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Spermiogenesis defines the final phase of male germ cell differentiation. While multiple deubiquitinating enzymes have been linked to spermiogenesis, the impacts of deubiquitination on spermiogenesis remain poorly characterized. Here, we investigated the function of UAF1 in mouse spermiogenesis. We selectively deleted Uaf1 in premeiotic germ cells using the Stra8-Cre knock-in mouse strain (Uaf1 sKO), and found that Uaf1 is essential for spermiogenesis and male fertility. Further, UAF1 interacts and colocalizes with USP1 in the testes. Conditional knockout of Uaf1 in testes results in disturbed protein levels and localization of USP1, suggesting that UAF1 regulates spermiogenesis through the function of the deubiquitinating enzyme USP1. Using tandem mass tag-based proteomics, we identified that conditional knockout of Uaf1 in the testes results in reduced levels of proteins that are essential for spermiogenesis. Thus, we conclude that the UAF1/USP1 deubiquitinase complex is essential for normal spermiogenesis by regulating the levels of spermiogenesis-related proteins.
RESUMEN
BACKGROUND: Mitochondria produce adenosine triphosphate through respiratory activities to power sperm differentiation and motility, and decreased mitochondrial respiratory activity can result in poor sperm motility and asthenospermia. The mitochondrial sheath is a component of the mid-piece of the sperm flagellum, and dysfunction of the sheath can reduce sperm motility and cause male infertility. The membrane occupation and recognition nexus-motif protein 2 (MORN2) is testis enriched in mice, and the MORN motif was reported to play a role in the regulation of bioelectrical signal homeostasis in cardiomyocytes. METHODS: We generated Morn2-/- mice using CRISPR/Cas9 and evaluated the potential functions of MORN2 in spermiogenesis through histological analysis, fertility examination, RT-PCR, CASA, immunofluorescence, TUNEL, electron microscopy analysis, mitochondrial energy metabolism analysis, etc. RESULTS: The Morn2-/- mice were infertile, and their sperm showed severe motility defects. Morn2-/- sperm also had abnormal morphology characterized by bent heads, aberrant mitochondrial sheath formation, lower mitochondrial membrane potential, higher levels of reactive oxygen species, and decreased mitochondrial respiratory activity. CONCLUSIONS: Our study demonstrates that MORN2 is essential for male fertility and indicates that MORN2 functions in mitochondrial sheath formation and regulates mitochondrial respiratory activity.
Asunto(s)
Semen , Motilidad Espermática , Animales , Masculino , Ratones , Metabolismo Energético , Fertilidad , MitocondriasRESUMEN
Currently, obesity has achieved epidemic levels in reproductive-aged women with a myriad of consequences. Obesity is susceptible to several reproductive complications that eventually affect fertility rates. These complications originate from the deteriorated quality of oocytes from mothers with obesity, which increases the probability of chromosomal aneuploidy, elevated reactive oxygen species production, compromised embryonic developmental competency, and eventually reduced fertility. Maternal obesity is linked to pregnancy complications such as implantation error, abortion, miscarriage, and early pregnancy loss. This review highlights the adverse effects of maternal obesity on female fertility, with a focus on the mechanistic link between maternal obesity and oocyte quality and discusses possible measures to reduce its associated risks.
Asunto(s)
Obesidad Materna , Complicaciones del Embarazo , Embarazo , Femenino , Humanos , Fertilidad , Obesidad/complicaciones , Complicaciones del Embarazo/etiología , OocitosRESUMEN
A conceptually novel multi-bioinspired strategy based on structures and functions derived from the Namib desert beetle and lotus leaf is proposed in this paper. The proposed scheme synergistically combines the features of alternating wettability patterns and asymmetric wettability for improved directional water transport. Consequently, a Janus copper mesh, which substantially outperforms other single-bioinspired synthetic materials, is produced. The Janus copper mesh achieves directional self-transportation of tiny water droplets and continuous water flow in a gravity-irrelevant or an anti-gravity manner without energy consumption. This depends on the asymmetric wettability and alternating hydrophobic-hydrophilic wettability patterns on the hydrophobic surface of the mesh. In particular, Janus copper shows remarkable selective directional water transport in a water-oil system, rendering it a promising candidate for practical applications.
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We investigate dense relativistic electron mirror generation from a micro-droplet driven by circularly polarized Laguerre-Gaussian lasers. The surface electrons are expelled from the droplet by the laser's radial electric field and evolve into dense sheets after leaving the droplet. These electrons are trapped in the potential well of the laser's transverse ponderomotive force and are steadily accelerated to about 100 MeV by the longitudinal electric field. Particle-in-cell simulations indicate that the relativistic electron mirrors are characterized by high beam charge, narrow energy spread, and large angular momentum, which can be utilized for bright X/γ-ray emission and photon vortex formation.
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Matter can be transferred into energy and the opposite transformation is also possible by use of high-power lasers. A laser pulse in plasma can convert its energy into γ-rays and then e - e + pairs via the multi-photon Breit-Wheeler process. Production of dense positrons at GeV energies is very challenging since extremely high laser intensity ~1024 Wcm-2 is required. Here we propose an all-optical scheme for ultra-bright γ-ray emission and dense positron production with lasers at intensity of 1022-23 Wcm-2. By irradiating two colliding elliptically-polarized lasers onto two diamondlike carbon foils, electrons in the focal region of one foil are rapidly accelerated by the laser radiation pressure and interact with the other intense laser pulse which penetrates through the second foil due to relativistically induced foil transparency. This symmetric configuration enables efficient Compton back-scattering and results in ultra-bright γ-photon emission with brightness of ~1025 photons/s/mm2/mrad2/0.1%BW at 15 MeV and intensity of 5 × 1023 Wcm-2. Our first three-dimensional simulation with quantum-electrodynamics incorporated shows that a GeV positron beam with density of 2.5 × 1022 cm-3 and flux of 1.6 × 1010/shot is achieved. Collective effects of the pair plasma may be also triggered, offering a window on investigating laboratory astrophysics at PW laser facilities.
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We propose a novel scheme to generate ultra-bright ultra-short γ-ray flashes and high-energy-density attosecond positron bunches by using multi-dimensional particle-in-cell simulations with quantum electrodynamics effects incorporated. By irradiating a 10 PW laser pulse with an intensity of 1023 W/cm2 onto a micro-wire target, surface electrons are dragged-out of the micro-wire and are effectively accelerated to several GeV energies by the laser ponderomotive force, forming relativistic attosecond electron bunches. When these electrons interact with the probe pulse from the other side, ultra-short γ-ray flashes are emitted with an ultra-high peak brightness of 1.8 × 1024 photons s-1mm-2mrad-2 per 0.1%BW at 24 MeV. These photons propagate with a low divergence and collide with the probe pulse, triggering the Breit-Wheeler process. Dense attosecond e-e+ pair bunches are produced with the positron energy density as high as 1017 J/m3 and number of 109. Such ultra-bright ultra-short γ-ray flashes and secondary positron beams may have potential applications in fundamental physics, high-energy-density physics, applied science and laboratory astrophysics.