miRNAs with potential roles in follicular growth, resumption of oocyte meiosis, steroidogenesis and prevention of polyspermy after fertilization. EVs were also detected in the media of cultured embryos, suggesting that EVs released from embryos and the uterus may mediate embryo-endometrium cross-talk during implantation. It is important to note that many of the biologically plausible functions of EVs in reproduction discussed in the current literature have not yet been substantiated by conclusive experimental evidence.
CONCLUSIONS
A detailed understanding of the contributions of EVs in the series of events from gametogenesis to fertilization and then on to implantation, in both normal and pathological cases, may enable the development of valuable tools to advance reproductive health. Because of the early stage of the field, it is unsurprising that the current literature includes not only growing experimental evidence, but also as-yet unproven hypotheses pertaining to the roles of EVs in key reproductive processes. In this review, we present a comprehensive survey of the rapidly expanding literature on this subject, highlighting both relevant findings and gaps in knowledge.
Topics: Animals; Cell Communication; Embryo Implantation; Extracellular Vesicles; Female; Fertilization; Humans; Male; Oocytes; Oogenesis; Pregnancy; Semen; Spermatogenesis
PubMed: 26663221
DOI: 10.1093/humupd/dmv055 -
Nature Reviews. Genetics Mar 2010Cytosine DNA methylation is a stable epigenetic mark that is crucial for diverse biological processes, including gene and transposon silencing, imprinting and X... (Review)
Review
Cytosine DNA methylation is a stable epigenetic mark that is crucial for diverse biological processes, including gene and transposon silencing, imprinting and X chromosome inactivation. Recent findings in plants and animals have greatly increased our understanding of the pathways used to accurately target, maintain and modify patterns of DNA methylation and have revealed unanticipated mechanistic similarities between these organisms. Key roles have emerged for small RNAs, proteins with domains that bind methylated DNA and DNA glycosylases in these processes. Drawing on insights from both plants and animals should deepen our understanding of the regulation and biological significance of DNA methylation.
Topics: Animals; CpG Islands; DNA Methylation; DNA, Plant; Epigenesis, Genetic; Gametogenesis; Histones; Models, Genetic; Plants; RNA, Small Interfering
PubMed: 20142834
DOI: 10.1038/nrg2719 -
Cell Stem Cell Dec 2021Mammalian male germ-cell development consists of three distinct phases: primordial germ cell (PGC) development, male germ-cell specification for spermatogonium...
Mammalian male germ-cell development consists of three distinct phases: primordial germ cell (PGC) development, male germ-cell specification for spermatogonium development, and ensuing spermatogenesis. Here, we show an in vitro reconstitution of whole male germ-cell development by pluripotent stem cells (PSCs). Mouse embryonic stem cells (mESCs) are induced into PGC-like cells (mPGCLCs), which are expanded for epigenetic reprogramming. In reconstituted testes under an optimized condition, such mPGCLCs differentiate into spermatogonium-like cells with proper developmental transitions, gene expression, and cell-cycle dynamics and are expanded robustly as germline stem cell-like cells (GSCLCs) with an appropriate androgenetic epigenome. Importantly, GSCLCs show vigorous spermatogenesis, not only upon transplantation into testes in vivo but also under an in vitro culture of testis transplants, and the resultant spermatids contribute to fertile offspring. By uniting faithful recapitulations of the three phases of male germ-cell development, our study creates a paradigm for the in vitro male gametogenesis by PSCs.
Topics: Animals; Cell Differentiation; Epigenomics; Germ Cells; Male; Mice; Pluripotent Stem Cells; Spermatogenesis; Spermatogonia
PubMed: 34496297
DOI: 10.1016/j.stem.2021.08.005 -
Reproduction (Cambridge, England) Aug 2010Homeobox genes encode transcription factors that have crucial roles in embryogenesis. A recently discovered set of homeobox genes--the Rhox genes--are expressed during... (Review)
Review
Homeobox genes encode transcription factors that have crucial roles in embryogenesis. A recently discovered set of homeobox genes--the Rhox genes--are expressed during both embryogenesis and in adult reproductive tissues. The 33 known mouse Rhox genes are clustered together in a single region on the X chromosome, while likely descendents of the primodial Rhox cluster, Arx and Esx1, have moved to other positions on the X chromosome. Here, we summarize what is known about the regulation and function of Rhox cluster and Rhox-related genes during embryogenesis and gametogenesis. The founding member of the Rhox gene cluster--Rhox5 (previously known as Pem)--has been studied in the most depth and thus is the focus of this review. We also discuss the unusually rapid evolution of the Rhox gene cluster.
Topics: Animals; Embryonic Development; Female; Gametogenesis; Gene Expression Regulation; Genes, Homeobox; Mice; Multigene Family; Pregnancy; Transcription Factors
PubMed: 20430877
DOI: 10.1530/REP-10-0100 -
International Journal of Molecular... Jun 2021Mammals face environmental stressors throughout their lifespan, which may jeopardize cellular homeostasis. Hence, these organisms have acquired mechanisms to cope with... (Review)
Review
Mammals face environmental stressors throughout their lifespan, which may jeopardize cellular homeostasis. Hence, these organisms have acquired mechanisms to cope with stressors by sensing, repairing the damage, and reallocating resources to increase the odds of long-term survival. Autophagy is a pro-survival lysosome-mediated cytoplasm degradation pathway for organelle and macromolecule recycling. Furthermore, autophagy efflux increases, and this pathway becomes idiosyncratic depending upon developmental and environmental contexts. Mammalian germ cells and preimplantation embryos are attractive models for dissecting autophagy due to their metastable phenotypes during differentiation and exposure to varying environmental cues. The aim of this review is to explore autophagy during mammalian gametogenesis, fertilization and preimplantation embryonic development by contemplating its physiological role during development, under key stressors, and within the scope of assisted reproduction technologies.
Topics: Animals; Autophagy; Embryonic Development; Gametogenesis; Humans; Models, Biological; Oogenesis; Spermatogenesis
PubMed: 34204653
DOI: 10.3390/ijms22126313 -
Biology of Reproduction Sep 2021One of the most important developing cell types in any biological system is the gamete (sperm and egg). The transmission of phenotypes and optimally adapted physiology...
One of the most important developing cell types in any biological system is the gamete (sperm and egg). The transmission of phenotypes and optimally adapted physiology to subsequent generations is in large part controlled by gametogenesis. In contrast to genetics, the environment actively regulates epigenetics to impact the physiology and phenotype of cellular and biological systems. The integration of epigenetics and genetics is critical for all developmental biology systems at the cellular and organism level. The current review is focused on the role of epigenetics during gametogenesis for both the spermatogenesis system in the male and oogenesis system in the female. The developmental stages from the initial primordial germ cell through gametogenesis to the mature sperm and egg are presented. How environmental factors can influence the epigenetics of gametogenesis to impact the epigenetic transgenerational inheritance of phenotypic and physiological change in subsequent generations is reviewed.
Topics: Animals; Epigenesis, Genetic; Gametogenesis; Germ Cells; Inheritance Patterns; Male; Mice; Mice, Inbred C57BL
PubMed: 33929020
DOI: 10.1093/biolre/ioab085