Biology subjects

Ogura, A.

Publications and source records attributed to Ogura, A..

9 recordsLinked to original sources

bioRxiv2026

Initiating mammalian reproduction from a single male genome

Sex in mammals is unidirectionally determined by the configuration of sex chromosomes. In contrast, several species, including fishes, can switch sexes in response to environmental cues, illustrating the reproductive advantages of sexual plasticity. Thus, technologies that can bypass the unidirectional nature of mammalian sex determination could open new avenues in reproductive biology. Here, by establishing a method that enables robust Y-chromosome elimination in embryos, we provide a strategy to regulate sex in mice. We show that this approach efficiently induces male-to-female sex reversal by releasing the Y chromosome as micronuclei during early development. When integrated with optimized somatic cell nuclear transfer, it enabled the parallel production of both male and sex-reversed female mice from a single male genome source. Offspring were successfully obtained from crosses between these male and sex-reversed female clones, demonstrating that this "dual-sex cloning" strategy can initiate sexual reproduction solely from a male somatic genome. These findings highlight dual-sex cloning as a valuable platform for securing mammalian reproduction and biodiversity from limited genetic resources.

developmental biology↗

bioRxiv2026

Repetitive sequence material shapes the earliest stages of de novo gene evolution in insects

A fundamental unresolved question in molecular evolution is how novel genes arise from noncoding DNA and become fixed within stable gene repertoires. Here, we performed comparative genomic analyses across evolutionary timescales in insects using chromosome-scale genome assemblies of two cricket species, Teleogryllus occipitalis and Tarbinskiellus portentosus. Using conservative criteria, we identified 41 de novo gene candidates derived from intergenic regions in the Te. occipitalis lineage. These genes are simple and compact, exhibit hallmarks of evolutionarily young genes, and frequently contain fragments of transposable elements and simple sequence repeats. Across insects, such repetitive sequence fragments show positional homology but lack sequence conservation in older genes, suggesting that they serve as sequence material for gene emergence during early stages of gene evolution. In contrast, insertions after gene establishment are strongly constrained. We propose a model in which stages of gene evolution are characterized by shifts in selective pressure on the incorporation of sequence material.

evolutionary biology↗

bioRxiv2025

Resf1 is required for proper placental development and configuration of trophoblast cell-specific heterochromatin

Resf1 (Retroelement silencing factor 1) is involved in retroelement silencing cooperated with H3K9 methyltransferase SETDB1 by regulating H3K9 methylation in mouse embryonic stem cells (mESCs). However, it remains unknown whether Resf1 functions in retroelement silencing in vivo, and has a role in development. Here, we established Resf1-deficient mice, which exhibited developmental delay, partial embryonic lethality, and placental defects. Notably, retroelements were also upregulated in the Resf1-deficient placenta, correlating with increased expression of nearby genes. To further assess whether Resf1 functions within the trophoblast lineage, we generated Resf1-deficient trophoblast stem cell (TSC) lines. Both undifferentiated TSCs and differentiated TSCs (D-TSCs) display increased retroelement expression along with elevated levels of genes associated with placental development. Moreover, Resf1-deficient TSCs exhibit compromised maintenance of H3K9me3 domains in a manner independent of SETDB1. Collectively, our findings reveal that Resf1 plays multifaceted roles beyond retroelement silencing, underscoring its importance in development and its critical function in trophoblast lineage regulation.

developmental biology↗

bioRxiv2024

The oocyte zinc transporter Slc39a10/Zip10 is a regulator of zinc sparks during fertilization in mice.

In all vertebrates studied to date, a rise(s) in intracellular calcium is indispensable for successful fertilization and further embryonic development. Recent studies demonstrated that zinc is ejected to the extracellular milieu, the zinc spark, and follows the first few calcium rises of fertilization. However, the role of the zinc sparks in fertilization and development, and the supporting influx mechanism(s) are unknown. In this study, we focused on zinc transporters Zip10/Slc39a10 which was expressed in mouse oocytes through follicular development, and investigated the oocyte-specific deficient mice for Zip10 (Zip10d/d: Zip10flox/flox Gdf9Cre/+). Zip10 mRNA or ZIP10 protein was expressed throughout folliculogenesis in the oocyte or plasma membrane, respectively. The number of ovulated oocytes was examined in Zip10d/d mice, and no change from the number of oocytes was observed. Zip10d/d oocytes decreased zinc level in the oocytes, but did not affect maturation and metaphase II spindles formation. Fertilization-induced calcium oscillations were present in Zip10d/d oocytes, but zinc sparks were not observed. Despite other events of egg activation proceeding normally in Zip10d/doocytes, embryo development into 4-cells and beyond was compromised. We show here for the first time that the zinc transporter ZIP10 contributes to zinc homeostasis in oocytes and embryos, highlighting the role of labile zinc ions in early development. Submission informationThe zinc transporter, Slc39a10/Zip10, is required for the zinc sparks of fertilization in mice.

developmental biology↗

bioRxiv2022

OVGP1 is an oviductal fluid factor essential particularly for early embryonic development in golden hamsters

The mammalian oviductal lumen is a specialized chamber that provides an environment that strictly regulates fertilization an early embryogenesis, the regulatory mechanisms to gametes/zygote are still largely unknown. In this report, we studied the oviductal regulation of early embryonic development using Ovgp1 (a gene encoding an oviductal humoral factor, OVGP1)-knockout (KO) hamsters. The experimental results revealed the following: 1) Female Ovgp1-KO hamsters fail to produce any litters at all; 2) In the oviducts from KO animal, fertilized eggs are sometimes identified, but their morphology shows abnormal features; 3) The number of implantations in the KO females is evidently low; 4) Even if implantations occur, the embryos develop abnormally and eventually become embryonic lethal; and 5) Ovgp1-KO females transferred to wild-type females produce KO egg-derived litters, but the reverse experiment does not. These results suggest that OVGP1-mediated physiological events are crucial for early embryonic development in vivo. This animal model shows that the fate of the fertilized egg is not only genetically determined, but that the surrounding oviductal microenvironment plays a pivotal role in normal embryonic development. Summary statementDeficiency an oviductal humoral factor (OVGP1) caused female infertility in the golden hamsters. The presence or absence of OVGP1 has significant physiological effects on early embryonic development in vivo.

developmental biology↗

bioRxiv2022

Toxicity of House Cricket (Acheta domesticus) in Mice

There is an urgent need to address the shortage of animal protein due to food shortages caused by the global population growth. Crickets contain an abundance of proteins in their exoskeleton and muscles and have attracted attention as a new protein source; however, their safety as a food source has not been confirmed. We evaluated the toxicity of the House cricket (Acheta domesticus), on cells and mammals. In genotoxicity in vitro, cricket powder was added to Chinese hamster lung CHL-IU cells at concentrations of 5,000 {micro}g/mL, and the rate of chromosomal aberrations was assessed. In genotoxicity in vivo, mice were orally administered up to 2,000 mg/kg of cricket powder for 2 days. In both tests, cricket powder did not show any toxic effect. A repeated oral toxicity study was performed administering up to 3,000 mg/kg of cricket powder or control (saline) for 14 or 90 consecutive days and measuring body weight changes, blood biochemistry, blood properties, and organ weights. In each time course, there were no differences in there parameters between the control and cricket powder treated groups. These results suggest that House crickets ([≤]3,000 mg/kg) are not toxic to cells and organisms.

pharmacology and toxicology↗

bioRxiv2021

Production of offspring from azoospermic mice with meiotic failure: Precise biparental meiosis within halved oocytes

While the large volume of mammalian oocytes is necessary for embryo development, it can lead to error-prone chromosomal segregation during meiosis. Conversely, we hypothesized that smaller oocytes would have a great unidentified potential to stabilize unstable meiosis and improve the development of the resultant embryos. Here, we show that reducing ooplasmic volume can rescue highly error-prone fertilization using primary spermatocytes by preventing segregation errors of chromosomes during biparental meiosis. High-resolution live-imaging analysis revealed that erroneous chromosome segregation occurred in most (90%) spermatocyte-injected oocytes of normal size, but could be ameliorated to 40% in halved oocytes. The birth rate improved remarkably from 1% to 19% (P < 0.0001). Importantly, this technique enabled the production of offspring from azoospermic mice with spermatocyte arrest caused by STX2 deficiency, an azoospermia factor also found in humans. Thus, contrary to popular opinion, oocytes inherently have a strong potential for precise meiotic divisions, which can be evoked by reduction of the ooplasmic volume. Their potential might help rescue cases of untreatable human azoospermia with spermatocyte arrest.

developmental biology↗

bioRxiv2021

Golden hamster piRNAs are necessary for early embryonic development and establishment of spermatogonia

PIWI-associated RNAs (piRNAs) support the germline by suppressing retrotransposons and genes. In mice, piRNAs are essential for spermatogenesis but not oogenesis. To test how this applies to other mammals, we deleted Mov10l1 helicase in golden hamster, whose piRNA pathway is configured more similarly to that of other mammals. Mov10l1-/- male hamsters showed impaired establishment of spermatogonia accompanied by transcriptome dysregulation and a surge in MYSERV retrotransposon expression. The rare viable spermatogenic cells showed a meiotic failure phenotype like Mov10l1-/- mice. Female Mov10l1-/- hamsters were sterile due to post-meiotic loss of developmental competence in zygotes. Unique phenotypes of Mov10l1-/- hamsters demonstrate the adaptive nature of piRNA-mediated control of genes and retrotransposons in order to confront emerging genomic threats or acquire new physiological roles.

molecular biology↗

bioRxiv2019

A non-mosaic humanized mouse model of Down syndrome, trisomy of the long arm of human chromosome 21 in mouse chromosome background

Down syndrome (DS) is a complex human condition, and animal models trisomic for human chromosome 21 (HSA21) genes or orthologs provide insights into better understanding and treating DS. However, HSA21 orthologs are distributed into three mouse chromosomes, preventing us from generating mouse models trisomy of a complete set of HSA21 orthologs. The only existing humanized mouse DS model, Tc1, carries a HSA21 with over 20% of protein coding genes (PCGs) disrupted. More importantly, due to the human centromere, Tc1 is mosaic (a mix of euploid and trisomic cells), which makes every mouse unique and compromises interpretation of results. Here, we used mouse artificial chromosome (MAC) technology to "clone" the 34 MB long arm of HSA21 (HSA21q). Through multiple steps of microcell-mediated chromosome transfer we created a new humanized DS mouse model, Tc(HSA21q;MAC)1Yakaz ("TcMAC21"). Constitutive EGFP expression from the transchromosome and fluorescent in situ hybridization validate that TcMAC21, containing a hybrid chromosome of HSA21q and mouse centromere, is not mosaic. Whole genome sequencing shows that TcMAC21 contains a nearly complete copy of HSA21q with 93% of intact PCGs, while RNA-seq and additional mRNA/protein expression analyses confirm that PCGs are transcribed and regulated. A battery of tests show that TcMAC21 recapitulates many DS phenotypes including morphological anomalies in heart, craniofacial skeleton and brain, pathologies at molecular and cellular level, and impairments in learning, memory and synaptic plasticity. TcMAC21 is the most complete mouse model of DS extant and has potential for supporting a wide range of basic and preclinical research. Significance StatementIn the last 25 years, mouse models of trisomy 21 have supported research into Down syndrome, from defining the basis for developmental effects up to support for clinical trials. However, existing models have significant shortfalls, especially for preclinical studies. These deficiencies include incomplete or inappropriate representation of trisomic genes, absence of an extra chromosome, and mosaicism. Using cutting edge technologies we produced a mouse artificial chromosome containing the entire 34Mb long arm of human chromosome 21 and, with assisted reproductive technologies, established it in the germ line of mice. This trisomic mouse manifests developmental and functional features of Down syndrome, including hippocampal-based learning and memory deficits. This is the most complete model of Down syndrome produced to date.

genetics↗