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Centromere-specifying nucleosomes persist in aging mouse oocytes in the absence of nascent assembly.Current Biology : CB Sep 2023Centromeres direct genetic inheritance but are not themselves genetically encoded. Instead, centromeres are defined epigenetically by the presence of a histone H3...
Centromeres direct genetic inheritance but are not themselves genetically encoded. Instead, centromeres are defined epigenetically by the presence of a histone H3 variant, CENP-A. In cultured somatic cells, an established paradigm of cell-cycle-coupled propagation maintains centromere identity: CENP-A is partitioned between sisters during replication and replenished by new assembly, which is restricted to G1. The mammalian female germ line challenges this model because of the cell-cycle arrest between pre-meiotic S phase and the subsequent G1, which can last for the entire reproductive lifespan (months to decades). New CENP-A chromatin assembly maintains centromeres during prophase I in worm and starfish oocytes, suggesting that a similar process may be required for centromere inheritance in mammals. To test this hypothesis, we developed an oocyte-specific conditional knockout (cKO) mouse for Mis18α, an essential component of the assembly machinery. We find that embryos derived from Mis18α knockout oocytes fail to assemble CENP-A nucleosomes prior to zygotic genome activation (ZGA), validating the knockout model. We show that deletion of Mis18α in the female germ line at the time of birth has no impact on centromeric CENP-A nucleosome abundance, even after 6-8 months of aging. In addition, there is no detectable detriment to fertility. Thus, centromere chromatin is maintained long-term, independent of new assembly during the extended prophase I arrest in mouse oocytes.
Topics: Female; Animals; Mice; Nucleosomes; Centromere Protein A; Chromosomal Proteins, Non-Histone; Centromere; Chromatin; Oocytes; Aging; Autoantigens; Mammals
PubMed: 37582374
DOI: 10.1016/j.cub.2023.07.032 -
Science China. Life Sciences Oct 2023Sperm contributes essential paternal factors, including the paternal genome, centrosome, and oocyte-activation signals, to sexual reproduction. However, it remains...
Sperm contributes essential paternal factors, including the paternal genome, centrosome, and oocyte-activation signals, to sexual reproduction. However, it remains unresolved how sperm contributes its RNA molecules to regulate early embryonic development. Here, we show that the Caenorhabditis elegans paternal protein SPE-11 assembles into granules during meiotic divisions of spermatogenesis and later matures into a perinuclear structure where sperm RNAs localize. We reconstitute an SPE-11 liquid-phase scaffold in vitro and find that SPE-11 condensates incorporate the nematode RNA, which, in turn, promotes SPE-11 phase separation. Loss of SPE-11 does not affect sperm motility or fertilization but causes pleiotropic development defects in early embryos, and spe-11 mutant males reduce mRNA levels of genes crucial for an oocyte-to-embryo transition or embryonic development. These results reveal that SPE-11 undergoes phase separation and associates with sperm RNAs that are delivered to oocytes during fertilization, providing insights into how a paternal protein regulates early embryonic development.
Topics: Animals; Male; RNA; Semen; Sperm Motility; Spermatozoa; Spermatogenesis; Caenorhabditis elegans; Oocytes; Fertilization
PubMed: 37160652
DOI: 10.1007/s11427-022-2332-5 -
Zygote (Cambridge, England) Oct 2023One of the prominent peculiarities of nanoparticles (NPs) is their ability to cross biological barriers. Therefore, the development of NPs with different properties has... (Review)
Review
One of the prominent peculiarities of nanoparticles (NPs) is their ability to cross biological barriers. Therefore, the development of NPs with different properties has great therapeutic potential in the area of reproduction because the association of drugs, hormones and other compounds with NPs represents an alternative for delivering substances directly at a specific site and for treatment of reproductive problems. Additionally, lipid-based NPs can be taken up by the tissues of patients with ovarian failure, deep endometriosis, testicular dysfunctions, etc., opening up new perspectives for the treatment of these diseases. The development of nanomaterials with specific size, shape, ligand density and charge certainly will contribute to the next generation of therapies to solve fertility problems in humans. Therefore, this review discusses the potential of NPs to treat reproductive disorders, as well as to regulate the levels of the associated hormones. The possible limitations of the clinical use of NPs are also highlighted.
Topics: Female; Humans; Reproduction; Nanotechnology; Hormones
PubMed: 37537957
DOI: 10.1017/S0967199423000424 -
Frontiers in Genetics 2023Most epigenetic information is reprogrammed during gametogenesis and early development. However, some epigenetic information persists and can be inherited, a phenomenon...
Most epigenetic information is reprogrammed during gametogenesis and early development. However, some epigenetic information persists and can be inherited, a phenomenon that is common in plants. On the other hand, there are increasing examples of epigenetic inheritance in metazoans, especially for small non-coding RNAs. The presence of regulatory important RNAs in oocytes is undisputed, whereas the corresponding RNA payload in spermatozoa and its regulatory influence in the zygote and early embryogenesis is largely enigmatic. For humans, we herein describe small YRNA fragments (YsRNA) as a paternal contribution to the zygote. First, we trace the biogenesis of these YsRNAs from the source YRNAs with respect to the 5' and 3' modifications. Both the length and modifications make these YsRNAs reminiscent of canonical piRNAs that are not derived from piRNA clusters. Second, from the early stages of spermatogenesis to maturation in the epididymis, we observe distinct YsRNA profile dynamics in the male germline. We detected YsRNAs exclusively in mature sperm heads, the precursor of the male pronucleus in the zygote, suggesting an important role of the epididymis as a site for transmitting and modification of epigenetic information in the form of YsRNA between soma and germline in humans. Since this YsRNA-based epigenetic mechanism is effective across generations, we wondered whether this phenomenon of epigenetic inheritance has an adaptive value. Full-length YRNAs bind to Ro60, an RNA chaperone that additionally binds to non-coding RNAs. We described the profiles of non-coding RNAs bound to Ro60 in the human sperm head and detected specific binding profiles of RNA to Ro60 but no YRNA bound to Ro60. We hypothesize that the sperm head Ro60 system is functional. An adaptive phenotype mediated by the presence of a large amount of YsRNA in the sperm head, and thus as a paternal contribution in the zygote, might be related to an association of YsRNA with YRNA that prevents the adoption of a YRNA secondary structure capable of binding to Ro60. We hypothesize that preventing YRNAs from acting as Ro60-associated gatekeepers for misfolded RNAs in the zygote and early development may enhance RNA chaperoning and, thus, represent the adaptive molecular phenotype.
PubMed: 38162679
DOI: 10.3389/fgene.2023.1294389 -
Zygote (Cambridge, England) Dec 2023Kisspeptin is characterized as a neuropeptide with a pivotal function in female and male infertility, and its antioxidant properties have been demonstrated. In this...
Kisspeptin is characterized as a neuropeptide with a pivotal function in female and male infertility, and its antioxidant properties have been demonstrated. In this study, the effects of kisspeptin on the improvement of the vitrification and thawing results of human ovarian tissues were investigated. In this work, 12 ovaries from patients who underwent hysterectomy were collected laparoscopically, and then 32 samples from each of their tissues were taken. Haematoxylin and eosin (H&E) staining was performed to check the normality of the ovarian tissue and, subsequently, the samples were allocated randomly into four groups, including: (1) fresh (control), (2) vitrification, (3) vitrified + 1 μM kisspeptin, and (4) vitrified + 10 μM kisspeptin groups. After vitrification, thawing, and tissue culture processes, H&E staining for tissue quality assessment, terminal deoxynucleotidyl transferase dUTP nick end labelling assay for apoptosis evaluation, and malondialdehyde (MDA), superoxide dismutase (SOD), and ferric reducing ability of plasma tests for oxidative stress appraisal were carried out. Our histological results showed incoherency of ovarian tissue morphology in the vitrification group compared with other groups. Other findings implicated increased apoptosis rate and MDA concentration and reduced SOD activity and total antioxidant capacity (TAC) in the vitrification group compared with the control group ( < 0.05). Moreover, decreased apoptosis rate and MDA concentration, and increased TAC and SOD function were observed in the vitrification with kisspeptin groups (1 μM and 10 μM) compared with the vitrified group ( < 0.05). Our reports express that kisspeptin is an effective agent to overcome the negative effects of vitrification by regulating reactive oxygen species-related apoptotic processes.
Topics: Humans; Male; Female; Vitrification; Ovary; Cryopreservation; Kisspeptins; Reactive Oxygen Species; Antioxidants; Superoxide Dismutase
PubMed: 37655529
DOI: 10.1017/S0967199423000412 -
Zygote (Cambridge, England) Dec 2023Our objective was to study whether serum anti-Müllerian hormone (AMH) concentrations were associated with embryo morphokinetic events. This retrospective cohort study...
Our objective was to study whether serum anti-Müllerian hormone (AMH) concentrations were associated with embryo morphokinetic events. This retrospective cohort study was performed in a private university-affiliated fertilization centre between March 2019 and December 2020 and included 902 oocytes cultured in a time-lapse imaging incubator, obtained from 114 intracytoplasmic sperm injection cycles performed. The relationship between AMH concentrations and morphokinetic events was investigated by considering the clustering of data (multiple embryos/patient). Evaluated kinetic markers were time to pronuclei appearance (tPNa) and fading (tPNf), time to two (t2), three (t3), four (t4), five (t5), six (t6), seven (t7), and eight cells (t8), (tSB) and time to the start of blastulation (tSB) and to blastulation (tB). Significant inverse relationships were observed between serum AMH concentrations and tPNf, t3, t4, t5, t6, t7, t8, and tB. The AMH was positively correlated with the KIDScore and implantation rate. Increased serum AMH concentrations correlated with faster embryo development. The clinical implications of this effect on embryo development warrant further investigation.
Topics: Humans; Male; Anti-Mullerian Hormone; Retrospective Studies; Blastocyst; Time-Lapse Imaging; Semen; Embryonic Development; Fertilization in Vitro; Embryo Culture Techniques
PubMed: 37743564
DOI: 10.1017/S0967199423000370 -
Life Science Alliance Aug 2023Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is a protein essential for the maintenance of DNA methylation in somatic cells. However, UHRF1 is predominantly...
Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is a protein essential for the maintenance of DNA methylation in somatic cells. However, UHRF1 is predominantly localized in the cytoplasm of mouse oocytes and preimplantation embryos, where it may play a role unrelated to the nuclear function. We herein report that oocyte-specific KO results in impaired chromosome segregation, abnormal cleavage division, and preimplantation lethality of derived embryos. Our nuclear transfer experiment showed that the phenotype is attributable to cytoplasmic rather than nuclear defects of the zygotes. A proteomic analysis of KO oocytes revealed the down-regulation of proteins associated with microtubules including tubulins, which occurred independently of transcriptomic changes. Intriguingly, cytoplasmic lattices were disorganized, and mitochondria, endoplasmic reticulum, and components of the subcortical maternal complex were mislocalized. Thus, maternal UHRF1 regulates the proper cytoplasmic architecture and function of oocytes and preimplantation embryos, likely through a mechanism unrelated to DNA methylation.
Topics: Animals; Mice; Proteomics; Oocytes; Cytosol; Endoplasmic Reticulum; Mitochondria; CCAAT-Enhancer-Binding Proteins; Ubiquitin-Protein Ligases
PubMed: 37225425
DOI: 10.26508/lsa.202301904 -
Zygote (Cambridge, England) Apr 2024Men with diabetes frequently experience spermatogenic dysfunction, which is the most significant sign that diabetes has harmed their ability to reproduce. The effect of...
Men with diabetes frequently experience spermatogenic dysfunction, which is the most significant sign that diabetes has harmed their ability to reproduce. The effect of various doses of the hydro-alcoholic extract of leaves on the pituitary-gonadal axis, sperm motility and number, antioxidant system, changes in testicular tissue structure, and spermatogenesis in healthy and diabetic rats has been examined in the current study. Eighty male rats that had been streptozotocin-induced diabetic and healthy were divided into eight groups: (1) control, (2) (50 mg/kg), (3) (100 mg/kg), (4) (200 mg/kg), (5) DM (6) DM+ (50 mg/kg), (7) DM+ (100 mg/kg) and (8) DM+ (200 mg/kg) and were administered orally for 48 days consecutive. Following the studies, analysis of the testicular tissues' antioxidant capacity as well as sperm parameters, Johnsen's scoring and morphometric evaluation, histology, biochemical and stereology studies were performed.The outcomes showed that 50 and 100 mg/kg considerably enhanced the testicular morphology, sperm parameters, and reproductive organs to varying degrees in diabetic rats. After 50 mg/kg administration, glutathione peroxidase (GPX) and catalase (CAT) levels in the testicular tissue were increased whereas malondialdehyde (MDA) levels were markedly decreased. may help protect against diabetic-induced spermatogenic dysfunction in male rats by enhancing the activities of antioxidant enzymes in lower dosages.
Topics: Animals; Male; Diabetes Mellitus, Experimental; Spermatogenesis; Plant Extracts; Testis; Nerium; Rats; Antioxidants; Spermatozoa; Sperm Motility; Glutathione Peroxidase; Streptozocin; Catalase; Plant Leaves; Rats, Wistar; Malondialdehyde
PubMed: 38284273
DOI: 10.1017/S0967199423000643 -
International Journal of Molecular... Jul 2023Zinc finger and SCAN domain-containing 4 (), a DNA-binding protein, maintains telomere length and plays a key role in critical aspects of mouse embryonic stem cells,...
Zinc finger and SCAN domain-containing 4 (), a DNA-binding protein, maintains telomere length and plays a key role in critical aspects of mouse embryonic stem cells, including maintaining genomic stability and defying cellular senescence. However, the effect of in porcine parthenogenetic embryos remains unclear. To investigate the function of and the underlying mechanism in porcine embryo development, was knocked down via dsRNA injection in the one-cell stage. was highly expressed in the four- and five- to eight-cell stages in porcine embryos. The percentage of four-cell stage embryos, five- to eight-cell stage embryos, and blastocysts was lower in the knockdown group than in the control group. Notably, depletion of induced the protein expression of and 5-Methylcytosine (5mC, a methylated form of the DNA base cytosine) in the four-cell stage. The H3K27ac level and ZGA genes expression decreased following knockdown. Furthermore, knockdown led to DNA damage and shortened telomere compared with the control. Additionally, -dsRNA was injected to reduce DNA hypermethylation in knockdown embryos. knockdown rescued telomere shortening and developmental defects caused by knockdown. In conclusion, is involved in the regulation of transcriptional activity and is essential for maintaining telomere length by regulating expression in porcine ZGA.
Topics: Animals; Mice; Swine; Transcription Factors; Telomere; Telomere Shortening; DNA-Binding Proteins; Zygote; Embryonic Development; Gene Expression Regulation, Developmental
PubMed: 37569497
DOI: 10.3390/ijms241512121 -
Genome Research Aug 2023Cys2-His2 zinc finger genes (ZNFs) form the largest family of transcription factors in metazoans. ZNF evolution is highly dynamic and characterized by the rapid...
Cys2-His2 zinc finger genes (ZNFs) form the largest family of transcription factors in metazoans. ZNF evolution is highly dynamic and characterized by the rapid expansion and contraction of numerous subfamilies across the animal phylogeny. The forces and mechanisms underlying rapid ZNF evolution remain poorly understood, but there is growing evidence that, in tetrapods, the targeting and repression of lineage-specific transposable elements (TEs) plays a critical role in the evolution of the Krüppel-associated box ZNF (KZNF) subfamily. Currently, it is unknown whether this function and coevolutionary relationship is unique to KZNFs or is a broader feature of metazoan ZNFs. Here, we present evidence that genomic conflict with TEs has been a central driver of the diversification of ZNFs in animals. Sampling from 3221 genome assemblies, we show that the copy number of retroelements correlates with that of ZNFs across at least 750 million years of metazoan evolution. Using computational predictions, we show that ZNFs preferentially bind TEs in diverse animal species. We further investigate the largest ZNF subfamily found in cyprinid fish, which is characterized by a conserved sequence we dubbed the fish N-terminal zinc finger-associated (FiNZ) domain. Zebrafish possess approximately 700 FiNZ-ZNFs, many of which are evolving adaptively under positive selection. Like mammalian KZNFs, most zebrafish FiNZ-ZNFs are expressed at the onset of zygotic genome activation, and blocking their translation using morpholinos during early embryogenesis results in derepression of transcriptionally active TEs. Together, these data suggest that ZNF diversification has been intimately connected to TE expansion throughout animal evolution.
Topics: Animals; DNA Transposable Elements; Zebrafish; Zinc Fingers; Transcription Factors; Mammals; Evolution, Molecular
PubMed: 37714714
DOI: 10.1101/gr.277966.123