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Comptes Rendus Biologies Jun 2024Fertility is declining worldwide and many couples are turning towards assisted reproductive technologies (ART) to conceive babies. Organisms that propagate via sexual... (Review)
Review
Fertility is declining worldwide and many couples are turning towards assisted reproductive technologies (ART) to conceive babies. Organisms that propagate via sexual reproduction often come from the fusion between two gametes, an oocyte and a sperm, whose qualities seem to be decreasing in the human species. Interestingly, while the sperm mostly transmits its haploid genome, the oocyte transmits not only its haploid set of chromosomes but also its huge cytoplasm to its progeny. This is what can be defined as the maternal inheritance composed of chromosomes, organelles, lipids, metabolites, proteins and RNAs. To decipher the decline in oocyte quality, it is essential to explore the nature of the maternal inheritance, and therefore study the last stages of murine oogenesis, namely the end of oocyte growth followed by the two meiotic divisions. These divisions are extremely asymmetric in terms of the size of the daughter cells, allowing to preserve the maternal inheritance accumulated during oocyte growth within these huge cells to support early embryo development. Studies performed in Marie-Hélène Verlhac's lab have allowed to discover the unprecedented impact of original acto-myosin based mechanisms in the constitution as well as the preservation of this maternal inheritance and the consequences when these processes go awry.
Topics: Animals; Female; Humans; Mice; Maternal Inheritance; Meiosis; Oocytes; Oogenesis
PubMed: 38888193
DOI: 10.5802/crbiol.155 -
Frontiers in Endocrinology 2024Anti-Müllerian hormone (AMH) is a key paracrine/autocrine factor regulating folliculogenesis in the postnatal ovary. As antral follicles mature to the preovulatory...
Anti-Müllerian hormone (AMH) is a key paracrine/autocrine factor regulating folliculogenesis in the postnatal ovary. As antral follicles mature to the preovulatory stage, AMH production tends to be limited to cumulus cells. Therefore, the present study investigated the role of cumulus cell-derived AMH in supporting maturation and competence of the enclosed oocyte. Cumulus-oocyte complexes (COCs) were isolated from antral follicles of rhesus macaque ovaries for maturation with or without AMH depletion. Oocyte meiotic status and embryo cleavage after fertilization were assessed. maturation with AMH depletion was also performed using COCs from antral follicles of human ovarian tissue. Oocyte maturation and morphology were evaluated. The direct AMH action on mural granulosa cells of the preovulatory follicle was further assessed using human granulosa cells cultured with or without AMH supplementation. More macaque COCs produced metaphase II oocytes with AMH depletion than those of the control culture. However, preimplantation embryonic development after fertilization was comparable between oocytes derived from COCs cultured with AMH depletion and controls. Oocytes resumed meiosis in human COCs cultured with AMH depletion and exhibited a typical spindle structure. The confluency and cell number decreased in granulosa cells cultured with AMH supplementation relative to the control culture. AMH treatment did not induce cell death in cultured human granulosa cells. Data suggest that reduced AMH action in COCs could be beneficial for oocyte maturation. Cumulus cell-derived AMH is not essential for supporting oocyte competence or mural granulosa cell viability.
Topics: Anti-Mullerian Hormone; Oocytes; Female; Cumulus Cells; Animals; Humans; In Vitro Oocyte Maturation Techniques; Macaca mulatta; Oogenesis; Cells, Cultured; Fertilization in Vitro; Meiosis; Granulosa Cells; Ovarian Follicle; Embryonic Development
PubMed: 38887270
DOI: 10.3389/fendo.2024.1365260 -
Molecular Biology and Evolution Jun 2024Although evolution is driven by changes in how regulatory pathways control development, we know little about the molecular details underlying these transitions. The...
Although evolution is driven by changes in how regulatory pathways control development, we know little about the molecular details underlying these transitions. The TRA-2 domain that mediates contact with TRA-1 is conserved in Caenorhabditis. By comparing the interaction of these proteins in two species, we identified a striking change in how sexual development is controlled. Identical mutations in this domain promote oogenesis in Caenorhabditis elegans but promote spermatogenesis in Caenorhabditis briggsae. Furthermore, the effects of these mutations involve the male-promoting gene fem-3 in C. elegans but are independent of fem-3 in C. briggsae. Finally, reciprocal mutations in these genes show that C. briggsae TRA-2 binds TRA-1 to prevent expression of spermatogenesis regulators. By contrast, in C. elegans TRA-1 sequesters TRA-2 in the germ line, allowing FEM-3 to initiate spermatogenesis. Thus, we propose that the flow of information within the sex determination pathway has switched directions during evolution. This result has important implications for how evolutionary change can occur.
Topics: Animals; Caenorhabditis elegans Proteins; Sex Determination Processes; Caenorhabditis elegans; Male; Spermatogenesis; Female; Caenorhabditis; Biological Evolution; RNA-Binding Proteins; Mutation; Oogenesis; Evolution, Molecular; Self-Fertilization; DNA-Binding Proteins; Transcription Factors
PubMed: 38880992
DOI: 10.1093/molbev/msae101 -
Animal Cells and Systems 2024The system forming ovarian follicles is developed to investigate folliculogenesis in a confined environment to obtain functional oocytes. Several studies have reported...
The system forming ovarian follicles is developed to investigate folliculogenesis in a confined environment to obtain functional oocytes. Several studies have reported the successful generation of fully functional oocytes using mouse-induced pluripotent stem cells (iPSCs) and mouse female germline stem cells (fGSCs) as sources of stem cells for gametogenesis models. In addition, human oogonia have been generated through heterologous co-culture of differentiated human primordial germ cell-like cells (hPGCLCs) with mouse germline somatic cells, although oocyte formation remains challenging. Thus, studies on ovarian formation in other species are utilized as an introductory approach for mammalian gametogenesis by understanding the differences in culture systems between species and underlying mechanisms. In this study, we optimized the method of the entire oogenesis process from rat embryonic gonads. We identified well-maturated MII oocytes from rat gonads using our constructed method. Moreover, we generated the first successful reconstitution of xenogeneic follicles from mouse primordial germ cells (PGCs) and rat somatic cells. We also established an appropriate culture medium and incubation period for xenogeneic follicles. This method will be helpful in studies of xenogeneic follicular development and oocyte generation.
PubMed: 38868077
DOI: 10.1080/19768354.2024.2363601 -
Genes & Development Jun 2024Genome organization can regulate gene expression and promote cell fate transitions. The differentiation of germline stem cells (GSCs) to oocytes in involves changes in...
Genome organization can regulate gene expression and promote cell fate transitions. The differentiation of germline stem cells (GSCs) to oocytes in involves changes in genome organization mediated by heterochromatin and the nuclear pore complex (NPC). Heterochromatin represses germ cell genes during differentiation, and NPCs anchor these silenced genes to the nuclear periphery, maintaining silencing to allow for oocyte development. Surprisingly, we found that genome organization also contributes to NPC formation, mediated by the transcription factor Stonewall (Stwl). As GSCs differentiate, Stwl accumulates at boundaries between silenced and active gene compartments. Stwl at these boundaries plays a pivotal role in transitioning germ cell genes into a silenced state and activating a group of oocyte genes and nucleoporins (Nups). The upregulation of these Nups during differentiation is crucial for NPC formation and further genome organization. Thus, cross-talk between genome architecture and NPCs is essential for successful cell fate transitions.
Topics: Animals; Oogenesis; Drosophila Proteins; Cell Differentiation; Nuclear Pore; Genome, Insect; Gene Expression Regulation, Developmental; Female; Drosophila melanogaster; Oocytes; Transcription Factors; Drosophila; Nuclear Pore Complex Proteins
PubMed: 38866556
DOI: 10.1101/gad.351402.123 -
BMC Genomics Jun 2024Gibel carp (Carassius gibelio) is a cyprinid fish that originated in eastern Eurasia and is considered as invasive in European freshwater ecosystems. The populations of...
Reproduction-associated pathways in females of gibel carp (Carassius gibelio) shed light on the molecular mechanisms of the coexistence of asexual and sexual reproduction.
Gibel carp (Carassius gibelio) is a cyprinid fish that originated in eastern Eurasia and is considered as invasive in European freshwater ecosystems. The populations of gibel carp in Europe are mostly composed of asexually reproducing triploid females (i.e., reproducing by gynogenesis) and sexually reproducing diploid females and males. Although some cases of coexisting sexual and asexual reproductive forms are known in vertebrates, the molecular mechanisms maintaining such coexistence are still in question. Both reproduction modes are supposed to exhibit evolutionary and ecological advantages and disadvantages. To better understand the coexistence of these two reproduction strategies, we performed transcriptome profile analysis of gonad tissues (ovaries) and studied the differentially expressed reproduction-associated genes in sexual and asexual females. We used high-throughput RNA sequencing to generate transcriptomic profiles of gonadal tissues of triploid asexual females and males, diploid sexual males and females of gibel carp, as well as diploid individuals from two closely-related species, C. auratus and Cyprinus carpio. Using SNP clustering, we showed the close similarity of C. gibelio and C. auratus with a basal position of C. carpio to both Carassius species. Using transcriptome profile analyses, we showed that many genes and pathways are involved in both gynogenetic and sexual reproduction in C. gibelio; however, we also found that 1500 genes, including 100 genes involved in cell cycle control, meiosis, oogenesis, embryogenesis, fertilization, steroid hormone signaling, and biosynthesis were differently expressed in the ovaries of asexual and sexual females. We suggest that the overall downregulation of reproduction-associated pathways in asexual females, and their maintenance in sexual ones, allows the populations of C. gibelio to combine the evolutionary and ecological advantages of the two reproductive strategies. However, we showed that many sexual-reproduction-related genes are maintained and expressed in asexual females, suggesting that gynogenetic gibel carp retains the genetic toolkits for meiosis and sexual reproduction. These findings shed new light on the evolution of this asexual and sexual complex.
Topics: Animals; Female; Reproduction, Asexual; Reproduction; Carps; Male; Transcriptome; Gene Expression Profiling; Ovary; Polymorphism, Single Nucleotide
PubMed: 38824502
DOI: 10.1186/s12864-024-10462-4 -
Molecular Aspects of Medicine Jun 2024Meiosis is a critical step for spermatogenesis and oogenesis. Meiosis commences with pre-meiotic S phase that is subsequently followed by meiotic prophase. The meiotic... (Review)
Review
Meiosis is a critical step for spermatogenesis and oogenesis. Meiosis commences with pre-meiotic S phase that is subsequently followed by meiotic prophase. The meiotic prophase is characterized by the meiosis-specific chromosomal events such as chromosome recombination and homolog synapsis. Meiosis initiator (MEIOSIN) and stimulated by retinoic acid gene 8 (STRA8) initiate meiosis by activating the meiotic genes by installing the meiotic prophase program at pre-meiotic S phase. This review highlights the mechanisms of meiotic initiation and meiotic prophase progression from the point of the gene expression program and its relevance to infertility. Furthermore, upstream pathways that regulate meiotic initiation will be discussed in the context of spermatogenic development, indicating the sexual differences in the mode of meiotic entry.
Topics: Spermatogenesis; Humans; Meiosis; Animals; Male; Meiotic Prophase I; Prophase
PubMed: 38797021
DOI: 10.1016/j.mam.2024.101282 -
Biomolecules Apr 2024Suppressor of deltex () is a member of the NEDD4 family of the HECT domain E3 ubiquitin ligases. acts as a regulator of Notch endocytic trafficking, promoting Notch...
Suppressor of deltex () is a member of the NEDD4 family of the HECT domain E3 ubiquitin ligases. acts as a regulator of Notch endocytic trafficking, promoting Notch lysosomal degradation and the down-regulation of both ligand-dependent and ligand-independent signalling, the latter involving trafficking through the endocytic pathway and activation of the endo/lysosomal membrane. Mutations of result in developmental phenotypes in the wing that reflect increased Notch signalling, leading to gaps in the specification of the wing veins, and functions to provide the developmental robustness of Notch activity to environmental temperature shifts. The full developmental functions of are unclear; however, this is due to a lack of a clearly defined null allele. Here we report the first defined null mutation of , generated by P-element excision, which removes the complete open reading frame. We show that the mutation is recessive-viable, with the Notch gain of function phenotypes affecting wing vein and leg development. We further uncover new roles for in oogenesis, where it regulates interfollicular stalk formation, egg chamber separation and germline cyst enwrapment by the follicle stem cells. Interestingly, while the null allele exhibited a gain in Notch activity during oogenesis, the previously described allele, which carries a seven amino acid in-frame deletion, displayed a Notch loss of function phenotypes and an increase in follicle stem cell turnover. This is despite both alleles displaying similar Notch gain of function in wing development. We attribute this unexpected context-dependent outcome of being due to the partial retention of function by the intact C2 and WW domain regions of the protein. Our results extend our understanding of the developmental role of in the tissue renewal and homeostasis of the ovary and illustrate the importance of examining an allelic series of mutations to fully understand developmental functions.
Topics: Animals; Oogenesis; Drosophila melanogaster; Drosophila Proteins; Receptors, Notch; Alleles; Female; Wings, Animal; Mutation; Signal Transduction; Phenotype; Membrane Proteins
PubMed: 38785929
DOI: 10.3390/biom14050522 -
Journal of Pregnancy 2024The cannabinoid receptor (CBR) plays a significant role in oogenesis, pregnancy, and childbirth. It might also play a significant role in preterm birth (PTB). The aim... (Observational Study)
Observational Study
The cannabinoid receptor (CBR) plays a significant role in oogenesis, pregnancy, and childbirth. It might also play a significant role in preterm birth (PTB). The aim of the study was to investigate the association between the expression of the CBR in the placenta and the incidence of PTB. This prospective, observational, multicentre preliminary study was conducted on placental samples obtained from 109 women. The study included 95 patients hospitalized due to the high risk of PTB. They were divided into two groups: Group 1, where the expression of the CBR1 and CBR1a was analyzed, and Group 2, in which we examined CBR2 expression. The control group, that is, Group 3, consisted of 14 women who delivered at term, and their placentas were tested for the presence of all three receptor types (CBR1, CBR1a, and CBR2). The study used reverse transcription and real-time PCR methods to assess the expression of CBRs in the placental tissues. The expression of the CBR2, CBR1, and CBR1a receptors was significantly lower in the placentas of women after PTB compared to those after term births, = 0.038, 0.033, and 0.034, respectively. The presence of CBR mRNA in the human placental tissue was confirmed. The decreased expression of CBRs could serve as an indicator in predicting PTB.
Topics: Humans; Female; Pregnancy; Placenta; Premature Birth; Prospective Studies; Adult; Receptor, Cannabinoid, CB2; Receptor, Cannabinoid, CB1; Case-Control Studies; RNA, Messenger; Receptors, Cannabinoid
PubMed: 38745869
DOI: 10.1155/2024/6620156 -
PLoS Biology May 2024Animals are influenced by the season, yet we know little about the changes that occur in most species throughout the year. This is particularly true in tropical marine...
Animals are influenced by the season, yet we know little about the changes that occur in most species throughout the year. This is particularly true in tropical marine animals that experience relatively small annual temperature and daylight changes. Like many coral reef inhabitants, the crown-of-thorns starfish (COTS), well known as a notorious consumer of corals and destroyer of coral reefs, reproduces exclusively in the summer. By comparing gene expression in 7 somatic tissues procured from wild COTS sampled on the Great Barrier Reef, we identified more than 2,000 protein-coding genes that change significantly between summer and winter. COTS genes that appear to mediate conspecific communication, including both signalling factors released into the surrounding sea water and cell surface receptors, are up-regulated in external secretory and sensory tissues in the summer, often in a sex-specific manner. Sexually dimorphic gene expression appears to be underpinned by sex- and season-specific transcription factors (TFs) and gene regulatory programs. There are over 100 TFs that are seasonally expressed, 87% of which are significantly up-regulated in the summer. Six nuclear receptors are up-regulated in all tissues in the summer, suggesting that systemic seasonal changes are hormonally controlled, as in vertebrates. Unexpectedly, there is a suite of stress-related chaperone proteins and TFs, including HIFa, ATF3, C/EBP, CREB, and NF-κB, that are uniquely and widely co-expressed in gravid females. The up-regulation of these stress proteins in the summer suggests the demands of oogenesis in this highly fecund starfish affects protein stability and turnover in somatic cells. Together, these circannual changes in gene expression provide novel insights into seasonal changes in this coral reef pest and have the potential to identify vulnerabilities for targeted biocontrol.
Topics: Animals; Seasons; Starfish; Reproduction; Female; Male; Stress, Physiological; Gene Expression Regulation; Transcription Factors; Organ Specificity; Coral Reefs
PubMed: 38743647
DOI: 10.1371/journal.pbio.3002620