Biology subjects

Hondo, E.

Publications and source records attributed to Hondo, E..

12 recordsLinked to original sources

bioRxiv2026

Bidirectional Extracellular Vesicle-Mediated Maternal-Embryonic Exchange in the Lecithotrophic Teleost Guppy

The placenta is defined as an organ that mediates the exchanges of nutrients, hormones, and other substances between the mother and embryo in viviparous animals. Its structure is diverse due to interspecific differences in fetal tissues and variation in the forms of maternal-fetal interfaces. Matrotrophic poeciliid teleosts, in which the embryo develops within the maternal ovarian follicle, possess functional placentas formed from maternal follicular and embryonic tissues. However, the physiological mechanisms underlying substrate exchange between mother and embryo remain unclear. Furthermore, although similar embryonic-maternal interfaces are observed in lecithotrophic poeciliids, it is unknown whether nutrient exchange occurs in these species. Therefore, this study investigated whether substance exchange occurs between the mother and embryo in the lecithotrophic teleost guppy (Poecilia reticulata) and identified the underlying physiological mechanisms. Histological analysis revealed that guppies have embryonic-maternal interfaces consisting of the maternal follicle and the embryonic yolk sac and pericardial sac. Additionally, tracking of 2,000 kDa fluorescein isothiocyanate-dextran injected into pregnant guppies confirmed its transport from mother to embryo. Immunofluorescence staining and electron microscopy revealed that substance transport from mother to embryo occurs via extracellular vesicles. Moreover, immunofluorescence staining and pharmacological experiments revealed exosome transport from embryo to mother. This study demonstrates that lecithotrophic guppies possess a functional placenta that mediates maternal-embryonic substrate transfer via extracellular vesicles. These findings provide fundamental insight into the evolution of placental strategies within the Poeciliidae family. Significance StatementViviparity, in which embryos develop within the maternal body, has evolved independently across diverse animal lineages. In lecithotrophic viviparity, embryos are thought to rely primarily on yolk-derived nutrients, with maternal-fetal exchange limited to small molecules such as gases. Here, using macromolecular tracer experiments and ultrastructural analyses in guppies, we show that large macromolecules (2000 kDa) are exchanged bidirectionally between mother and fetus via extracellular vesicles, despite the absence of direct tissue attachment. These findings challenge the conventional view of lecithotrophic viviparity and reveal a previously unrecognized mechanism of maternal-fetal communication. Our results suggest that extracellular vesicle-mediated exchange may represent a widespread and evolutionarily conserved strategy for maternal-fetal interaction across viviparous animals.

developmental biology↗

bioRxiv2026

The hAT transposon-like sequence homologous to Japanese medaka Tol2 was found in the European lamprey genome.

Tol2 is one of the few DNA-based transposable elements that reside in vertebrate genomes and retain transposition activity. It was first identified in the medaka fish (Oryzias latipes) and subsequently in another species of the genus Oryzias, which belongs to the order Beloniformes. Transposable elements similar in sequence to Tol2 also occur in several species of the order Cypriniformes, including the common carp. The low sequence variation of these elements relative to that of a nuclear gene provided evidence for past horizontal transfer events among host organisms. We collectively refer to Tol2 and these related elements as the Tol2 family. Here, we identified a novel transposable element in two European lamprey species (Lampetra fluviatilis and L. planeri), which we named Tel2. Lampreys belong to the jawless vertebrate lineage (infraphylum Agnatha), whereas all previously known host species of the Tol2 family are jawed vertebrates (infraphylum Gnathostomata). The nucleotide sequence similarity between Tol2 and Tel2 was higher than that observed for the nuclear gene, indicating at least one horizontal transfer event between the two infraphyla. Thus, the Tol2 family now includes Tel2 as a new member. These results indicate that Tol2 family elements have undergone multiple horizontal transfer events across a wide range of host organisms, including both jawless and jawed vertebrates. Because some members of this family still retain transposition activity, they provide an excellent and unique model for studying the role of horizontal transfer in the long-term persistence of DNA-based transposable elements.

genetics↗

bioRxiv2025

MHC Class I-like Gene in Squirrel Monkey Cytomegalovirus and the Evolution of the Virus

Homology searches between viral and human peptides revealed that the S9 protein of squirrel monkey cytomegalovirus (Saimiriine herpesvirus 4 strain [SBHV4]) shares 60.6% amino acid identity across 86.3% of full-length human HLA-A. This represents the most extensive and highest degree of homology reported to date between a viral protein and an MHC class I molecule. Phylogenetic analysis of MHC class I-like DNA sequences from primate HLA-A orthologs and SBHV4-S9 gene suggested that SBHV4-S9 was likely acquired via LINE-1-mediated horizontal gene transfer from the African Old World monkey Piliocolobus tephrosceles or a close ancestor 1.63-6.02 million years ago. SBHV4-S9 appeared to have undergone purifying selection following divergence from P. tephrosceles. Furthermore, phylogenetic analysis of the SBHV4-S1 gene and primate SLAMF6-like genes suggested that this gene was acquired after divergence from a close ancestor of the New World monkeys Saimiri oerstedii and Saimiri sciureus. Comprehensive evaluation of the similarity between eight SBHV4 genes (including S1 and S9) and their respective homologs in 241 primate species, assessed via PCA-syncmer-based Wasserstein distances, revealed that the overall relatedness between SBHV4 and African Cercopithecus ascanius, Cercopithecus pogonias, and Allenopithecus nigroviridis, respectively was significantly greater (i.e., exhibited shorter Wasserstein distances) in each case than that observed with all examined members of the genus Saimiri and Piliocolobus tephrosceles. Collectively, these findings indicate that SBHV4, although isolated from Saimiri sciureus in South America, appears to have a historical connection with Old World monkeys in Africa, despite the typically high host specificity of cytomegaloviruses.

microbiology↗

bioRxiv2025

The mechanism of Micafungin action to Pteropine orthoreovirus infection in human cell line

Pteropine orthoreovirus (PRV) is a fusogenic virus carried by bats that causes respiratory illnesses in humans. PRVs are transmitted from bats to humans and among humans. Micafungin (MCFG), an approved drug for fungal treatment, shows potential in inhibiting PRV propagation, although its precise mechanism of action remains unclear. This study aimed to investigate molecular mechanisms of MCFG during PRV propagation. Initially, molecular docking was employed to predict the primary target of MCFG. It was the p17 protein of PRV. Prior to examining the effect of MCFG on p17 suppression, differential gene expression analysis was performed to compare PRV-infected host cells with MCFG-treated cells, and it was found that IL-6 should be the main regulator induced by MCFG. Silencing IL-6 with siRNA markedly induced PRV release, syncytial formation, and marginally enhanced PRV RNA replication, corresponding to the main suppressive effects of MCFG against PRV. The p17, the presumed suppression target to inhibit syncytial formation by MCFG, markedly reduced syncytial formation but did not influence viral RNA replication. In contrast, MCFG significantly suppressed syncytial formation and slightly reduced PRV RNA replication, although both MCFG and anti-p17 antibody increased IL-6 mRNA expression. MCFG may inhibit other PRV proteins, like nonstructural replication protein (sigmaNS), which were found by molecular docking study. In conclusion, MCFG primarily targets p17 and modulates host immunity through IL-6, which likely interferes directly with syncytial formation.

microbiology↗

bioRxiv2024

Entomopoxvirus-like long DNA sequences in human centromeric and peri-centromeric regions

Mammalian genomes harbor a range of endogenous virus-like sequences, although these sequences are typically affected by mutations and deletions, and no examples have been reported of long, conserved regions extending tens of kilobases or more. In this study, a comprehensive similarity search against the complete human T2T genome (hT2T) using high-quality viral genome data was performed. Among nearly continuous viral sequences, the longest identified was Entomopoxvirus, spanning 140 kb with a similarity of over 57%. Notably, Entomopoxvirus-like sequences stood out within the human genome, with a total of 2.42 Mb exhibiting similarity to human sequences. Seven Entomopoxvirus species were fragmented into regions less than 40 kb each, with nearly all of these segments scattered throughout the human genome. Surprisingly, nearly all of these sequences were localized within the hsat1A regions of human centromeric and pericentromeric areas. On chromosome 3, for example, all sequences were confined within the centromere, and extensive transcription was observed across these regions. While the lack of fully sequenced genomes with solid annotations for other eukaryotic species limits our ability to infer the phylogenetic significance of these regions, our findings reveal remarkably long virus-like sequences within centromeric and related regions--as integral components of eukaryotic chromosomes.

bioinformatics↗

bioRxiv2024

RO8191, a new compound for initiating embryoimplantation in mice

During early pregnancy in mice, leukemia inhibitory factor (LIF) regulates embryo implantation by activating the JAK/STAT3 signaling pathway. The STAT3 pathway has been recognized to play a critical role in embryo implantation. However, it is not clear whether STAT3 activation itself can cause induction of embryo implantation. In this study, the effects of RO8191, a potential STAT3 activator, on embryo implantation were investigated through a series of studies with different mouse models. We found that the injection of RO8191 can induce embryo implantation by activating the STAT3 pathway in delayed implantation mice. Furthermore, RO8191 can initiate decidualization, which is essential for embryo implantation, in uterine epithelial-specific Stat3, Gp130, or Lifr conditional knockout (cKO) mice, which shows infertility due to embryo implantation failure. Histomorphological observations revealed that successful embryo implantation and embryonic development was seen in Lifr cKO mice. Increased epithelial detachment and vascularization were observed in Stat3 cKO mice, and excessive inflammatory response and embryo death were observed in Gp130 cKO mice. These results suggest that STAT3, Gp130 and LIFR each play a distinct role in embryo implantation and development. Although the specific mechanisms of RO8191 are not fully understood, the present study will provide insights to support the application of RO8191 in treating recuurent implantation failure.

developmental biology↗

bioRxiv2024

Regional differences in cell characteristics in electric eel electric organs indicate electrocyte development with ventral to dorsal migration.

Electric eels (Electrophorus) are renowned for their ability to generate electric discharge, which is used for prey capture and defense. Their electric organs (EOs) are located along the lateral-ventral region of the tail and contain electrocytes, which are multinucleated syncytium cells. The developmental origin of the electrocyte is mesodermal lineage cells observed in the ventral part of the myotome. However, it is unclear whether these precursor cells are also maintained in later stages and contribute to electric organ growth in adulthood. In this study, we report regional differences in cell morphology within the main EO (mEO) and identify a candidate cell population for electrocyte progenitors at the juvenile stages of Electrophorus. The cell morphology and distribution from the ventral terminal to the dorsal region of the mEO suggest the segregation of progenitors from the ventral cluster and their gradual transformation into mature multinucleated electrocytes via cell fusion and layering along the dorsal axis. Immunohistochemistry revealed strong expression of sodium-potassium adenosine triphosphatase (Na+/K+-ATPase), a key component in generating electric discharge in the mEO, across most mEO regions, except in the ventral cluster cells. Based on these observations, we propose that electrocyte progenitors develop from ventral cluster cells in the mEO and differentiate into mature multinucleated cells as they migrate dorsally. This is the first report to approach the developmental process of Electrophorus electrocytes from cell morphology and genetic profiles. Our findings represent a breakthrough in understanding the differentiation of electrocytes during the growth stages of Electrophorus.

developmental biology↗

bioRxiv2023

Membrane molecule bouncer enables follicle fertilization in a viviparous teleost: Poecilia reticulata (guppy)

Fertilization is a fundamental mechanism of sexual reproduction. Generally, oocytes are ovulated from the ovarian follicles and contact the sperm outside the ovarian medulla. Unlike this, follicle fertilization which means the egg contact with sperm in the ovarian medulla without ovulation is known in the viviparous teleost species belonging to the Poeciliidae. In this study, we focused on a viviparous teleost species, Poecilia reticulata (guppy). Our sperm tracking assay indicated that the sperm reached the immature oocytes with a germinal vesicle, and the fertilized immature oocytes were presumed to contribute to littermates. The binding between immature oocytes and sperm is a specific trait in the guppy, which was not observed in Danio rerio (zebrafish) or Oryzias latipes (medaka). The loss- and gain-of-function assays indicated that bouncer plays a critical role in immature oocyte-to-sperm binding. This fertilization trait in immature oocytes may provide certain advantages for females with respect to nutrition or other gestation costs. Our findings shed light on the unique reproductive strategies of guppy and contribute to our understanding of the diverse reproductive mechanisms in vertebrates. Summary statementUnlike general vertebrates, guppys oocyte fertilizes with sperm in the ovarian medulla at the immature stages. The distinctive trait depends on the Ly6/uPAR protein bouncer.

developmental biology↗

bioRxiv2022

FDA-approved drug screening identified micafungin as an antiviral agent against bat-borne emerging zoonotic Pteropine orthoreovirus

Bat-borne emerging zoonotic viruses cause major outbreaks, such as the Ebola virus, Nipah virus, severe acute respiratory syndrome (SARS) coronavirus, and SARS-CoV-2. Pteropine orthoreovirus (PRV), which spillover event occurred from fruit bats to humans, causes respiratory syndrome in humans widely in South East Asia. Repurposing approved drugs against PRV is a critical tool to confront future PRV pandemics. We screened 2,943 compounds in an FDA-approved drug library and identified eight hit compounds that reduce viral cytopathic effects on cultured Vero cells. Real-time quantitative PCR analysis revealed that six of eight hit compounds significantly inhibited PRV replication. Among them, micafungin used clinically as an antifungal drug, displayed a prominent antiviral effect on PRV. HighlightsO_LIA library of 2,943 FDA-approved drugs was screened to find potential antiviral drugs of Pteropine orthoreovirus. C_LIO_LISix hit compounds dramatically inhibited viral replication in vitro. C_LIO_LIMicafungin possessed antiviral activity to multiple strains of PRV. C_LI

pharmacology and toxicology↗

bioRxiv2022

Endocytosis-mediated vitellogenin absorption and lipid metabolism in the hindgut-derived pseudoplacenta of the viviparous teleost Xenotoca eiseni

Certain viviparous animals possess mechanisms for mother-to-embryo nutrient transport during gestation. Xenotoca eiseni is one such viviparous teleost species in which the mother supplies proteins and other components to the offspring developing in the ovary. The embryo possesses trophotenia, a hindgut-derived pseudoplacenta to receive the maternal supplement. However, the molecular mechanisms underlying viviparous non-mammalian animals remain elusive. We conducted this study to investigate the mechanism for nutrient absorption and degradation in trophoenia of X. eiseni. The tracer assay indicated that a lipid transfer protein, vitellogenin (Vtg), was absorbed into the epithelial layer cells of trophotaenia. Vtg uptake was significantly suppressed by Pitstop-2, an inhibitor of clathrin-mediated endocytosis. Gene expression analysis indicated that the genes involved in endocytosis-mediated lipolysis and lysosomal cholesterol transport were expressed in trophotaenia. In contrast, plasma membrane transporters expressed in the intestinal tract were not functional in trophotaenia. Our results suggested that endocytosis-mediated lysosomal lipolysis is one of the mechanisms underlying maternal component metabolism. Thus, our study demonstrated how viviparous teleost species have acquired a unique developmental system that is based on the hindgut-derived pseudoplacenta.

zoology↗

bioRxiv2021

Cubam receptor-mediated endocytosis in hindgut-derived pseudoplacenta of a viviparous teleost Xenotoca eiseni

Nutrient transfer from mother to the embryo is essential for reproduction in viviparous animals. In the viviparous teleost Xenotoca eiseni belonging to the family Goodeidae, the intraovarian embryo intakes the maternal component secreted into the ovarian fluid via the trophotaenia. Our previous study reported that the epithelial layer cells of the trophotaenia incorporate a maternal protein via vesicle trafficking. However, the molecules responsible for the absorption were still elusive. Here, we focused on Cubam (Cubilin-Amnionless) as a receptor involved in the absorption, and cathepsin L as a functional protease in the vesicles. Our results indicated that the Cubam receptor is distributed in the apical surface of the trophotaenia epithelium and then is taken into the intracellular vesicles. The trophotaenia possesses acidic organelles in epithelial layer cells and cathepsin L-dependent proteolysis activity. This evidence does not conflict with our hypothesis that receptor-mediated endocytosis and proteolysis play roles in maternal macromolecule absorption via the trohotaenia in viviparous teleosts. Such nutrient absorption involving endocytosis is not a specific trait in viviparous fish. Similar processes have been reported in the larval stage of oviparous fish or the suckling stage of viviparous mammals. Our findings suggest that the viviparous teleost acquired trophotaenia-based viviparity from a modification of the intestinal absorption system common in vertebrates. This is a fundamental study to understand the strategic variation of the reproductive system in vertebrates. Summary statementHere, we report that an endocytic pathway is a candidate for nutrient absorption in pseudoplacenta of a viviparous teleost. The trait may have developed from common intestinal mechanism among vertebrates.

zoology↗

bioRxiv2020

Heritable endogenization of an RNA virus in a mammalian species

Viruses are considered one of the driving forces for genome rearrangements via infection and endogenization into the host genome (Kazazian, 2004; Maksakova et al., 2006). In 2010, Horie and colleagues demonstrated that a non-retroviral RNA virus, Borna disease virus (BDV), could integrate into the genome in cultured somatic cells (Horie et al., 2010). However, germline transmission of viral-derived sequences using animal models is yet to be experimentally demonstrated. In this study, we reported a case of heritable endogenization using the encephalomyocarditis virus (EMCV) and laboratory mice. The EMCV is a small non-enveloped single-strand RNA virus without its own reverse transcriptase activity (Carocci et al., 2012). Here, we demonstrated that the EMCV genomic RNA was reverse transcribed into DNA fragments in the murine testes. The DNA sequence originated from the RNA genome of EMCV was also detected in the liver and earlobes of the offspring generated from the EMCV-infected father. This suggests that the exogenous sequence derived from the EMCV is transmitted into the host germline and inherited across subsequent generations. This first experimental demonstration of viral endogenization proposes reconsideration about the impact of viruses as a driving force for genome modification.

genetics↗