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Life (Basel, Switzerland) Jun 2024The phosphoinositide 3-kinase (PI3K)/Akt pathway is a key signaling cascade responsible for the regulation of cell survival, proliferation, and metabolism in the ovarian... (Review)
Review
The phosphoinositide 3-kinase (PI3K)/Akt pathway is a key signaling cascade responsible for the regulation of cell survival, proliferation, and metabolism in the ovarian microenvironment. The optimal finetuning of this pathway is essential for physiological processes concerning oogenesis, folliculogenesis, oocyte maturation, and embryo development. The dysregulation of PI3K/Akt can impair molecular and structural mechanisms that will lead to follicle atresia, or the inability of embryos to reach later stages of development. Due to its pivotal role in the control of cell proliferation, apoptosis, and survival mechanisms, the dysregulation of this molecular pathway can trigger the onset of pathological conditions. Among these, we will focus on diseases that can harm female fertility, such as polycystic ovary syndrome and premature ovarian failure, or women's general health, such as ovarian cancer. In this review, we report the functions of the PI3K/Akt pathway in both its physiological and pathological roles, and we address the existing application of inhibitors and activators for the balancing of the molecular cascade in ovarian pathological environments.
PubMed: 38929705
DOI: 10.3390/life14060722 -
International Journal of Molecular... Jun 2024To enhance our understanding of teleost reproductive physiology, we identified six Sichuan bream () vitellogenin genes (-) and characterized their sequence structures....
To enhance our understanding of teleost reproductive physiology, we identified six Sichuan bream () vitellogenin genes (-) and characterized their sequence structures. We categorized them into type Ⅰ (,, and ), type Ⅱ () and type Ⅲ () based on differences in their subdomain structure. The promoter sequence of has multiple estrogen response elements, and their abundance appears to correlate with the responsiveness of gene expression to estrogen. Gene expression analyses revealed that the vitellogenesis of Sichuan bream involves both heterosynthesis and autosynthesis pathways, with the dominant pathway originating from the liver. The drug treatment experiments revealed that 17β-estradiol (E) tightly regulated the level of mRNA in the liver. Feeding fish with a diet containing 100 μg/g E for three weeks significantly induced gene expression and ovarian development, leading to an earlier onset of vitellogenesis. Additionally, it was observed that the initiation of transcription required E binding to its receptor, a process primarily mediated by estrogen receptor alpha in Sichuan bream. The findings of this study provide novel insights into the molecular information of the vitellogenin gene family in teleosts, thereby contributing to the regulation of gonadal development in farmed fish.
Topics: Animals; Vitellogenins; Estrogens; Vitellogenesis; Estradiol; Promoter Regions, Genetic; Female; Fish Proteins; Phylogeny; Gene Expression Regulation; Multigene Family; Liver; Genome; Estrogen Receptor alpha
PubMed: 38928442
DOI: 10.3390/ijms25126739 -
Biomedicines May 2024Today, women's infertility is considered a social disease in females, occurring not only as an effect of POF (premature ovarian failure) but also as CTRI (cancer... (Review)
Review
Today, women's infertility is considered a social disease in females, occurring not only as an effect of POF (premature ovarian failure) but also as CTRI (cancer treatment-related infertility) in oncologic patients. Several procedures for FP (fertility preservation) are currently adopted to prevent this condition, mostly based on utilization of retrieved eggs from the patients with subsequent IVF (in vitro fertilization) or cryopreservation. However, great interest has recently been devoted to OSCs (ovarian stem cells), whose isolation from female ovaries, followed by their in vitro culture, led to their maturation to OLCs (oocyte-like cells), namely, neo-oocytes comparable to viable eggs suitable for IVF. Translation of these data to FP clinical application creates new hope in the treatment of infertility. Thus, in line with the significant progress in using stem cells in the regenerative medicine field, neo-oogenesis via OSCs, which is currently unapplicable in fertility preservation procedures, will provide novel possibilities for young and adult females in motherhood programs in the future.
PubMed: 38927346
DOI: 10.3390/biomedicines12061139 -
Diseases (Basel, Switzerland) Jun 2024Cellular metabolism, apoptosis, fertilization, and proliferation of granulosa cells belong to a battery of processes where microRNAs can be detected and associated with... (Review)
Review
Cellular metabolism, apoptosis, fertilization, and proliferation of granulosa cells belong to a battery of processes where microRNAs can be detected and associated with infertility. The aim of the present review is to focus on mammalian oocyte maturation events and the association between oocyte growth and miRNA expression. PubMed/Medline, Google Scholar and Scopus databases were searched, and 33 studies were included. Regarding the correlation among miRNA expression and the regulation of granulosa cells and cumulus cells, the most important miRNAs were let-7b, let-7c and miR-21. Additionally, the loss of Dicer, an enzyme involved in miRNA biogenesis, is probably a crucial factor in oogenesis, oocyte maturation and embryogenesis. Furthermore, miRNAs interfere with different cellular mechanisms like apoptosis, steroidogenesis, genome integrity, angiogenesis, antioxidative response and, consequently, oocyte maturation. Hence, it is of major importance to clarify the role and mechanism of each miRNA as understanding its action may develop new tools and establish new diagnostic and treatment approaches for infertility and ovarian disorders.
PubMed: 38920553
DOI: 10.3390/diseases12060121 -
BioRxiv : the Preprint Server For... Jun 2024Gametogenesis is the process by which germ cells differentiate into mature sperm and oocytes, cells essential for sexual reproduction. The sex-specific molecular...
UNLABELLED
Gametogenesis is the process by which germ cells differentiate into mature sperm and oocytes, cells essential for sexual reproduction. The sex-specific molecular programs that drive spermatogenesis and oogenesis can also serve as sex identification markers. is a research organism that has been studied in many areas of developmental biology. However investigations often disregard sex, as juveniles lack sexual dimorphism. The molecular mechanisms of gametogenesis in the segmented worm are also largely unknown. In this study, we used RNA sequencing to investigate the transcriptomic profiles of gametogenesis in juveniles. Our analysis revealed that sex-biased gene expression becomes increasingly pronounced during the advanced developmental stages, particularly during the meiotic phases of gametogenesis. We identified conserved genes associated with spermatogenesis, such as , and a novel gene , that is associated with oogenesis. Additionally, putative long non-coding RNAs were upregulated in both male and female gametogenic programs. This study provides a foundational resource for germ cell research in markers for sex identification, and offers comparative data to enhance our understanding of the evolution of gametogenesis mechanisms across species.
SUMMARY STATEMENT
This study provides insights into the mechanisms of gametogenesis in through comparative transcriptomics, unveiling sex-biased genes, including conserved and novel genes, governing this largely unexplored process.
PubMed: 38915681
DOI: 10.1101/2024.06.12.598746 -
Nature Communications Jun 2024Cytoplasmic polyadenylation plays a vital role in gametogenesis; however, the participating enzymes and substrates in mammals remain unclear. Using knockout and knock-in...
Cytoplasmic polyadenylation plays a vital role in gametogenesis; however, the participating enzymes and substrates in mammals remain unclear. Using knockout and knock-in mouse models, we describe the essential role of four TENT5 poly(A) polymerases in mouse fertility and gametogenesis. TENT5B and TENT5C play crucial yet redundant roles in oogenesis, with the double knockout of both genes leading to oocyte degeneration. Additionally, TENT5B-GFP knock-in females display a gain-of-function infertility effect, with multiple chromosomal aberrations in ovulated oocytes. TENT5C and TENT5D both regulate different stages of spermatogenesis, as shown by the sterility in males following the knockout of either gene. Finally, Tent5a knockout substantially lowers fertility, although the underlying mechanism is not directly related to gametogenesis. Through direct RNA sequencing, we discovered that TENT5s polyadenylate mRNAs encoding endoplasmic reticulum-targeted proteins essential for gametogenesis. Sequence motif analysis and reporter mRNA assays reveal that the presence of an endoplasmic reticulum-leader sequence represents the primary determinant of TENT5-mediated regulation.
Topics: Animals; Female; Male; Polyadenylation; RNA, Messenger; Mice; Mice, Knockout; Spermatogenesis; Gametogenesis; Oogenesis; Polynucleotide Adenylyltransferase; Oocytes; Fertility; Mice, Inbred C57BL
PubMed: 38909026
DOI: 10.1038/s41467-024-49479-4 -
Nature Communications Jun 2024Reproductive success relies on proper establishment and maintenance of biological sex. In many animals, including mammals, the primary gonad is initially ovary biased....
Reproductive success relies on proper establishment and maintenance of biological sex. In many animals, including mammals, the primary gonad is initially ovary biased. We previously showed the RNA binding protein (RNAbp), Rbpms2, is required for ovary fate in zebrafish. Here, we identified Rbpms2 targets in oocytes (Rbpms2-bound oocyte RNAs; rboRNAs). We identify Rbpms2 as a translational regulator of rboRNAs, which include testis factors and ribosome biogenesis factors. Further, genetic analyses indicate that Rbpms2 promotes nucleolar amplification via the mTorc1 signaling pathway, specifically through the mTorc1-activating Gap activity towards Rags 2 (Gator2) component, Missing oocyte (Mios). Cumulatively, our findings indicate that early gonocytes are in a dual poised, bipotential state in which Rbpms2 acts as a binary fate-switch. Specifically, Rbpms2 represses testis factors and promotes oocyte factors to promote oocyte progression through an essential Gator2-mediated checkpoint, thereby integrating regulation of sexual differentiation factors and nutritional availability pathways in zebrafish oogenesis.
Topics: Animals; Zebrafish; Female; Oocytes; Zebrafish Proteins; RNA-Binding Proteins; Oogenesis; Male; Ovary; Mechanistic Target of Rapamycin Complex 1; Signal Transduction; Gene Expression Regulation, Developmental; Testis; Nutrients
PubMed: 38898112
DOI: 10.1038/s41467-024-49613-2 -
BioRxiv : the Preprint Server For... Jun 2024The oocyte germline of the hermaphrodite presents a unique model to study the formation of oocytes. However, the size of the model animal and difficulties in retrieval...
The oocyte germline of the hermaphrodite presents a unique model to study the formation of oocytes. However, the size of the model animal and difficulties in retrieval of specific stages of the germline have obviated closer systematic studies of this process throughout the years. Here, we present a transcriptomic level analysis into the oogenesis of hermaphrodites. We dissected a hermaphrodite gonad into seven sections corresponding to the mitotic distal region, the pachytene, the diplotene, the early diakinesis region and the 3 most proximal oocytes, and deeply sequenced the transcriptome of each of them along with that of the fertilized egg using a single-cell RNA-seq protocol. We identified specific gene expression events as well as gene splicing events in finer detail along the oocyte germline and provided novel insights into underlying mechanisms of the oogenesis process. Furthermore, through careful review of relevant research literature coupled with patterns observed in our analysis, we attempt to delineate transcripts that may serve functions in the interaction between the germline and cells of the somatic gonad. These results expand our knowledge of the transcriptomic space of the germline and lay a foundation on which future studies of the germline can be based upon.
PubMed: 38895354
DOI: 10.1101/2024.06.03.597235 -
International Journal of Molecular... May 2024Species of the genus have served as favorite models in speciation studies; however, genetic factors of interspecific reproductive incompatibility are...
Species of the genus have served as favorite models in speciation studies; however, genetic factors of interspecific reproductive incompatibility are under-investigated. Here, we performed an analysis of hybrid female sterility by crossing females and males. Using transcriptomic data analysis and molecular, cellular, and genetic approaches, we analyzed differential gene expression, transposable element (TE) activity, piRNA biogenesis, and functional defects of oogenesis in hybrids. Premature germline stem cell loss was the most prominent defect of oogenesis in hybrid ovaries. Because of the differential expression of genes encoding piRNA pathway components, and , the functional RDC complex in hybrid ovaries was not assembled. However, the activity of the RDC complex was maintained in hybrids independent of the genomic origin of piRNA clusters. Despite the identification of a cohort of overexpressed TEs in hybrid ovaries, we found no evidence that their activity can be considered the main cause of hybrid sterility. We revealed a complicated pattern of Vasa protein expression in the hybrid germline, including partial piRNA targeting of the allele and a significant zygotic delay in expression. We arrived at the conclusion that the hybrid sterility phenotype was caused by intricate multi-locus differences between the species.
Topics: Animals; Female; Drosophila melanogaster; Male; Drosophila simulans; Drosophila Proteins; RNA, Small Interfering; DNA Transposable Elements; Ovary; Hybridization, Genetic; Oogenesis; Infertility; Crosses, Genetic; DEAD-box RNA Helicases
PubMed: 38891872
DOI: 10.3390/ijms25115681 -
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