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Nature Communications Feb 2024Mitochondria are inherited exclusively from the mothers and are required for the proper development of embryos. Hence, germline mitochondrial quality is highly regulated...
Mitochondria are inherited exclusively from the mothers and are required for the proper development of embryos. Hence, germline mitochondrial quality is highly regulated during oogenesis to ensure oocyte viability. How nutrient availability influences germline mitochondrial quality control is unclear. Here we find that fasting leads to the accumulation of mitochondrial clumps and oogenesis arrest in Drosophila. Fasting induces the downregulation of the DIP1-Clueless pathway, leading to an increase in the expression of a stable intronic sequence RNA called sisR-1. Mechanistically, sisR-1 localizes to the mitochondrial clumps to inhibit the poly-ubiquitination of the outer mitochondrial protein Porin/VDAC1, thereby suppressing p62-mediated mitophagy. Alleviation of the fasting-induced high sisR-1 levels by either sisR-1 RNAi or refeeding leads to mitophagy, the resumption of oogenesis and an improvement in oocyte quality. Thus, our study provides a possible mechanism by which fasting can improve oocyte quality by modulating the mitochondrial quality control pathway. Of note, we uncover that the sisR-1 response also regulates mitochondrial clumping and oogenesis during protein deprivation, heat shock and aging, suggesting a broader role for this mechanism in germline mitochondrial quality control.
Topics: Animals; Introns; Mitochondria; Oocytes; Drosophila; Nutrients
PubMed: 38341415
DOI: 10.1038/s41467-024-45651-y -
International Journal of Molecular... Jan 2024Ovarian tissue cryopreservation is gaining importance as a successful method to restore fertility to girls and young women at high risk of sterility. However, there are... (Review)
Review
Ovarian tissue cryopreservation is gaining importance as a successful method to restore fertility to girls and young women at high risk of sterility. However, there are concerns regarding the safety of transplantation after ovarian tissue cryopreservation due to the high risk of reintroducing cancer cells and causing disease recurrence. In these cases, the development of culture systems that support oocyte development from the primordial follicle stage is required. Notable achievements have been reached in human follicle in vitro growth in the past decade. Currently, systems for the in vitro culture of ovarian tissue are based on two-dimensional substrates that do not support the survival of follicles or recapitulate the mechanical heterogenicity in the mammalian ovary. Recognition of the importance of special arrangements between cells has spurred research in three-dimensional culture systems, and the provision of a precise culture system that maximizes the diffusion of nutrients and gases through the follicles has raised interest in advanced biomimetic models. The current review critically examines various culture systems employed for the in vitro development of follicles, with a particular focus on solutions utilizing Organ-on-a-Chip (OOC) technology. The emphasis on OOC technology underscores its role as a promising avenue in ensuring the successful cultivation and maintenance of follicular structures during the culture period.
Topics: Animals; Humans; Female; Ovary; Ovarian Follicle; Cryopreservation; Oogenesis; Mammals
PubMed: 38338788
DOI: 10.3390/ijms25031510 -
Animals : An Open Access Journal From... Feb 2024Zygote arrest-1 (Zar1) and Wilms' tumor 1 (Wt1) play an important role in oogenesis, with the latter also involved in testicular development and gender differentiation....
Zygote arrest-1 (Zar1) and Wilms' tumor 1 (Wt1) play an important role in oogenesis, with the latter also involved in testicular development and gender differentiation. Here, and were identified in Asian seabass (), a hermaphrodite fish, as the valuable model for studying sex differentiation. The cloned cDNA fragments of were 1192 bp, encoding 336 amino acids, and contained a zinc-binding domain, while those of cDNA were 1521 bp, encoding a peptide of 423 amino acids with a Zn finger domain belonging to Wt1b family. RT-qPCR analysis showed that mRNA was exclusively expressed in the ovary, while mRNA was majorly expressed in the gonads in a higher amount in the testis than in the ovary. In situ hybridization results showed that mRNA was mainly concentrated in oogonia and oocytes at early stages in the ovary, but were undetectable in the testis. mRNA was localized not only in gonadal somatic cells (the testis and ovary), but also in female and male germ cells in the early developmental stages, such as those of previtellogenic oocytes, spermatogonia, spermatocytes and spermatids. These results indicated that and possibly play roles in gonadal development. Therefore, the findings of this study will provide a basis for clarifying the mechanism of and in regulating germ cell development and the sex reversal of Asian seabass and even other hermaphroditic species.
PubMed: 38338151
DOI: 10.3390/ani14030508 -
BioRxiv : the Preprint Server For... Jan 2024Reproductive success relies on proper establishment and maintenance of biological sex. In many animals, including mammals, the primary gonad is initially ovary in...
Reproductive success relies on proper establishment and maintenance of biological sex. In many animals, including mammals, the primary gonad is initially ovary in character. We previously showed the RNA binding protein (RNAbp), Rbpms2, is required for ovary fate in zebrafish. Here, we identified Rbpms2 targets in oocytes ). We identify Rbpms2 as a translational regulator of , 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.
PubMed: 38328218
DOI: 10.1101/2024.01.25.577235 -
Genetics Research 2024Tesmin, a 60 kDa protein encoded by the metallothionein-like 5 (MTL5) gene, plays a vital role in spermatogenesis and oogenesis. Recent research has unveiled its...
BACKGROUND
Tesmin, a 60 kDa protein encoded by the metallothionein-like 5 (MTL5) gene, plays a vital role in spermatogenesis and oogenesis. Recent research has unveiled its potential involvement in malignancies, although its impact on HCC remains poorly understood.
METHODS
In this study, we sought to elucidate the clinical significance of tesmin in HCC patients. We investigated the relationship between tesmin expression and the prognosis of individuals with hepatocellular carcinoma (HCC), as well as its potential role in tumor proliferation and invasion. Immunohistochemistry (IHC) was employed to assess the expression of tesmin in HCC tissues. Chi-square tests were conducted to analyze the correlation between tesmin expression and various clinicopathological features among HCC patients. For survival analysis, we employed the Kaplan-Meier method and conducted Cox regression analyses. To investigate the functional role of tesmin, we utilized shRNA constructs for transfection-mediated knockdown. Proliferation was assessed using the CCK-8 assay, and invasive capability was determined through Matrigel Transwell assays.
RESULTS
IHC results indicated that tesmin expression was prominently observed in cancerous tissue. Notably, we observed a significant association between tesmin expression and tumor stage and invasion in HCC patients from both our medical center and TCGA dataset. Survival analysis further revealed that tesmin expression emerged as an independent prognostic factor for overall survival among individuals with HCC. Furthermore, cellular experiments demonstrated that knockdown of tesmin led to decreased proliferation and invasion of HCC cells.
CONCLUSIONS
Our findings suggest that tesmin may serve as a novel prognostic marker for HCC, highlighting its potential as a target for further research into HCC treatment. Additionally, the functional experiments support the notion that tesmin may participate in promoting the proliferation and invasion of HCC cells, warranting further investigations into its mechanistic involvement in HCC progression.
Topics: Humans; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cell Line, Tumor; Clinical Relevance; Liver Neoplasms; Metallothionein; Prognosis
PubMed: 38283987
DOI: 10.1155/2024/3058875 -
Journal of Insect Physiology Mar 2024The environment is changing faster than anticipated due to climate change, making species more vulnerable to its impacts. The level of vulnerability of species is...
The environment is changing faster than anticipated due to climate change, making species more vulnerable to its impacts. The level of vulnerability of species is influenced by factors such as the degree and duration of exposure, as well as the physiological sensitivity of organisms to changes in their environments, which has been shown to vary among species, populations, and individuals. Here, we compared physiological changes in fecundity, critical thermalmaximum (CT), respiratory quotient (RQ), and DNA damage in ovaries in response to temperature stress in two species of fruit fly, Drosophila melanogaster (25 vs. 29.5 °C) and Drosophila pseudoobscura (20.5 vs. 25 °C). The fecundity of D. melanogaster was more affected by high temperatures when exposed during egg through adult development, while D. pseudoobscura was most significantly affected when exposed to high temperatures exclusively during egg through pupal development. Additionally, D. melanogaster males exhibited a decrease of CT under high temperatures, while females showed an increase of CT when exposed to high temperatures during egg through adult development. while D. pseudoobscura females and males showed an increased CT only when reared at high temperatures during egg through pupae development. Moreover, both species showed an acceleration in oogenesis and an increase in apoptosis due to heat stress. These changes can likely be attributed to key differences in the geographic range, thermal range, development time, and other different factors between these two systems. Through this comparison of variation in physiology and developmental response to thermal stress, we found important differences between species and sexes that suggest future work needs to account for these factors separately in understanding the effects of constant increased temperatures.
Topics: Humans; Male; Female; Animals; Drosophila melanogaster; Drosophila; Temperature; Fertility; Heat-Shock Response
PubMed: 38278288
DOI: 10.1016/j.jinsphys.2024.104616 -
Life (Basel, Switzerland) Dec 2023The chromatin-remodeling protein ATRX, which is currently recognized as one of the key genome caretakers, plays an important role in oogenesis and early embryogenesis in...
The chromatin-remodeling protein ATRX, which is currently recognized as one of the key genome caretakers, plays an important role in oogenesis and early embryogenesis in mammals. ATRX distribution in the nuclei of mouse embryos developing in vivo and in vitro, including when the embryos are arrested at the two-cell stage-the so-called two-cell block in vitro-was studied using immunofluorescent labeling and FISH. In normally developing two- and four-cell embryos, ATRX was found to be closely colocalized with pericentromeric DNA sequences detected with a probe to the mouse major satellite DNA. The association of ATRX with pericentromeric heterochromatin is mediated by nuclear actin and reduced after the treatment of embryos with latrunculin B. When culturing embryos in vitro, the distribution pattern of ATRX changes, leading to a decrease in the association of this protein with major satellite DNA especially under the two-cell block in vitro. Taken together, our data suggest that the intranuclear distribution of ATRX reflects the viability of mouse embryos and their probability of successful preimplantation development.
PubMed: 38276254
DOI: 10.3390/life14010005 -
Cells Jan 2024Oogenesis is a developmental process leading to the formation of an oocyte, a haploid gamete, which upon fertilisation and sperm entry allows the male and the female... (Review)
Review
Oogenesis is a developmental process leading to the formation of an oocyte, a haploid gamete, which upon fertilisation and sperm entry allows the male and the female pronuclei to fuse and give rise to a zygote. In addition to forming a haploid gamete, oogenesis builds up a store of proteins, mRNAs, and organelles in the oocyte needed for the development of the future embryo. In several species, such as , the polarity axes determinants of the future embryo must be asymmetrically distributed prior to fertilisation. In the oocyte, the correct positioning of the nucleus is essential for establishing the dorsoventral polarity axis of the future embryo and allowing the meiotic spindles to be positioned in close vicinity to the unique sperm entry point into the oocyte.
Topics: Animals; Male; Female; Drosophila; Semen; Oogenesis; Oocytes; Cell Nucleus
PubMed: 38275826
DOI: 10.3390/cells13020201 -
International Journal of Molecular... Jan 2024The development of the ovarian antral follicle is a complex, highly regulated process. Oocytes orchestrate and coordinate the development of mammalian ovarian follicles,...
The development of the ovarian antral follicle is a complex, highly regulated process. Oocytes orchestrate and coordinate the development of mammalian ovarian follicles, and the rate of follicular development is governed by a developmental program intrinsic to the oocyte. Characterizing oocyte signatures during this dynamic process is critical for understanding oocyte maturation and follicular development. Although the transcriptional signature of sheep oocytes matured in vitro and preovulatory oocytes have been previously described, the transcriptional changes of oocytes in antral follicles have not. Here, we used single-cell transcriptomics (SmartSeq2) to characterize sheep oocytes from small, medium, and large antral follicles. We characterized the transcriptomic landscape of sheep oocytes during antral follicle development, identifying unique features in the transcriptional atlas, stage-specific molecular signatures, oocyte-secreted factors, and transcription factor networks. Notably, we identified the specific expression of 222 genes in the LO, 8 and 6 genes that were stage-specific in the MO and SO, respectively. We also elucidated signaling pathways in each antral follicle size that may reflect oocyte quality and in vitro maturation competency. Additionally, we discovered key biological processes that drive the transition from small to large antral follicles, revealing hub genes involved in follicle recruitment and selection. Thus, our work provides a comprehensive characterization of the single-oocyte transcriptome, filling a gap in the mapping of the molecular landscape of sheep oogenesis. We also provide key insights into the transcriptional regulation of the critical sizes of antral follicular development, which is essential for understanding how the oocyte orchestrates follicular development.
Topics: Female; Animals; Sheep; Single-Cell Gene Expression Analysis; Oocytes; Ovarian Follicle; Oogenesis; Ovary; Mammals; Carbamates; Organometallic Compounds
PubMed: 38255985
DOI: 10.3390/ijms25020910 -
Antioxidants (Basel, Switzerland) Dec 2023Vitamin B12 is an essential cofactor involved in the function of two enzymes: cytosolic methionine synthase and mitochondrial methylmalonic-CoA mutase. In our previous...
Vitamin B12 is an essential cofactor involved in the function of two enzymes: cytosolic methionine synthase and mitochondrial methylmalonic-CoA mutase. In our previous studies, caffeine (1,3,7-trimethylxanthine), the most popular bioactivator, was shown to reduce yolk protein (vitellogenin) and fertility in a model. Based on the previous finding that methionine supplementation increases vitellogenesis in , we investigated the role of vitamin B12 in methionine-mediated vitellogenesis during oogenesis in caffeine-ingested animals (CIA). Vitamin B12 supplementation improved vitellogenesis and reduced oxidative stress by decreasing mitochondrial function in CIA. Furthermore, the decreased number of developing oocytes and high levels of reactive oxygen species in oocytes from CIA were recovered with vitamin B12 supplementation through a reduction in mitochondrial stress, which increased vitellogenesis. Taken together, vitamin B12 supplementation can reverse the negative effects of caffeine intake by enhancing methionine-mediated vitellogenesis and oocyte development by reducing mitochondrial stress.
PubMed: 38247478
DOI: 10.3390/antiox13010053