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Mitochondrial replacement therapy (MRT) has been used to prevent maternal transmission of disease-causing mutations in mitochondrial DNA (mtDNA). However, because MRT requires nuclear transfer, it carries the risk of mtDNA carryover and hence of the reversion of mtDNA to pathogenic levels owing to selective replication and genetic drift. Here we show in HeLa cells, mouse embryos and human embryos that mtDNA heteroplasmy can be reduced by pre-labelling the mitochondrial outer membrane of a donor zygote via microinjection with an mRNA coding for a transmembrane peptide fused to an autophagy receptor, to induce the degradation of the labelled mitochondria via forced mitophagy. Forced mitophagy reduced mtDNA carryover in newly reconstructed embryos after MRT, and had negligible effects on the growth curve, reproduction, exercise capacity and other behavioural characteristics of the offspring mice. The induction of forced mitophagy to degrade undesired donor mtDNA may increase the clinical feasibility of MRT and could be extended to other nuclear transfer techniques.

Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis, are widespread in developed countries and gradually increasing in developing countries. Evidences showed that man with CD has a decrease of serum testosterone, but how IBD take effects on testicular testosterone synthesis is not well elucidated. To investigate the effects of IBD on testis, we analyzed testicular metabolome and transcriptome data of the dextran sulfate sodium (DSS) induced IBD mice. As a result, metabolomic data showed that DSS indeed induced androgen decrease in mouse testis. Correspondingly, androgen synthesis associated genes, especially Lhcgr, were down-regulated in DSS testis. From the metabolomic data, we found vitamin intake associated metabolites vitamin B2 and pyridoxamine were significantly decreased, whereas fatty acid metabolism associated molecules N-lauroylglycine and N-decanoylglycine were increased in DSS testis. In addition, we found 8-hydroxy-deoxyguanosine, a DNA oxidative damage marker, and 8-oxoguanine, a molecule responsible for DNA damage repair, were also changed in DSS testis. Simultaneously, our data also showed that DSS up-regulated the expression of meiosis initiation associated gene Stra8 and oxygen transport associated genes in testis. In summary, these results depicted the complex effects of colitis on testis. These metabolites and transcripts changed in DSS testis could be used as potential targets for IBD treatment or symptom relieve.

With the rapid change of people's lifestyle, more childbearing couples live with irregular schedules (i.e., staying up late) and suffer from decreased fertility and abortion, which can be caused by luteal phase defect (LPD). We used continuous light-exposed mice as a model to observe whether continuous light exposure may affect luteinization and luteal function. We showed that the level of progesterone in serum reduced (p .001), the number of corpus luteum (CL) decreased (p .01), and the expressions of luteinization-related genes (Lhcgr, Star, Ptgfr, and Runx2), clock genes (Clock and Per1), and Mt1 were downregulated (p .05) in the ovaries of mice exposed to continuous light, suggesting that continuous light exposure induces defects in luteinization and luteal functions. Strikingly, injection of melatonin (3 mg/kg) could improve luteal functions in continuous light-exposed mice. Moreover, we found that, after 2 h of hCG injection, the level of pERK1/2 in the ovary decreased in the continuous light group, but increased in the melatonin administration group, suggesting that melatonin can improve LPD caused by continuous light exposure through activating the ERK1/2 pathway. In summary, our data demonstrate that continuous light exposure affects ovary luteinization and luteal function, which can be rescued by melatonin.

Uncontrolled pathogenic genome mutations in germline cells might impair adult fertility, lead to birth defects or even affect the adaptability of a species. Understanding the sources of DNA damage, as well as the features of damage response in germline cells are the overarching tasks to reduce the mutations in germline cells. With the accumulation of human genome data and genetic reports, genome variants formed in germline cells are being extensively explored. However, the sources of DNA damage, the damage repair mechanisms, and the effects of DNA damage or mutations on the development of germline cells are still unclear. Besides exogenous triggers of DNA damage such as irradiation and genotoxic chemicals, endogenous exposure to inflammation may also contribute to the genome instability of germline cells. In this review, we summarized the features of de novo mutations and the specific DNA damage responses in germline cells and explored the possible roles of inflammation on the genome stability of germline cells.

Within the development of ovarian follicle, in addition to cell proliferation and differentiation, sophisticated cell–cell cross talks are established among follicular somatic cells such as granulosa cells (GCs) and theca cells. To systematically reveal the cell differentiation and signal transductions in follicular somatic cells, we collected the mouse follicular somatic cells from secondary to ovulatory stage, and analyzed the single cell transcriptomes. Having data filtered and screened, we found 6883 high variable genes in 4888 single cells. Then follicular somatic cells were clustered into 26 cell clusters, including 18 GC clusters, 4 theca endocrine cell (TEC) clusters, and 4 other somatic cell clusters, which include immune cells and Acta2 positive theca externa cells. From our data, we found there was metabolic reprogramming happened during GC differentiation. We also found both Cyp19a1 and Cyp11a1 could be expressed in TECs. We analyzed the expression patterns of genes associated with cell–cell interactions such as steroid hormone receptor genes, insulin signaling genes, and cytokine/transformation growth factor beta associated genes in all cell clusters. Lastly, we clustered the highly variable genes into 300 gene clusters, which could be used to search new genes involved in follicle development. These transcriptomes of follicular somatic cells provide us potential clues to reveal how mammals regulating follicle development and could help us find targets to improve oocyte quality for women with low fertility. Summary sentence In total, 6883 high variable genes are found in 4888 ovarian follicular somatic cells.

Insufficiency of oocyte activation impairs the subsequent embryo development in assisted reproductive technology (ART). Intracellular Ca2+ concentration ([Ca2+]i) oscillations switch the oocytes to resume the second meiosis and initiate embryonic development. However, the [Ca2+]i oscillation patterns in oocytes are poorly characterized. In this study, we investigated the effects of various factors, such as the oocytes age, pH, cumulus cells, in vitro or in vivo maturation, and ER stress on [Ca2+]i oscillation patterns and pronuclear formation after parthenogenetic activation of mouse oocytes. Our results showed that the oocytes released to the oviduct at 17 h post-human chorionic gonadotrophin (hCG) displayed a significantly stronger [Ca2+]i oscillation, including higher frequency, shorter cycle, and higher peak, compared with oocytes collected at earlier or later time points. [Ca2+]i oscillations in acidic conditions (pH 6.4 and 6.6) were significantly weaker than those in neutral and mildly alkaline conditions (pH from 6.8 to 7.6). In vitro-matured oocytes showed reduced frequency and peak of [Ca2+]i oscillations compared with those matured in vivo. In vitro-matured oocytes from the cumulus-oocyte complexes (COCs) showed a significantly higher frequency, shorter cycle, and higher peak compared with the denuded oocytes (DOs). Finally, endoplasmic reticulum stress (ER stress) severely affected the parameters of [Ca2+]i oscillations, including elongated cycles and lower frequency. The pronuclear (PN) rate of oocytes after parthenogenetic activation was correlated with [Ca2+]i oscillation pattern, decreasing with oocyte aging, cumulus removal, acidic pH, and increasing ER stress. These results provide fundamental but critical information for the mechanism of how these factors affect oocyte activation.

In animals, feeding can regulate release of digestive enzymes. Digestive enzymes are produced and released in response to specific ratios of nutrients, so the quality and quantity of food ingested are important factors in the secretion and activity of digestive enzymes. In general, the enzyme activity and secretion in the fed insects are relatively higher than that in the unfed insects. Neuropeptides and peptide hormones are important regulators of enzyme activity. In several insects, the neuropeptide sulfakinin (SK) is known to be a regulator of feeding and digestion similar to cholecystokinin in mammals. However, the roles of diet and SK in regulation of activity of digestive enzymes in the important pest insect, the brown planthopper (Nilaparvata lugens), are unknown. In this study, we identified six genes encoding different digestive enzymes and cloned three of these. We found that enzymatic activity and transcriptional levels of digestive enzymatic activity genes were upregulated by refeeding animals for 5 h after 24 h starvation. Furthermore, injection of N. lugens SK reduces digestive enzyme activity and leads to a downregulation of digestive enzyme gene transcripts. This study provides new views into the action of diet and SK in regulation of digestive enzymes in (hemimetabolous) insects. Taken together with the roles of SK in inducing satiety, our data strongly suggest that SK signaling is important in regulation of food ingestion and processing.

Exotic domain-wall phenomena make ferroelectrics the candidates for nanoelectronics. The local symmetry and structure anomalies at domain walls have raised interest in the unusual functionalities, such as domain wall chirality and conductivity. Especially, the spontaneous lattice distortion and symmetry breaking at domain walls activate them as the location of structural transformation. However, the routes to achieve ferroelectric-antiferroelectric phase transition via ferroelectric domain walls remain challenging, which are important to develop materials for energy storage and conversion. Here, we have observed stepwise antiferroelectric phase transition in strained pure BiFeO3 ultrathin films derived from ferroelectric domain walls. Aberration-corrected transmission electron microscopy observation reveals that the resultant phase transition is mediated by dense 180° domain walls via providing the antiparallel cation displacement, cooperating with the enhanced interfacial oxygen octahedral clamping. First-principles calculations further confirm the critical role of interfacial oxygen octahedral coupling during this transition. These findings report an alternative route for antiferroelectric phase transition. Besides, our results provide fresh insights into functionalities of ferroelectric domain walls and open a venue for developing energy-storage materials based on domain engineering.

Retention failure is deleterious on ferroelectric domain stability, resulting in data loss in ferroelectric memories. However, the understanding of the origin of retention failure remains a challenge for the lack of a direct experimental evidence. Here, using a combination of piezoelectric force microscopy, atomic-scale scanning transmission electron microscopy and reciprocal space mapping, we report that the polarization retention failure is caused by a strain gradient induced flexoelectric field in tetragonal ferroelectric films. Atomic imaging reveals that the strain gradient is introduced by tensile strains, which is resultant from the vertically distributed Pb-rich anti-phase domains. This strain gradient couples with polarizations and results in flexoelectric fields in the films, leading to the retention failure in the films. Our study directly underlines the atomic mechanisms behind the strain gradient induced macroscopic retention failure behavior and clarifies the effect of local strain state on domain relaxation processes, thus can shed light on further understanding and improving the retention properties of oxide ferroelectrics.

Phase coexistence in ferroelectric oxide films displays complex phase competitions and transformation which suggest new multiple-coupled properties. Here we have successfully engineered the coexistence of flux-closure and a1/a2 phases in tensile-strained PbTiO3 films sandwiched between GdScO3 substrate and a SrTiO3 layer. Moreover, by using in-situ electron beam illumination, the unusual transformation from a1/a2 phase to the flux-closure phase was directly observed. In detail, there are two types of transformations: One is the nucleation, growth, and expansion of the flux-closure phase from the internal region of the a1/a2 phase. The other feature is a “dislocation gliding” like behavior: a thin lamella of a1/a2 shrinks like “partial dislocation pairs” and finally the gradually disappeared a1/a2 lamella forms a “perfect dislocation” in the flux-closure domain matrix. Phase-field simulations suggest that the a1/a2 to flux-closure transition is induced by the decrease of the depolarization field, which is screened by the injected electrons from electron beam irradiation. These results directly confirm the phase interconversion under an external stimulus at the nanometer scale, which shed new light on the fabrication of new polar textures.

Ferroelectrics exhibit polarization tunable resistance switching behaviors, which are promising for next-generation non-volatile memory devices. For technological applications, thinner nanoscale arrays are expected, which feature with higher density and larger ON/OFF (RON/OFF) ratios in the metal/ferroelectrics/semiconductor heterojunction. Here, we acquire high density BiFeO3 (BFO) nano-islands around 10 nm in thickness displaying a high RON/OFF ratio of 103, comparable to the tunnel junctions. Moreover, both the macroscopic and microscopic resistive switching behaviors of the present BiFeO3 films reveal an unexpected the filamentary-type resistive switching which is modified by the charged domain walls in nano-islands dominated by the center-type domains. Particularly, the charged domain walls spontaneously formed within the BFO nano-islands are proposed as the conductive paths based on the redistribution of carriers under the applied voltages. Potential applications for memories with large RON/OFF ratios of such kind of configurable charged domain walls are demonstrated.

Cell division consists of nuclear division (mitosis for somatic cells and meiosis for germ cells) and cytoplasmic division (cytokinesis). Embryonic developments are highly programmed, and thus, each cellular event during early embryo development is stable. For mouse embryos, the first time of mitosis is completed about 22 h after fertilization. However, it remains unclear when the embryo completes its first cytokinesis. Here, we microinjected only one cell in the 2-cell stage mouse embryos with mRNA, which encodes green fluorescence protein (GFP). By monitoring the GFP protein transport dynamics between the two cells, we demonstrated that the first time of cytokinesis in mouse embryos is completed about 15 h after mitosis, namely 37 h after fertilization. In addition, our results indicate that the cytoplasmic protein transport between daughter cells is very effective, which relies on microtubules instead of microfilaments in 2-cell mouse embryos. These results should enrich people’s understanding of the first cell division and cytoskeleton in mouse embryos and then learn more about the mechanisms of early embryo development in mammals.

Feeding is essential for animal survival and reproduction and is regulated by both internal states and external stimuli. However, little is known about how internal states influence the perception of external sensory cues that regulate feeding behavior. Here, we investigated the neuronal and molecular mechanisms behind nutritional state-mediated regulation of gustatory perception in control of feeding behavior in the brown planthopper and Drosophila. We found that feeding increases the expression of the cholecystokinin-like peptide, sulfakinin (SK), and the activity of a set of SK-expressing neurons. Starvation elevates the transcription of the sugar receptor Gr64f and SK negatively regulates the expression of Gr64f in both insects. Interestingly, we found that one of the two known SK receptors, CCKLR-17D3, is expressed by some of Gr64f-expressing neurons in the proboscis and proleg tarsi. Thus, we have identified SK as a neuropeptide signal in a neuronal circuitry that responds to food intake, and regulates feeding behavior by diminishing gustatory receptor gene expression and activity of sweet sensing GRNs. Our findings demonstrate one nutritional state-dependent pathway that modulates sweet perception and thereby feeding behavior, but our experiments cannot exclude further parallel pathways. Importantly, we show that the underlying mechanisms are conserved in the two distantly related insect species., Author summary Food intake is critical for animal survival and reproduction and is regulated both by internal states that signal appetite or satiety, and by external sensory stimuli. It is well known that the internal nutritional state influences the strength of the chemosensory perception of food signals. Thus, both gustatory and olfactory signals of preferred food are strengthened in hungry animals. However, the molecular mechanisms behind satiety-mediated modulation of taste are still not known. We show here that cholecystokinin-like (SK) peptide in brown planthopper and Drosophila signals satiety and inhibits sugar attraction by lowering the activity of sweet-sensing gustatory neurons and transcription of a sugar receptor gene, Gr64f. We show that SK peptide signaling reflects the nutritional state and inhibits feeding behavior. Re-feeding after starvation increases SK peptide expression and spontaneous activity of SK producing neurons. Interestingly, we found that SK peptide negatively regulates the expression of the sweet gustatory receptor and that activation of SK producing neurons inhibits the activity of sweet-sensing gustatory neurons (GRNs). Furthermore, we found that one of the two known SK peptide receptors is expressed in some sweet-sensing GRNs in the proboscis and proleg tarsi. In summary, our findings provide a mechanism that is conserved in distantly related insects and which explains how feeding state modulates sweet perception to regulate feeding behavior. Thus, we have identified a neuropeptide signal and its neuronal circuitry that respond to satiety, and that regulate feeding behavior by inhibiting gustatory receptor gene expression and activity of sweet sensing GRNs.

Germ cell-derived genomic structure variants not only drive the evolution of species but also induce developmental defects in offspring. The genomic structure variants have different types, but most of them are originated from DNA double-strand breaks (DSBs). It is still not well known whether DNA DSBs exist in adult mammalian oocytes and how the growing and fully grown oocytes repair their DNA DSBs induced by endogenous or exogenous factors. In this study, we detected the endogenous DNA DSBs in the growing and fully grown mouse oocytes and found that the DNA DSBs mainly localized at the centromere-adjacent regions, which are also copy number variation hotspots. When the exogenous DNA DSBs were introduced by Etoposide, we found that Rad51-mediated homologous recombination (HR) was used to repair the broken DNA. However, the HR repair caused the chromatin intertwined and impaired the homologous chromosome segregation in oocytes. Although we had not detected the indication about HR repair of endogenous centromere-adjacent DNA DSBs, we found that Rad52 and RNA:DNA hybrids colocalized with these DNA DSBs, indicating that a Rad52-dependent DNA repair might exist in oocytes. In summary, our results not only demonstrated an association between endogenous DNA DSBs with genomic structure variants but also revealed one specific DNA DSB repair manner in oocytes.

Domain behavior of (111)- oriented perovskite ferroelectric films is significantly different from (001)-/(101)- oriented ones, resulting in enhancing property responses such as a superior susceptibility and a reduced coercive field. However, the domain structures and evolutions with the thickness of (111)-oriented ferroelectric films, which are crucial to further understand the distinctive properties, are still obscure. In this study, the ferroelectric domains of (111)- oriented PbTiO3 films are investigated by transmission electronic microscopy (TEM) and piezoresponse force microscopy (PFM). We identify the domain evolution with the film thicknesses under anisotropic strains imposed by the orthorhombic GdScO3 (101)O substrates. Contrast analysis and electron diffraction patterns reveal that only four ferroelectric variants evolve in PTO films: d2+, d2-, d3+ and d3-, with the polarization directions along [010], [0 1 ¯ 0], [001] and [00 1 ¯ ], respectively. Two kinds of domain walls are formed: “inclined” (011) domain walls for d2-/d3+ (d2+/d3-) domains, “normal” (01 1 ¯ ) domain walls for d2-/d3+ (d2+/d3-) domains. The width of periodically distributed d2+/d3+ (d2-/d3-) domains increases with film thickness following the square root rule. Aberration-corrected scanning transmission electronic microscopy demonstrates the lattice characteristics of domains in (111)- oriented PbTiO3 films are consistent with tetragonal ferroelectric domains. PFM studies reveal that both the out-of-plane and in-plane polarization components of d2-/d3+ (d2+/d3-) domains are non-identical, whereas the d2+/d3+ (d2-/d3-) domains possess uniform out-of-plane polarization component and non-uniform in-plane polarization component. This study discloses the domain structure in (111)- oriented tetragonal ferroelectric films under anisotropic strains and the association with the ferroelectric properties.

Break-induced replication (BIR) is essential for the repair of DNA double-strand breaks (DSBs) with single ends. DSBs-induced microhomology-mediated BIR (mmBIR) and template-switching can increase the risk of complex genome rearrangement. In addition, DSBs can also induce the multi-invasion-mediated DSB amplification. The mmBIR-induced genomic rearrangement has been identified in cancer cells and patients with rare diseases. However, when and how mmBIR is initiated have not been fully and deeply studied. Furthermore, it is not well understood about the conditions for initiation of multi-invasion-mediated DSB amplification. In the G2 phase oocyte of mouse, we identified a type of short-scale BIR (ssBIR) using the DNA replication indicator 5-ethynyl-2’-deoxyuridine (EdU). These ssBIRs could only be induced in the fully grown oocytes but not the growing oocytes. If the DSB oocytes were treated with Rad51 or Chek1/2 inhibitors, both EdU signals and DSB marker γH2A.X foci would decrease. In addition, the DNA polymerase inhibitor Aphidicolin could inhibit the ssBIR and another inhibitor ddATP could reduce the number of γH2A.X foci in the DSB oocytes. In conclusion, our results showed that DNA DSBs in the fully grown oocytes can initiate ssBIR and be amplified by Rad51 or DNA replication.

SUMMARYFeeding is essential for animal survival and reproduction and is regulated by both internal states and external stimuli. However, little is known about how internal states influence the perception of external sensory cues that regulate feeding behavior. Here, we investigated the neuronal and molecular mechanisms behind nutritional state-mediated regulation of gustatory perception in control of feeding behavior in the brown planthopper and Drosophila. We found that feeding increases the expression of the cholecystokinin-like peptide, sulfakinin (SK), and the activity of a set of SK-expressing neurons. Starvation elevates the transcription of the sugar receptor Gr64f and SK negatively regulates the expression of Gr64f in both insects. This Gr64f regulation is by direct action of SK neurons on Gr64f-expressing neurons of the proboscis and proleg tarsi that co-express the SK receptor CCKLR-17D3. Our findings thus demonstrate how nutritional state induces peptide signaling to modulate sweet perception and thereby feeding behavior.

Insufficiency of oocyte activation impairs the subsequent embryo development in assisted reproductive technology (ART). Intracellular Ca(2+) concentration ([Ca(2+)]i) oscillations switch the oocytes to resume the second meiosis and initiate embryonic development. However, the [Ca(2+)]i oscillation patterns in oocytes are poorly characterized. In this study, we investigated the effects of various factors, such as the oocytes age, pH, cumulus cells, in vitro or in vivo maturation, and ER stress on [Ca(2+)]i oscillation patterns and pronuclear formation after parthenogenetic activation of mouse oocytes. Our results showed that the oocytes released to the oviduct at 17 h post-human chorionic gonadotrophin (hCG) displayed a significantly stronger [Ca(2+)]i oscillation, including higher frequency, shorter cycle, and higher peak, compared with oocytes collected at earlier or later time points. [Ca(2+)]i oscillations in acidic conditions (pH 6.4 and 6.6) were significantly weaker than those in neutral and mildly alkaline conditions (pH from 6.8 to 7.6). In vitro-matured oocytes showed reduced frequency and peak of [Ca(2+)]i oscillations compared with those matured in vivo. In vitro-matured oocytes from the cumulus-oocyte complexes (COCs) showed a significantly higher frequency, shorter cycle, and higher peak compared with the denuded oocytes (DOs). Finally, endoplasmic reticulum stress (ER stress) severely affected the parameters of [Ca(2+)]i oscillations, including elongated cycles and lower frequency. The pronuclear (PN) rate of oocytes after parthenogenetic activation was correlated with [Ca(2+)]i oscillation pattern, decreasing with oocyte aging, cumulus removal, acidic pH, and increasing ER stress. These results provide fundamental but critical information for the mechanism of how these factors affect oocyte activation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-021-02100-9.

Cruciform DNA is a causing factor of genome instability and chromosomal translocation, however, most studies about cruciform DNA in mammalian cells were based on palindromic sequences containing plasmids and reports about endogenous cruciform DNA are rare. In this study we observed the dynamics of endogenous cruciform DNA in mouse growing oocytes using immunofluorescence labeling method. We found cruciform DNA foci exist in transcription active growing oocytes but not in transcription inactive fully grown oocytes and colocalized with Parp1 but not with DNA damage marker γH2A.X. By analyzing the Genotype-Tissue Expression data, we found cruciform DNA-mediated chromosomal translocation in human spermatocytes is associated with the specific DNA transcription in testis. When inhibiting the transcription with α-amanitin in mouse oocytes, we found oocyte cruciform DNA foci decreased significantly. In summary, we observed the endogenous cruciform DNA in growing oocytes and our results showed that the cruciform DNA formation is transcription-dependent.

Break-induced DNA replication (BIR) have been detected not only in the genome of rare disease patients but also in cancer cells, however, the mechanisms of BIR formation haven’t been explained in details. In the late G2 phase-like mouse oocytes, we found DNA double-strand breaks (DSBs) could induce Rad51 dependent small-scale DNA replication. In addition, we also found the DSBs could be amplified in mouse oocytes, and the amplification could be inhibited by Rad51 inhibitor IBR2 and DNA replication inhibitor ddATP. Lastly, we found the DSB repair was relatively inefficiency in hybrid mouse oocytes compared with that of the purebred mouse oocytes. We found DSBs could induce BIR more easier in hybrid mouse oocytes, indicating the DNA repair in oocytes could be affected by the sequence differences between homologous chromatids. In summary, our results indicated that the condensed chromatin configuration in late G2 phase and the sequence similarity between broken DNA and template DNA are causing factors of BIR in mammalian genome, and the DNA damage could be amplified in late G2 phase cells.

Female germ cell development consists of complex events including sex determination, meiosis initiation, retardation and resumption. During early oogenesis, the asynchrony of the transition from mitosis to meiosis results in heterogeneity in the female germ cell populations at a certain embryonic stage, which limits the studies of meiosis initiation and progression at a higher resolution level. Here, we investigated the transcriptional profiles of 19363 single germ cells collected from E12.5, E14.5 and E16.5 mouse fetal ovaries. Clustering analysis identified seven groups and defined dozens of corresponding transcription factors, providing a global view of cellular differentiation from primordial germ cells towards meiocytes. Further, we explored the dynamics of gene expression within the developmental trajectory with special focus on the mechanisms underlying meiotic initiation. We found thatDpy30may be involved in the regulation of meiosis initiation at the epigenetic level. Our data provide key insights into the transcriptome features of peri-meiotic female germ cells, which offers new information not only on meiosis initiation and progression but also on screening pathogenic mutations in meiosis-associated diseases.

Meiosis initiation is a crucial step for the production of haploid gametes, which occurs from anterior to posterior in fetal ovaries. The asynchrony of the transition from mitosis to meiosis results in heterogeneity in the female germ cell populations, which limits the studies of meiosis initiation and progression at a higher resolution level. To dissect the process of meiosis initiation, we investigated the transcriptional profiles of 19 363 single germ cells collected from E12.5, E14.5, and E16.5 mouse fetal ovaries. Clustering analysis identified seven groups and defined dozens of corresponding transcription factors, providing a global view of cellular differentiation from primordial germ cells toward meiocytes. Furthermore, we explored the dynamics of gene expression within the developmental trajectory with special focus on the critical state of meiosis. We found that meiosis initiation occurs as early as E12.5 and the cluster of oogonia_4 is the critical state between mitosis and meiosis. Our data provide key insights into the transcriptome features of peri-meiotic female germ cells, which offers new information not only on meiosis initiation and progression but also on screening pathogenic mutations in meiosis-associated diseases.

One of the main causes of pregnancy failure and fetus abortion is oocyte aneuploidy, which is increased with maternal aging. Numerous possible causes of oocyte aneuploidy in aged women have been proposed, including cross-over formation defect, cohesin loss, spindle deformation, spindle assembly checkpoint malfunction, microtubule-kinetochore attachment failure, kinetochore mis-orientation, mitochondria dysfunction-induced increases in reactive oxygen species, protein over-acetylation, and DNA damage. However, it still needs to be answered if these aneuploidization factors have inherent relations, and how to prevent chromosome aneuploidy in aged oocytes. Epidemiologically, oocyte aneuploidy has been found to be weakly associated with higher homocysteine concentrations, obesity, ionizing radiation and even seasonality. In this review, we summarize the research progress and present an integrated view of oocyte aneuploidization.

Tributyltin oxide (TBTO) has been widely used as marine antifouling composition, preservative, biocide, and a stabilizer in plastic industry. Previous studies have indicated that TBTO can cause immunotoxicity as an environmental pollutant. However, little is known about its reproductive toxicity, especially on female oocyte maturation and the underlying mechanisms. In this study, mouse oocytes were cultured with different concentrations of TBTO in vitro, and several crucial events during meiotic maturation were evaluated. We found that the first polar body extrusion rate was significantly reduced, which reflected the disruption of meiotic maturation. The rate of abnormal spindle organization increased significantly, accompanied with a higher rate of chromosome misalignment. In addition, TBTO treatment increased reactive oxygen species generation markedly, which also accelerated the early-stage apoptosis. Moreover, heterogeneous mitochondrial distribution, mitochondrial dysfunction, and higher rate of aneuploidy were detected, which consequently disrupted in vitro fertilization. In conclusion, our results indicated that TBTO exposure could impair mouse oocyte maturation by affecting spindle organization, chromosome alignment, mitochondria functions, oxidative stress, and apoptosis.

Previous studies suggest that hydrogen sulfide (H2S) and ammonia (NH3) are two major air pollutants which can cause damage to porcine health. However, the mechanisms underlying toxic effects of these compounds on porcine oocyte maturation are not clear. To clarify the mechanism, we evaluated the oocyte quality by detecting some events during oocytes maturation. In our study, porcine oocytes were cultured with different concentrations of Na2S and/or NH4Cl in vitro and the rate of the first polar body extrusion decreased significantly. Also, actin filament was seriously disrupted to damage the cytoskeleton which resulted in reduced rate of oocyte maturation. We explored the reactive oxygen species (ROS) generation and found that the ROS level was increased significantly after Na2S treatment but not after NH4Cl treatment. Moreover, early stage apoptosis rate was significantly increased and autophagy protein LC3 B expression level was higher in oocytes treated with Na2S and/or NH4Cl, which might be caused by ROS elevation. Additionally, exposure to Na2S and/or NH4Cl also caused ROS generation and early apoptosis in cumulus cells, which might further affect oocyte maturation in vitro. In summary, our data suggested that exposure to H2S and/or NH3 decreased porcine oocyte maturation in vitro, which might be caused by actin disruption, ROS generation, early apoptosis and autophagy.

Coexistence of two phases creates a morphotropic phase boundary in perovskite oxides, which can provide large piezoelectric response, generating it a well suited system for probe-based memories and actuator applications. The coexistence of two phases in thin films is proposed to be induced by epitaxial constraints from substrates or chemical compositional modifications by substitution. In this work, we found a new formation mechanism of two-phase coexistence driven by interfacial oxygen octahedral coupling (OOC) in oxide heterostructures. We fabricated a series of BiFeO 3 (BFO) ultrathin films on various orthorhombic substrates exerting from tensile to compressive strains by Pulsed Laser Deposition (PLD) techniques. Aberration-corrected transmission electron microscopy demonstrates that the lattice rotation and oxygen octahedral rotation (OOR) patterns transfer from these substrates to BFO films in about 3 unit cells while an orthorhombic ( Pnma ) phase forms at the interface due to OOC. This Pnma phase is non-polar, which differs from polar phases of Ima2 or Pmc2 1 when a large tensile strain is imposed onto BFO. First-principles calculations reproduce these experimental results perfectly. This phase transition occurs when BFO films are under both tensile and compressive strains suggesting that OOC alone can induce phase transition in ultrathin BFO films. Such coexistence of two phases may have many potential applications in the field of electronics, such as ferroelectric sensors and actuators.