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1.
Science ; 367(6479): 757-762, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-32054756

RESUMO

Clonal animals do not sequester a germ line during embryogenesis. Instead, they have adult stem cells that contribute to somatic tissues or gametes. How germ fate is induced in these animals, and whether this process is related to bilaterian embryonic germline induction, is unknown. We show that transcription factor AP2 (Tfap2), a regulator of mammalian germ lines, acts to commit adult stem cells, known as i-cells, to the germ cell fate in the clonal cnidarian Hydractinia symbiolongicarpus Tfap2 mutants lacked germ cells and gonads. Transplanted wild-type cells rescued gonad development but not germ cell induction in Tfap2 mutants. Forced expression of Tfap2 in i-cells converted them to germ cells. Therefore, Tfap2 is a regulator of germ cell commitment across germ line-sequestering and germ line-nonsequestering animals.


Assuntos
Células-Tronco Adultas/citologia , Gametogênese/fisiologia , Células Germinativas/citologia , Gônadas/embriologia , Hidrozoários/embriologia , Fator de Transcrição AP-2/fisiologia , Células-Tronco Adultas/metabolismo , Animais , Feminino , Gametogênese/genética , Regulação da Expressão Gênica no Desenvolvimento , Gônadas/citologia , Hidrozoários/citologia , Hidrozoários/genética , Masculino , Fator de Transcrição AP-2/genética
2.
Nat Commun ; 10(1): 4053, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492841

RESUMO

Whole genome sequencing (WGS) studies have estimated the human germline mutation rate per basepair per generation (~1.2 × 10-8) to be higher than in mice (3.5-5.4 × 10-9). In humans, most germline mutations are paternal in origin and numbers of mutations per offspring increase with paternal and maternal age. Here we estimate germline mutation rates and spectra in six multi-sibling mouse pedigrees and compare to three multi-sibling human pedigrees. In both species we observe a paternal mutation bias, a parental age effect, and a highly mutagenic first cell division contributing to the embryo. We also observe differences between species in mutation spectra, in mutation rates per cell division, and in the parental bias of mutations in early embryogenesis. These differences between species likely result from both species-specific differences in cellular genealogies of the germline, as well as biological differences within the same stage of embryogenesis or gametogenesis.


Assuntos
Células Germinativas/metabolismo , Mutação em Linhagem Germinativa , Taxa de Mutação , Sequenciamento Completo do Genoma/métodos , Animais , Divisão Celular/genética , Desenvolvimento Embrionário/genética , Feminino , Gametogênese/genética , Células Germinativas/citologia , Humanos , Masculino , Idade Materna , Camundongos , Idade Paterna , Linhagem , Especificidade da Espécie
3.
Plant Cell Physiol ; 60(11): 2436-2448, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31350548

RESUMO

Protoporphyrinogen IX oxidase1 (PPO1) catalyzes the oxidation of protoporphyrinogen IX to form protoporphyrin IX in the plastid tetrapyrrole biosynthesis pathway and is also essential for plastid RNA editing in Arabidopsis thaliana. The Arabidopsis ppo1-1 mutation was previously shown to be seedling lethal; however, in this study, we showed that the heterozygous ppo1-1/+ mutant exhibited reproductive growth defects characterized by reduced silique length and seed set, as well as aborted pollen development. In this mutant, the second mitotic division was blocked during male gametogenesis, whereas female gametogenesis was impaired at the one-nucleate stage. Before perishing at the seedling stage, the homozygous ppo1-1 mutant displayed reduced hypocotyl and root length, increased levels of reactive oxygen species accumulation and elevated cell death, especially under light conditions. Wild-type seedlings treated with acifluorfen, a PPO1 inhibitor, showed similar phenotypes to the ppo1-1 mutants, and both plants possessed a high proportion of 2C nuclei and a low proportion of 8C nuclei compared with the untreated wild type. Genome-wide RNA-seq analysis showed that a number of genes, including cell cycle-related genes, were differentially regulated by PPO1. Consistently, PPO1 was highly expressed in the pollen, anther, pistil and root apical meristem cells actively undergoing cell division. Our study reveals a role for PPO1 involved in the mitotic cell cycle during gametogenesis and seedling development.


Assuntos
Arabidopsis/metabolismo , Ciclo Celular/fisiologia , Cloroplastos/metabolismo , Arabidopsis/genética , Ciclo Celular/genética , Gametogênese/genética , Gametogênese/fisiologia , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Plastídeos/genética , Plastídeos/metabolismo
4.
Gen Comp Endocrinol ; 282: 113216, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31278920

RESUMO

The Atlantic Bluefin Tuna (ABFT, Thunnus thynnus) is one of the most intensely exploited fisheries resources in the world. In spite of the years of studies on ABFT, basic aspects of its reproductive biology remain uncertain. To gain insight regarding the seasonal changes of the reproductive characteristics of the eastern stock of ABFT, blood and tissue samples were collected from mature specimens caught in the Mediterranean basin during the reproductive (May-June) and non-reproductive season (Oct-Nov). Histological analysis of the gonads of May-June samples indicated that there were females which were actively spawning (contained post-ovulatory follicles) and females that were not actively spawning that had previtellogenic and fully vitellogenic oocytes. In males, testis were at early or late stage of spermatogenesis during the reproductive season. In Oct-Nov, ovaries contained mostly previtellogenic oocytes as well as ß and α atretic follicles while the testis predominantly contained spermatogonia and few cysts with spermatocytes and spermatozoa. Gonadosomatic index (GSI) in females was highest among the actively spawning individuals while in males GSI was higher in early and late spermatogenic individuals compared to those that were spent. Plasma sex steroids levels varied with the reproductive season. In females, estradiol (E2), was higher in May-June while testosterone (T) and progesterone (P) did not vary. In males, E2 and T were higher in May-June while P levels were similar at the two sampling points. Circulating follicle stimulating hormone (FSH) was higher in Oct-Nov than in May-June both in males and females. Vitellogenin (VTG) was detected in plasma from both males and females during the reproductive season with levels in females significantly higher than in males. VTG was undetected in Oct-Nov samples. Since choriogenesis is an important event during follicle growth, the expression of three genes involved in vitelline envelope formation and hardening was measured and results showed significantly higher levels in ovaries in fish caught in May-June with respect to those sampled in Oct-Nov. In addition, a set of genes encoding for ion channels that are responsible for oocyte hydration and buoyancy, as well as sperm viability, were characterized at the two time points, and these were found to be more highly expressed in females during the reproductive season. Finally, the expression level of three mRNAs encoding for different lipid-binding proteins was analyzed with significantly higher levels detected in males, suggesting sex-specific expression. Our findings provide additional information on the reproductive biology of ABFT, particularly on biomarkers for the assessment of the state of maturation of the gonad, highlighting gender-specific signals and seasonal differences.


Assuntos
Reprodução/fisiologia , Estações do Ano , Atum/fisiologia , Animais , Feminino , Hormônio Foliculoestimulante/sangue , Gametogênese/genética , Regulação da Expressão Gênica , Hormônios Esteroides Gonadais/metabolismo , Masculino , Folículo Ovariano/citologia , Ovário/citologia , Ovário/metabolismo , Testículo/citologia , Testículo/metabolismo , Atum/sangue , Atum/genética , Vitelogeninas/sangue
5.
Gene ; 698: 72-81, 2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-30825598

RESUMO

The edible sea urchin, Mesocentrotus nudus, is both an economically important mariculture species and an excellent model for studying reproductive development. The gonads are the only edible parts of sea urchins and increasing market demand for high-quality gonads has prompted increasing amounts of research into the molecular mechanisms of reproduction. Using a high-throughput sequencing technology, we performed transcriptome sequencing on the gonads of females and males, sampled before the spawning season, to identify genes involved in sex determination, sex differentiation and gametogenesis. Through a de novo transcriptome assembly approach, we obtained 104,039 unigenes, of which 40,471 (38.90%) showed homologies with known proteins in public databases. By comparing the expression levels of these unigenes in females and males, 15,368 differentially-expressed unigenes (DEGs) were identified. Compared with males, 9473 were up-regulated and 5895 were down-regulated in females. Multiple candidate genes were identified that may play important roles in spermatogenesis, oogenesis, and germ cell development. Furthermore, we identified and characterized several genes involved in sex determination and sex differentiation, such as dmrt1 and foxl2. The current study provides valuable molecular resources for studying the underlying mechanisms of reproduction in sea urchins.


Assuntos
Gametogênese/genética , Ouriços-do-Mar/genética , Diferenciação Sexual/genética , Animais , Desenvolvimento Embrionário/genética , Feminino , Proteína Forkhead Box L2/genética , Perfilação da Expressão Gênica/métodos , Gônadas , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , Oogênese/genética , Ovário , Análise para Determinação do Sexo/métodos , Processos de Determinação Sexual/genética , Fatores Sexuais , Espermatogênese/genética , Testículo , Fatores de Transcrição/genética , Transcriptoma
6.
Curr Top Dev Biol ; 132: 257-310, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30797511

RESUMO

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.


Assuntos
Células-Tronco Embrionárias/metabolismo , Fertilização/genética , Gametogênese/genética , Regulação da Expressão Gênica no Desenvolvimento , Células Germinativas/metabolismo , Animais , Diferenciação Celular/genética , Feminino , Humanos , Masculino
7.
Structure ; 27(4): 631-638.e8, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30773398

RESUMO

Histone methylation by histone methyltransferases (HMTases) has a key role in transcriptional regulation. Discrepancies between the known HMTases and the histone lysine methylome suggest that HMTases remain to be identified. Here we report the discovery, characterization, and crystal structure of Schizosaccharomyces pombe Set7, an HMTase methylating the uncharted histone H3 lysine 37 (H3K37) mark. Set7 forms a dimer with its substrate-binding site structurally specific to K37, not the neighboring well-studied K36 mark. We also discovered that H3K37 methylation levels dramatically increase during gametogenesis. Set7 deletion mutant cells show defects in gametogenesis and produce the abnormal number of spores with aberrant morphology. S. pombe gametogenesis shares similarities with mammalian spermatogenesis. These findings extend our understanding of epigenetic regulation during gametogenesis and support a link between Set7, the epigenetic H3K37 methyl mark, and proper gametogenesis.


Assuntos
Gametogênese/genética , Histona-Lisina N-Metiltransferase/genética , Histonas/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas de Schizosaccharomyces pombe/genética , Schizosaccharomyces/genética , Sequência de Aminoácidos , Epigênese Genética , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/genética , Metilação , Modelos Moleculares , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Schizosaccharomyces/crescimento & desenvolvimento , Schizosaccharomyces/metabolismo , Schizosaccharomyces/ultraestrutura , Proteínas de Schizosaccharomyces pombe/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Esporos Fúngicos/genética , Esporos Fúngicos/crescimento & desenvolvimento , Esporos Fúngicos/metabolismo , Esporos Fúngicos/ultraestrutura
8.
Tissue Cell ; 56: 7-13, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30736906

RESUMO

Successful gametogenesis in invertebrates is tightly associated with functioning of specific nutrient-storing cells. In oysters, cells of vesicular connective tissue (VCT-cells), also referred to as storage cells, which form a meshwork around gonadal acini, are the major population of cells that accumulate and provide nutrients for developing gametes. During the annual reproductive cycle, populations of developing germ cells and VCT-cells demonstrate the inversely proportional size dynamics: the larger the acini, the smaller the VCT-cells. In the present study, the morphology of VCT-cells in the Pacific oyster, Crassostrea gigas, at the active gametogenesis stage of reproductive cycle has been studied using light and transmission electron microscopy. At this stage, VCT-cells are big, irregularly shaped cells containing large nucleus with a single large nucleolus. The cytoplasm contains weakly developed endoplasmic reticulum, mitochondria in the perinuclear area and at periphery of the cell, numerous lipid droplets, and glycogen particles. Ultrastructure of VCT-cells is similar to the organization of brown adipocytes in mammals. The surface of cells has numerous cytoplasmic processes that are presumably associated with the transport function and provide close interaction with adjacent cells. The spatial relationship between VCT-cells and myoepithelial elements of the gonad area is demonstrated and discussed.


Assuntos
Células Germinativas/metabolismo , Gônadas/metabolismo , Nutrientes/metabolismo , Ostreidae/metabolismo , Animais , Gametogênese/genética , Células Germinativas/crescimento & desenvolvimento , Gônadas/anatomia & histologia , Ostreidae/anatomia & histologia , Reprodução/genética
9.
Mar Biotechnol (NY) ; 21(2): 196-205, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30680591

RESUMO

DNA methylation reprograms during gametogenesis and embryo development, which is essential for germ cell specification and genomic imprinting in mammals. Corresponding process remains poorly investigated in molluscs. Here, we examined global DNA methylation level in the gonads of scallop Patinopecten yessoensis during gametogenesis and in embryos/larvae at different stages. DNA methylation level fluctuates during gametogenesis and early development, peaking at proliferative stage of ovary, growing stage of testis, and in blastulae. To understand the mechanisms underlying these changes, we conducted genome-wide characterization of DNMT family and investigated their expression profiles based on transcriptomes and in situ hybridization. Three genes were identified, namely PyDNMT1, PyDNMT2, and PyDNMT3. Expression of PyDnmt3 agrees with DNA methylation level during oogenesis and early development, suggesting PyDNMT3 may participate in de novo DNA methylation that occurs mainly at proliferative stage of ovary and testis, and in blastulae and gastrulae. PyDnmt1 expression is positively correlated with DNA methylation level during spermatogenesis, and is higher at maturation stage of ovary and in 2-8 cell embryos than other stages, implying possible involvement of PyDNMT1 in DNA methylation maintenance during meiosis and embryonic development. This study will facilitate better understanding of the developmental epigenetic reprogramming in bivalve molluscs.


Assuntos
Metilação de DNA/genética , Gametogênese/genética , Pectinidae/embriologia , Pectinidae/crescimento & desenvolvimento , Animais , Embrião não Mamífero , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Metiltransferases , Ovário/crescimento & desenvolvimento , Pectinidae/genética , Testículo/crescimento & desenvolvimento
10.
Genome Biol Evol ; 11(1): 295-318, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30535381

RESUMO

Stolonization in syllid annelids is a unique mode of reproduction among animals. During the breeding season, a structure resembling the adult but containing only gametes, called stolon, is formed generally at the posterior end of the animal. When stolons mature, they detach from the adult and gametes are released into the water column. The process is synchronized within each species, and it has been reported to be under environmental and endogenous control, probably via endocrine regulation. To further understand reproduction in syllids and to elucidate the molecular toolkit underlying stolonization, we generated Illumina RNA-seq data from different tissues of reproductive and nonreproductive individuals of Syllis magdalena and characterized gene expression during the stolonization process. Several genes involved in gametogenesis (ovochymase, vitellogenin, testis-specific serine/threonine-kinase), immune response (complement receptor 2), neuronal development (tyrosine-protein kinase Src42A), cell proliferation (alpha-1D adrenergic receptor), and steroid metabolism (hydroxysteroid dehydrogenase 2) were found differentially expressed in the different tissues and conditions analyzed. In addition, our findings suggest that several neurohormones, such as methyl farnesoate, dopamine, and serotonin, might trigger stolon formation, the correct maturation of gametes and the detachment of stolons when gametogenesis ends. The process seems to be under circadian control, as indicated by the expression patterns of r-opsins. Overall, our results shed light into the genes that orchestrate the onset of gamete formation and improve our understanding of how some hormones, previously reported to be involved in reproduction and metamorphosis processes in other invertebrates, seem to also regulate reproduction via stolonization.


Assuntos
Gametogênese/genética , Poliquetos/fisiologia , Animais , Feminino , Expressão Gênica , Hormônios/fisiologia , Masculino , Poliquetos/ultraestrutura , Transcriptoma
11.
Plant Cell Rep ; 38(1): 59-74, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30341574

RESUMO

KEY MESSAGE: Loss-of-function of nucleoporin NUP1 in Arabidopsis causes defect in both male and female gametogenesis. Its ovules are arrested during meiosis, and its pollen grains are aborted at mitosis I. Nuclear pore complex (NPC) plays crucial roles in nucleocytoplasmic trafficking of proteins and RNAs. The NPC contains approximately 30 different proteins termed nucleoporins (NUPs). So far, only a few of plant NUPs have been characterized. The Arabidopsis NUP1 was identified as an ortholog of the yeast NUP1 and animal NUP153. Loss-of-function of NUP1 in Arabidopsis caused fertility defect; however, the molecular mechanism of this defect remains unknown. Here, we found that both male and female gametogenesis of the nup1 mutants were defective. nup1 ovules were arrested from the meiosis stage onward; only approximately 6.7% and 3% ovules of the nup1-1 and nup1-4 mutants developed up to the FG7 stage, respectively. Pollen development of the nup1 mutants was arrested during the first mitotic division. In addition, enlarged pollen grains with increased DNA content were observed in the nup1 mutant. RNA-sequencing showed that expression levels of genes involved in pollen development or regulation of cell size were reduced dramatically in nup1 compared with wild type. These results suggest that NUP1 plays an important role in gametogenesis.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Arabidopsis/fisiologia , Pólen/metabolismo , Pólen/fisiologia , Proteínas de Arabidopsis/genética , Gametogênese/genética , Gametogênese/fisiologia , Poro Nuclear/genética , Poro Nuclear/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo
12.
PLoS Genet ; 14(11): e1007836, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30475921

RESUMO

Meiotic drivers are selfish alleles that subvert gametogenesis to increase their transmission into progeny. Drivers impose a fitness cost, putting pressure on the genome to evolve suppressors. Here we investigate the wtf gene family from Schizosaccharomyces pombe, previously shown to contain meiotic drivers in wild isolates. We discovered that wtf13 found in lab stocks is a meiotic driver. wtf13 kills spores that do not inherit it by generating both a diffusible poison and a spore-specific antidote. Additionally, we demonstrate that wtf13 is suppressed by another wtf gene, wtf18-2, that arose spontaneously in the lab and makes only an antidote. Wtf18-2 does not act indiscriminately to prevent spore destruction. Instead, it rescues only the spores that inherit wtf18-2. In this way, wtf18-2 selfishly gains a transmission advantage of its own while dampening the drive of wtf13. This establishes a novel paradigm for meiotic drive suppressors and provides insight into the mechanisms and evolution of drive systems.


Assuntos
Genes Fúngicos , Meiose/genética , Schizosaccharomyces/genética , Alelos , Sequência de Aminoácidos , Antídotos , Gametogênese/genética , Modelos Genéticos , Mimetismo Molecular/genética , Família Multigênica , Venenos , Sequências Repetitivas de Ácido Nucleico , Schizosaccharomyces/citologia , Proteínas de Schizosaccharomyces pombe/genética , Homologia de Sequência de Aminoácidos , Esporos Fúngicos/genética , Supressão Genética
13.
Nat Commun ; 9(1): 4155, 2018 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-30297796

RESUMO

The preservation of germ cell sexual identity is essential for gametogenesis. Here we show that H3K9me3-mediated gene silencing is integral to female fate maintenance in Drosophila germ cells. Germ cell specific loss of the H3K9me3 pathway members, the H3K9 methyltransferase SETDB1, WDE, and HP1a, leads to ectopic expression of genes, many of which are normally expressed in testis. SETDB1 controls the accumulation of H3K9me3 over a subset of these genes without spreading into neighboring loci. At phf7, a regulator of male germ cell sexual fate, the H3K9me3 peak falls over the silenced testis-specific transcription start site. Furthermore, H3K9me3 recruitment to phf7 and repression of testis-specific transcription is dependent on the female sex determination gene Sxl. Thus, female identity is secured by an H3K9me3 epigenetic pathway in which Sxl is the upstream female-specific regulator, SETDB1 is the required chromatin writer, and phf7 is one of the critical SETDB1 target genes.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Células Germinativas/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Animais , Animais Geneticamente Modificados , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Feminino , Gametogênese/genética , Regulação da Expressão Gênica no Desenvolvimento , Inativação Gênica , Histona-Lisina N-Metiltransferase/genética , Histonas/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Lisina/metabolismo , Masculino , Metilação , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
14.
Nat Microbiol ; 3(11): 1206-1213, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30177743

RESUMO

During malaria infection, Plasmodium spp. parasites cyclically invade red blood cells and can follow two different developmental pathways. They can either replicate asexually to sustain the infection, or differentiate into gametocytes, the sexual stage that can be taken up by mosquitoes, ultimately leading to disease transmission. Despite its importance for malaria control, the process of gametocytogenesis remains poorly understood, partially due to the difficulty of generating high numbers of sexually committed parasites in laboratory conditions1. Recently, an apicomplexa-specific transcription factor (AP2-G) was identified as necessary for gametocyte production in multiple Plasmodium species2,3, and suggested to be an epigenetically regulated master switch that initiates gametocytogenesis4,5. Here we show that in a rodent malaria parasite, Plasmodium berghei, conditional overexpression of AP2-G can be used to synchronously convert the great majority of the population into fertile gametocytes. This discovery allowed us to redefine the time frame of sexual commitment, identify a number of putative AP2-G targets and chart the sequence of transcriptional changes through gametocyte development, including the observation that gender-specific transcription occurred within 6 h of induction. These data provide entry points for further detailed characterization of the key process required for malaria transmission.


Assuntos
Gametogênese/genética , Regulação da Expressão Gênica no Desenvolvimento , Malária/parasitologia , Plasmodium berghei/genética , Animais , Eritrócitos/parasitologia , Feminino , Perfilação da Expressão Gênica , Camundongos , Plasmodium berghei/fisiologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
15.
Hum Reprod Update ; 24(5): 556-576, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29992283

RESUMO

BACKGROUND: Over the past few years, advances in molecular technologies have allowed unprecedented mapping of epigenetic modifications in gametes and during early embryonic development. This work is allowing a detailed genomic analysis, which for the first time can answer long-standing questions about epigenetic regulation and reprogramming, and highlights differences between mouse and human, the implications of which are only beginning to be explored. OBJECTIVE AND RATIONALE: In this review, we summarise new low-cell molecular methods enabling the interrogation of epigenetic information in gametes and early embryos, the mechanistic insights these have provided, and contrast the findings in mouse and human. SEARCH METHODS: Relevant studies were identified by PubMed search. OUTCOMES: We discuss the levels of epigenetic regulation, from DNA modifications to chromatin organisation, during mouse gametogenesis, fertilisation and pre- and post-implantation development. The recently characterised features of the oocyte epigenome highlight its exceptionally unique regulatory landscape. The chromatin organisation and epigenetic landscape of both gametic genomes are rapidly reprogrammed after fertilisation. This extensive epigenetic remodelling is necessary for zygotic genome activation, but the mechanistic link remains unclear. While the vast majority of epigenetic information from the gametes is erased in pre-implantation development, new insights suggest that repressive histone modifications from the oocyte may mediate a novel mechanism of imprinting. To date, the characterisation of epigenetics in human development has been almost exclusively limited to DNA methylation profiling; these data reinforce that the global dynamics are conserved between mouse and human. However, as we look closer, it is becoming apparent that the mechanisms regulating these dynamics are distinct. These early findings emphasise the importance of investigations of fundamental epigenetic mechanisms in both mouse and humans. WIDER IMPLICATIONS: Failures in epigenetic regulation have been implicated in human disease and infertility. With increasing maternal age and use of reproductive technologies in countries all over the world, it is becoming ever more important to understand the necessary processes required to establish a developmentally competent embryo. Furthermore, it is essential to evaluate the extent to which these epigenetic patterns are sensitive to such technologies and other adverse environmental exposures.


Assuntos
Desenvolvimento Embrionário/genética , Epigênese Genética , Camundongos , Animais , Metilação de DNA , Feminino , Gametogênese/genética , Impressão Genômica , Genômica , Células Germinativas , Humanos , Infertilidade/genética , Modelos Animais , Gravidez , Complicações na Gravidez/genética , Processamento de Proteína Pós-Traducional
16.
Biol Reprod ; 99(6): 1119-1128, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29878059

RESUMO

Gene mutations, including different alleles of the same gene, are tremendously useful in deconstructing complex developmental systems, such as reproduction, into component molecular pathways. For this reason, great effort has been devoted in the past three decades to biased (reverse genetic) and unbiased (forward genetic) searches for new genes that impact mammalian reproduction and fertility. These efforts have more recently been complemented with international efforts to systematically mutate all mouse genes and to determine their phenotypes (essentially a hybrid of forward and reverse genetics). Here, we survey the available data on the relative productivity of these approaches in identifying fertility genes, estimate the number of protein-coding genes essential for fertility of males and females, and predict the next major directions in the genetics of reproduction and fertility.


Assuntos
Fertilidade/genética , Regulação da Expressão Gênica/fisiologia , Infertilidade/genética , Animais , Gametogênese/genética , Gametogênese/fisiologia , Humanos , Mutação
17.
Genome Biol Evol ; 10(6): 1430-1444, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29850809

RESUMO

Gonadal sex differentiation and reproduction are the keys to the perpetuation of favorable gene combinations and positively selected traits. In vertebrates, several gonad development features that differentiate tetrapods and fishes are likely to be, at least in part, related to the water-to-land transition. The collection of information from basal sarcopterygians, coelacanths, and lungfishes, is crucial to improve our understanding of the molecular evolution of pathways involved in reproductive functions, since these organisms are generally regarded as "living fossils" and as the direct ancestors of tetrapods. Here, we report for the first time the characterization of >50 genes related to sex differentiation and gametogenesis in Latimeria menadoensis and Protopterus annectens. Although the expression profiles of most genes is consistent with the intermediate position of basal sarcopterygians between actinopterygian fish and tetrapods, their phylogenetic placement and presence/absence patterns often reveal a closer affinity to the tetrapod orthologs. On the other hand, particular genes, for example, the male gonad factor gsdf (Gonadal Soma-Derived Factor), provide examples of ancestral traits shared with actinopterygians, which disappeared in the tetrapod lineage.


Assuntos
Cordados/genética , Peixes/genética , Gametogênese/genética , Diferenciação Sexual/genética , Animais , Evolução Molecular , Masculino , Filogenia , Reprodução/genética
18.
Gene ; 668: 33-47, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-29758296

RESUMO

The Pacific white shrimp Penaeus vannamei is the most cultured shrimp species around the world. Because females grow larger than males, the culture of 'only females' is of great interest, but knowledge on sex determination and differentiation is required for producing only females. In an effort to obtain information associated with reproduction in P. vannamei, transcriptomic data from female gonads was generated, and partial sequences of a transcript were identified as Sex-lethal (Sxl). Its characterization indicated that, differently from other penaeids in which this gene has been isolated, there are six isoforms of the Sxl transcript in P. vannamei (PvanSxl 1-6). These isoforms result from alternative splicing at three splice sites (SS1, SS2, SS3). The first splice-site is unique to P. vannamei, as it has not been reported for other Arthropod species; the second splice-site (SS2) is common among crustaceans, and the third splice-site (SS3) is also unique to P. vannamei and when spliced-out, it is always together with SS2. All isoforms are expressed during embryogenesis as well as gametogenesis of both genders. The two shorter isoforms, PvanSxl-5 and PvanSxl-6, which result from the splicing of SS2 and SS3, were found mostly expressed in adult testis, but PvanSxl-6 was also expressed in oocytes during gametogenesis. During oogenesis, the second largest isoform, PvanSxl-2, which splices-out only SS1, and PvanSxl-4 that splices-out SS1 and SS2 were highly expressed. These two isoforms were also highly expressed during embryonic development. In situ hybridization allowed pinpointing more specifically the cells where the PvanSxl transcripts were expressed. During embryogenesis, hybridization was observed from the one-cell stage embryo to late gastrula. In the female gonad in previtellogenesis, hybridization occurred in the nucleus of oocytes, whereas in secondary vitellogenesis the transcript also hybridized cytoplasmic granules and cortical crypts. Finally, in situ hybridization corroborated the expression of PvanSxl also in the male gonad during spermatogenesis, mostly occurring in the cytoplasm from spermatogonia and spermatocytes.


Assuntos
Proteínas de Artrópodes/genética , Penaeidae/fisiologia , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/química , Proteínas de Artrópodes/classificação , Proteínas de Artrópodes/metabolismo , Desenvolvimento Embrionário/genética , Feminino , Gametogênese/genética , Gônadas/metabolismo , Masculino , Especificidade de Órgãos , Penaeidae/embriologia , Penaeidae/genética , Penaeidae/crescimento & desenvolvimento , Filogenia , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Alinhamento de Sequência
19.
Nature ; 555(7696): 392-396, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29513657

RESUMO

Gametes are highly specialized cells that can give rise to the next generation through their ability to generate a totipotent zygote. In mice, germ cells are first specified in the developing embryo around embryonic day (E) 6.25 as primordial germ cells (PGCs). Following subsequent migration into the developing gonad, PGCs undergo a wave of extensive epigenetic reprogramming around E10.5-E11.5, including genome-wide loss of 5-methylcytosine. The underlying molecular mechanisms of this process have remained unclear, leading to our inability to recapitulate this step of germline development in vitro. Here we show, using an integrative approach, that this complex reprogramming process involves coordinated interplay among promoter sequence characteristics, DNA (de)methylation, the polycomb (PRC1) complex and both DNA demethylation-dependent and -independent functions of TET1 to enable the activation of a critical set of germline reprogramming-responsive genes involved in gamete generation and meiosis. Our results also reveal an unexpected role for TET1 in maintaining but not driving DNA demethylation in gonadal PGCs. Collectively, our work uncovers a fundamental biological role for gonadal germline reprogramming and identifies the epigenetic principles of the PGC-to-gonocyte transition that will help to guide attempts to recapitulate complete gametogenesis in vitro.


Assuntos
Reprogramação Celular/genética , Epigênese Genética , Gametogênese/genética , Células Germinativas/citologia , Células Germinativas/metabolismo , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Animais , Metilação de DNA , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Masculino , Meiose , Camundongos , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo
20.
Science ; 359(6381): 1259-1263, 2018 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-29590075

RESUMO

Malaria is caused by Plasmodium parasites that proliferate in the bloodstream. During each replication cycle, some parasites differentiate into gametocytes, the only forms able to infect the mosquito vector and transmit malaria. Sexual commitment is triggered by activation of AP2-G, the master transcriptional regulator of gametocytogenesis. Heterochromatin protein 1 (HP1)-dependent silencing of ap2-g prevents sexual conversion in proliferating parasites. In this study, we identified Plasmodium falciparum gametocyte development 1 (GDV1) as an upstream activator of sexual commitment. We found that GDV1 targeted heterochromatin and triggered HP1 eviction, thus derepressing ap2-g Expression of GDV1 was responsive to environmental triggers of sexual conversion and controlled via a gdv1 antisense RNA. Hence, GDV1 appears to act as an effector protein that induces sexual differentiation by antagonizing HP1-dependent gene silencing.


Assuntos
Proteínas Cromossômicas não Histona/metabolismo , Gametogênese/genética , Inativação Gênica , Malária Falciparum/parasitologia , Plasmodium falciparum/crescimento & desenvolvimento , Diferenciação Sexual/genética , Animais , Plasmodium falciparum/genética
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