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1.
Nature ; 627(8004): 505-509, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38418881

ABSTRACT

The Double Asteroid Redirection Test (DART) had an impact with Dimorphos (a satellite of the asteroid Didymos) on 26 September 20221. Ground-based observations showed that the Didymos system brightened by a factor of 8.3 after the impact because of ejecta, returning to the pre-impact brightness 23.7 days afterwards2. Hubble Space Telescope observations made from 15 minutes after impact to 18.5 days after, with a spatial resolution of 2.1 kilometres per pixel, showed a complex evolution of the ejecta3, consistent with other asteroid impact events. The momentum enhancement factor, determined using the measured binary period change4, ranges between 2.2 and 4.9, depending on the assumptions about the mass and density of Dimorphos5. Here we report observations from the LUKE and LEIA instruments on the LICIACube cube satellite, which was deployed 15 days in advance of the impact of DART. Data were taken from 71 seconds before the impact until 320 seconds afterwards. The ejecta plume was a cone with an aperture angle of 140 ± 4 degrees. The inner region of the plume was blue, becoming redder with increasing distance from Dimorphos. The ejecta plume exhibited a complex and inhomogeneous structure, characterized by filaments, dust grains and single or clustered boulders. The ejecta velocities ranged from a few tens of metres per second to about 500 metres per second.

2.
Nat Commun ; 11(1): 2655, 2020 05 27.
Article in English | MEDLINE | ID: mdl-32461569

ABSTRACT

Asteroid shapes and hydration levels can serve as tracers of their history and origin. For instance, the asteroids (162173) Ryugu and (101955) Bennu have an oblate spheroidal shape with a pronounced equator, but contain different surface hydration levels. Here we show, through numerical simulations of large asteroid disruptions, that oblate spheroids, some of which have a pronounced equator defining a spinning top shape, can form directly through gravitational reaccumulation. We further show that rubble piles formed in a single disruption can have similar porosities but variable degrees of hydration. The direct formation of top shapes from single disruption alone can explain the relatively old crater-retention ages of the equatorial features of Ryugu and Bennu. Two separate parent-body disruptions are not necessarily required to explain their different hydration levels.

3.
Science ; 368(6491): 654-659, 2020 05 08.
Article in English | MEDLINE | ID: mdl-32381723

ABSTRACT

The near-Earth asteroid (162173) Ryugu is thought to be a primitive carbonaceous object that contains hydrated minerals and organic molecules. We report sample collection from Ryugu's surface by the Hayabusa2 spacecraft on 21 February 2019. Touchdown images and global observations of surface colors are used to investigate the stratigraphy of the surface around the sample location and across Ryugu. Latitudinal color variations suggest the reddening of exposed surface material by solar heating and/or space weathering. Immediately after touchdown, Hayabusa2's thrusters disturbed dark, fine grains that originate from the redder materials. The stratigraphic relationship between identified craters and the redder material indicates that surface reddening occurred over a short period of time. We suggest that Ryugu previously experienced an orbital excursion near the Sun.

4.
Nat Commun ; 10(1): 3247, 2019 07 19.
Article in English | MEDLINE | ID: mdl-31324761

ABSTRACT

Marine biogenic sulphur affects Earth's radiation budget and may be an indicator of primary productivity in the Southern Ocean, which is closely related to atmospheric CO2 variability through the biological pump. Previous ice-core studies in Antarctica show little climate dependence of marine biogenic sulphur emissions and hence primary productivity, contradictory to marine sediment records. Here we present new 720,000-year ice core records from Dome Fuji in East Antarctica and show that a large portion of non-sea-salt sulphate, which was traditionally used as a proxy for marine biogenic sulphate, likely originates from terrestrial dust during glacials. By correcting for this, we make a revised calculation of biogenic sulphate and find that its flux is reduced in glacial periods. Our results suggest reduced dimethylsulphide emissions in the Antarctic Zone of the Southern Ocean during glacials and provide new evidence for the coupling between climate and the Southern Ocean sulphur cycle.


Subject(s)
Ice Cover , Phytoplankton/metabolism , Seawater/chemistry , Sulfur/metabolism , Antarctic Regions , Atmosphere/chemistry , Carbon Dioxide/metabolism , Climate , Geography , Oceans and Seas , Sulfur Acids/metabolism , Temperature
5.
Science ; 364(6437): 268-272, 2019 04 19.
Article in English | MEDLINE | ID: mdl-30890588

ABSTRACT

The Hayabusa2 spacecraft arrived at the near-Earth carbonaceous asteroid 162173 Ryugu in 2018. We present Hayabusa2 observations of Ryugu's shape, mass, and geomorphology. Ryugu has an oblate "spinning top" shape, with a prominent circular equatorial ridge. Its bulk density, 1.19 ± 0.02 grams per cubic centimeter, indicates a high-porosity (>50%) interior. Large surface boulders suggest a rubble-pile structure. Surface slope analysis shows Ryugu's shape may have been produced from having once spun at twice the current rate. Coupled with the observed global material homogeneity, this suggests that Ryugu was reshaped by centrifugally induced deformation during a period of rapid rotation. From these remote-sensing investigations, we identified a suitable sample collection site on the equatorial ridge.

6.
Science ; 364(6437): 252, 2019 04 19.
Article in English | MEDLINE | ID: mdl-30890587

ABSTRACT

The near-Earth carbonaceous asteroid 162173 Ryugu is thought to have been produced from a parent body that contained water ice and organic molecules. The Hayabusa2 spacecraft has obtained global multicolor images of Ryugu. Geomorphological features present include a circum-equatorial ridge, east-west dichotomy, high boulder abundances across the entire surface, and impact craters. Age estimates from the craters indicate a resurfacing age of [Formula: see text] years for the top 1-meter layer. Ryugu is among the darkest known bodies in the Solar System. The high abundance and spectral properties of boulders are consistent with moderately dehydrated materials, analogous to thermally metamorphosed meteorites found on Earth. The general uniformity in color across Ryugu's surface supports partial dehydration due to internal heating of the asteroid's parent body.

7.
Nat Astron ; 3(4): 352-361, 2019 Apr.
Article in English | MEDLINE | ID: mdl-32601603

ABSTRACT

The top-shape morphology of asteroid (101955) Bennu is commonly found among fast-spinning asteroids and binary asteroid primaries, and might have contributed significantly to binary asteroid formation. Yet a detailed geophysical analysis of this morphology for a fast-spinning asteroid has not been possible prior to the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission. Combining the measured Bennu mass and shape obtained during the Preliminary Survey phase of OSIRIS-REx, we find a significant transition in Bennu's surface slopes within its rotational Roche lobe, defined as the region where material is energetically trapped to the surface. As the intersection of the rotational Roche lobe with Bennu's surface has been most recently migrating towards its equator (given Bennu's increasing spin rate), we infer that Bennu's surface slopes have been changing across its surface within the last million years. We also find evidence for substantial density heterogeneity within this body, suggesting that its interior has a distribution of voids and boulders. The presence of such heterogeneity and Bennu's top-shape is consistent with spin-induced failure at some point in its past, although the manner of its failure cannot be determined yet. Future measurements by the OSIRIS-REx spacecraft will give additional insights and may resolve questions regarding the formation and evolution of Bennu's top-shape morphology and its link to the formation of binary asteroids.

8.
J Eur Acad Dermatol Venereol ; 33(4): 753-760, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30520152

ABSTRACT

BACKGROUND: Trappin-2/pre-elafin is an endogenous inhibitor of human neutrophil elastase involved in inflammation, innate immunity and vascular remodelling, which consist of the complex pathological process of systemic sclerosis (SSc). OBJECTIVES: To clarify the potential role of trappin-2 in SSc. METHODS: Serum trappin-2 levels were determined by enzyme-linked immunosorbent assay in 51 SSc and 18 healthy subjects. Trappin-2 expression was evaluated in SSc lesional skin and cultured endothelial cells treated with FLI1 siRNA by immunohistochemistry, reverse transcription-real-time PCR and/or immunoblotting. Friend leukaemia virus integration 1 (Fli1) binding to the PI3 promoter was assessed by chromatin immunoprecipitation. RESULTS: Since serum trappin-2 levels inversely correlated with estimated glomerular filtration rate in SSc patients with renal dysfunction, SSc patients with normal renal function were analysed. Although serum trappin-2 levels were comparable between diffuse cutaneous SSc, limited cutaneous SSc and control subjects, the prevalence of digital ulcers or elevated right ventricular systolic pressure (RVSP) was significantly higher in SSc patients with elevated serum trappin-2 levels than in those with normal levels. Furthermore, serum trappin-2 levels were significantly increased in SSc patients with digital ulcers or elevated RVSP compared to those without. Moreover, serum trappin-2 levels positively correlated with RVSP values in SSc patients. Importantly, trappin-2 expression was enhanced in small vessels of SSc lesional skin. In cultured endothelial cells, trappin-2 expression was elevated by gene silencing of FLI1 at mRNA and protein levels and Fli1 occupied the PI3 promoter. CONCLUSIONS: Endothelial trappin-2 up-regulation partially due to Fli1 deficiency can be associated with the development of SSc vasculopathy.


Subject(s)
Elafin/blood , Scleroderma, Systemic/blood , Skin Ulcer/etiology , Ventricular Dysfunction, Right/etiology , Aged , Blood Pressure , Blood Vessels/metabolism , Case-Control Studies , Cells, Cultured , Endothelial Cells , Female , Gene Silencing , Humans , Male , Middle Aged , Proto-Oncogene Protein c-fli-1/genetics , Scleroderma, Systemic/complications , Scleroderma, Systemic/genetics , Skin/blood supply , Skin Ulcer/blood , Systole , Up-Regulation , Ventricular Dysfunction, Right/blood
9.
Nat Commun ; 9(1): 1476, 2018 04 16.
Article in English | MEDLINE | ID: mdl-29662058

ABSTRACT

The Northern Hemisphere experienced dramatic changes during the last glacial, featuring vast ice sheets and abrupt climate events, while high northern latitudes during the last interglacial (Eemian) were warmer than today. Here we use high-resolution aerosol records from the Greenland NEEM ice core to reconstruct the environmental alterations in aerosol source regions accompanying these changes. Separating source and transport effects, we find strongly reduced terrestrial biogenic emissions during glacial times reflecting net loss of vegetated area in North America. Rapid climate changes during the glacial have little effect on terrestrial biogenic aerosol emissions. A strong increase in terrestrial dust emissions during the coldest intervals indicates higher aridity and dust storm activity in East Asian deserts. Glacial sea salt aerosol emissions in the North Atlantic region increase only moderately (50%), likely due to sea ice expansion. Lower aerosol concentrations in Eemian ice compared to the Holocene are mainly due to shortened atmospheric residence time, while emissions changed little.

10.
Allergy ; 73(5): 1110-1118, 2018 05.
Article in English | MEDLINE | ID: mdl-29197099

ABSTRACT

BACKGROUND: Reducing near-fatal asthma exacerbations is a critical problem in asthma management. OBJECTIVES: To determine patterns of factors preceding asthma exacerbations in a real-world setting. METHODS: In a nationwide prospective study of 190 patients who had experienced near-fatal asthma exacerbation, cluster analysis was performed using asthma symptoms over the 2-week period before admission. RESULTS: Three distinct clusters of symptoms were defined employing the self-reporting of a visual analogue scale. Cluster A (42.1%): rapid worsening within 7.4 hours from moderate attack to admission, young to middle-aged patients with low Body mass index and tendency to depression who had stopped anti-asthma medications, smoked, and hypersensitive to environmental triggers and furred pets. Cluster B (40.0%): fairly rapid worsening within 48 hours, mostly middle-aged and older, relatively good inhaled corticosteroid (ICS) or ICS/long-acting beta-agonist (LABA) compliance, and low perception of dyspnea. Cluster C (17.9%): slow worsening over 10 days before admission, high perception of dyspnea, smokers, and chronic daily mild-moderate symptoms. There were no differences in overuse of short-acting beta-agonists, baseline asthma severity, or outcomes after admission for patients in these 3 clusters. CONCLUSION: To reduce severe or life-threatening asthma exacerbation, personalized asthma management plans should be considered for each cluster. Improvement of ICS and ICS/LABA compliance and cessation of smoking are important in cluster A. To compensate for low perception of dyspnea, asthma monitoring of peak expiratory flow rate and/or exhaled nitric oxide would be useful for patients in cluster B. Avoidance of environmental triggers, increase usual therapy, or new anti-type 2 response-targeted therapies should be considered for cluster C.


Subject(s)
Asthma/diagnosis , Asthma/epidemiology , Asthma/etiology , Adult , Cluster Analysis , Female , Humans , Japan/epidemiology , Male , Middle Aged , Prospective Studies , Risk Factors , Surveys and Questionnaires
11.
J Eur Acad Dermatol Venereol ; 32(2): 291-297, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28681537

ABSTRACT

BACKGROUND: Antimicrobial peptides have attracted much attention as a member of disease-associated molecules in systemic sclerosis (SSc), which is pathologically characterized by immune abnormalities, vasculopathy and tissue fibrosis. OBJECTIVE: To investigate the potential contribution of one of the antimicrobial peptide psoriasin to the development of SSc. METHODS: Psoriasin expression in the skin samples and sera derived from SSc patients and its correlation with clinical parameters were analysed. Psoriasin expression was evaluated by immunohistochemistry with skin samples from SSc patients and healthy controls. Serum levels of psoriasin were determined by enzyme-linked immunosorbent assay in 51 SSc patients and 19 healthy controls and assessed for the association with clinical symptoms. RESULTS: The expression of psoriasin was elevated in the epidermis of SSc lesional skin. Serum psoriasin levels were higher in SSc patients, especially in diffuse cutaneous SSc patients with disease duration of <6 years, than in healthy controls. With respect to clinical association, SSc patients with interstitial lung disease, telangiectasia and pitting scars had significantly augmented levels of serum psoriasin than those without each of these symptoms. In the subgroup of patients with interstitial lung disease, the elevation of serum psoriasin levels was associated with higher ground-glass opacity scores. Furthermore, serum psoriasin levels were decreased after the treatment with intravenous cyclophosphamide pulse as compared to baseline values. CONCLUSION: Our findings indicate a possible contribution of psoriasin to the development of clinical symptoms associated with vascular and epithelial abnormalities and inflammation in SSc, further supporting the roles of antimicrobial peptides in the SSc pathogenesis.


Subject(s)
Cicatrix/blood , Lung Diseases, Interstitial/blood , S100 Calcium Binding Protein A7/blood , Scleroderma, Systemic/blood , Telangiectasis/blood , Adult , Aged , Case-Control Studies , Cicatrix/etiology , Cyclophosphamide/therapeutic use , Female , Humans , Immunosuppressive Agents/therapeutic use , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/etiology , Male , Middle Aged , Radiography, Thoracic , S100 Calcium Binding Protein A7/metabolism , Scleroderma, Systemic/complications , Scleroderma, Systemic/drug therapy , Scleroderma, Systemic/metabolism , Skin/metabolism , Telangiectasis/etiology
12.
J Neuroendocrinol ; 29(6)2017 06.
Article in English | MEDLINE | ID: mdl-28475285

ABSTRACT

Pulsatile secretion of gonadotrophin-releasing hormone (GnRH)/luteinising hormone is indispensable for the onset of puberty and reproductive activities at adulthood in mammalian species. A cohort of neurones expressing three neuropeptides, namely kisspeptin, encoded by the Kiss1 gene, neurokinin B (NKB) and dynorphin A, localised in the hypothalamic arcuate nucleus (ARC), so-called KNDy neurones, comprises a putative intrinsic source of the GnRH pulse generator. Synchronous activity among KNDy neurones is considered to be required for pulsatile GnRH secretion. It has been reported that gap junctions play a key role in synchronising electrical activity in the central nervous system. Thus, we hypothesised that gap junctions are involved in the synchronised activities of KNDy neurones, which is induced by NKB-NK3R signalling. We determined the role of NKB-NK3R signalling in Ca2+ oscillation (an indicator of neuronal activities) of KNDy neurones and its synchronisation mechanism among KNDy neurones. Senktide, a selective agonist for NK3R, increased the frequency of Ca2+ oscillations in cultured Kiss1-GFP cells collected from the mediobasal hypothalamus of the foetal Kiss1-green fluorescent protein (GFP) mice. The senktide-induced Ca2+ oscillations were synchronised in the Kiss1-GFP and neighbouring glial cells. Confocal microscopy analysis of these cells, which have shown synchronised Ca2+ oscillations, revealed close contacts between Kiss1-GFP cells, as well as between Kiss1-GFP cells and glial cells. Dye coupling experiments suggest cell-to-cell communication through gap junctions between Kiss1-GFP cells and neighbouring glial cells. Connexin-26 and -37 mRNA were found in isolated ARC Kiss1 cells taken from adult female Kiss1-GFP transgenic mice. Furthermore, 18ß-glycyrrhetinic acids and mefloquine, which are gap junction inhibitors, attenuated senktide-induced Ca2+ oscillations in Kiss1-GFP cells. Taken together, these results suggest that NKB-NK3R signalling enhances synchronised activities among neighbouring KNDy neurones, and that both neurone-neurone and neurone-glia communications via gap junctions possibly contribute to synchronised activities among KNDy neurones.


Subject(s)
Gap Junctions/physiology , Neuroglia/physiology , Neurons/physiology , Peptide Fragments/pharmacology , Substance P/analogs & derivatives , Animals , Cells, Cultured , Connexins/metabolism , Dynorphins/physiology , Gap Junctions/drug effects , Gap Junctions/metabolism , Glycyrrhetinic Acid/analogs & derivatives , Glycyrrhetinic Acid/pharmacology , Kisspeptins/genetics , Medulla Oblongata/metabolism , Mefloquine/pharmacology , Mice, Transgenic , Neuroglia/metabolism , Neurokinin B/physiology , Neurons/drug effects , Neurons/metabolism , Peptide Fragments/antagonists & inhibitors , Substance P/antagonists & inhibitors , Substance P/pharmacology
14.
J Neuroendocrinol ; 28(10)2016 10.
Article in English | MEDLINE | ID: mdl-27344056

ABSTRACT

Rodents show apparent sex differences in their sexual behaviours. The present study used Kiss1 knockout (KO) rats to evaluate the role of kisspeptin in the defeminisation/masculinisation of the brain mechanism that controls sexual behaviours. Castrated adult Kiss1 KO males treated with testosterone showed no male sexual behaviours but demonstrated the oestrogen-induced lordosis behaviours found in wild-type females. The sizes of some of the sexual dimorphic nuclei of Kiss1 KO male rats are similar to those of females. Plasma testosterone levels at embryonic day 18 and postnatal day 0 (PND0) in Kiss1 KO males were high, similar to wild-type males, indicating that perinatal testosterone is secreted in a kisspeptin-independent manner. Long-term exposure to testosterone from peripubertal to adult periods restored mounts and intromissions in KO males, suggesting that kisspeptin-dependent peripubertal testosterone secretion is required to masculinise the brain mechanism. This long-term testosterone treatment failed to abolish lordosis behaviours in KO males, whereas kisspeptin replacement at PND0 reduced lordosis quotients in Kiss1 KO males but not in KO females. These results suggest that kisspeptin itself is required to defeminise behaviour in the perinatal period, in cooperation with testosterone. Oestradiol benzoate treatment at PND0 suppressed lordosis quotients in Kiss1 KO rats, indicating that the mechanisms downstream of oestradiol work properly in the absence of kisspeptin. There was no significant difference in aromatase gene expression in the whole hypothalamus between Kiss1 KO and wild-type male rats at PND0. Taken together, the present study demonstrates that both perinatal kisspeptin and kisspeptin-independent testosterone are required for defeminisation of the brain, whereas kisspeptin-dependent testosterone during peripuberty to adulthood is needed for masculinisation of the brain in male rats.


Subject(s)
Brain/physiology , Kisspeptins/physiology , Sex Differentiation , Testosterone/physiology , Animals , Animals, Newborn , Brain/drug effects , Castration , Female , Gene Knockout Techniques , Kisspeptins/genetics , Male , Sex Characteristics , Sex Differentiation/drug effects , Sexual Behavior, Animal , Testosterone/administration & dosage , Testosterone/blood
15.
Clin Exp Allergy ; 46(8): 1043-55, 2016 08.
Article in English | MEDLINE | ID: mdl-27041475

ABSTRACT

BACKGROUND: Severe or life-threatening asthma exacerbation is one of the worst outcomes of asthma because of the risk of death. To date, few studies have explored the potential heterogeneity of this condition. OBJECTIVES: To examine the clinical characteristics and heterogeneity of patients with severe or life-threatening asthma exacerbation. METHODS: This was a multicentre, prospective study of patients with severe or life-threatening asthma exacerbation and pulse oxygen saturation < 90% who were admitted to 17 institutions across Japan. Cluster analysis was performed using variables from patient- and physician-orientated structured questionnaires. RESULTS: Analysis of data from 175 patients with severe or life-threatening asthma exacerbation revealed five distinct clusters. Cluster 1 (n = 27) was younger-onset asthma with severe symptoms at baseline, including limitation of activities, a higher frequency of treatment with oral corticosteroids and short-acting beta-agonists, and a higher frequency of asthma hospitalizations in the past year. Cluster 2 (n = 35) was predominantly composed of elderly females, with the highest frequency of comorbid, chronic hyperplastic rhinosinusitis/nasal polyposis, and a long disease duration. Cluster 3 (n = 40) was allergic asthma without inhaled corticosteroid use at baseline. Patients in this cluster had a higher frequency of atopy, including allergic rhinitis and furred pet hypersensitivity, and a better prognosis during hospitalization compared with the other clusters. Cluster 4 (n = 34) was characterized by elderly males with concomitant chronic obstructive pulmonary disease (COPD). Although cluster 5 (n = 39) had very mild symptoms at baseline according to the patient questionnaires, 41% had previously been hospitalized for asthma. CONCLUSIONS & CLINICAL RELEVANCE: This study demonstrated that significant heterogeneity exists among patients with severe or life-threatening asthma exacerbation. Differences were observed in the severity of asthma symptoms and use of inhaled corticosteroids at baseline, and the presence of comorbid COPD. These findings may contribute to a deeper understanding and better management of this patient population.


Subject(s)
Asthma/diagnosis , Asthma/epidemiology , Adult , Aged , Asthma/therapy , Cluster Analysis , Comorbidity , Disease Progression , Female , Hospitalization , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Phenotype , Prospective Studies , Risk Factors , Severity of Illness Index , Surveys and Questionnaires
16.
Zygote ; 24(1): 115-20, 2016 Feb.
Article in English | MEDLINE | ID: mdl-25732862

ABSTRACT

We have recently reported that multiple aster formation after in vitro fertilization (IVF) was one of the factors that negatively affected the developmental competence of vitrified-warmed bovine matured oocytes, and that short-term culture of the post-warm oocytes with an inhibitor of Rho-associated coiled-coil kinase (ROCK) suppressed the multiple aster formation and improved the blastocyst yield. The present study was conducted to investigate whether increased multiple aster formation following IVF was involved in impaired developmental competence of stored ovary-derived bovine oocytes. Oocytes retrieved from 1-day stored ovaries had lower developmental potential to day 8 blastocysts when compared with those from fresh ovaries (37 versus 63%). Immunostaining of α-tubulin 10 h post-IVF revealed that a higher incidence of multiple aster formation occurred in oocytes retrieved from stored ovaries than from fresh ovaries (31 versus 15%). Treatment of post-in vitro maturated (post-IVM) oocytes with ROCK inhibitor for 2 h significantly suppressed the incidence of multiple aster formation (10 versus 32% in the control group). However, the suppression effect of ROCK inhibitor on multiple aster formation in IVM/IVF oocytes did not improve blastocyst yield from stored ovary-derived oocytes (41 versus 37% in the control group). These results suggested that the higher incidence of multiple aster formation by bovine ovary storage was not responsible for the decreased developmental competence of IVF oocytes.


Subject(s)
Oocyte Retrieval/methods , Oocytes/cytology , Oocytes/physiology , Ovary/cytology , Amides/pharmacology , Animals , Blastocyst/physiology , Cattle , Enzyme Inhibitors/pharmacology , Female , Fertilization in Vitro/methods , In Vitro Oocyte Maturation Techniques , Oocytes/drug effects , Pyridines/pharmacology , rho-Associated Kinases/antagonists & inhibitors
17.
J Neuroendocrinol ; 27(3): 187-97, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25582792

ABSTRACT

Kisspeptin, encoded by the Kiss1 gene, has attracted attention as a key candidate neuropeptide in controlling puberty and reproduction via regulation of gonadotrophin-releasing hormone (GnRH) secretion in mammals. Pioneer studies with Kiss1 or its cognate receptor Gpr54 knockout (KO) mice showed the indispensable role of kisspeptin-GPR54 signalling in the control of animal reproduction, although detailed analyses of gonadotrophin secretion, especially pulsatile and surge-mode of luteinising hormone (LH) secretion, were limited. Thus, in the present study, we have generated Kiss1 KO rats aiming to evaluate a key role of kisspeptin in governing reproduction via pulse and surge modes of GnRH/LH secretion. Kiss1 KO male and female rats showed a complete suppression of pulsatile LH secretion, which is responsible for folliculogenesis and spermatogenesis, and an absence of puberty and atrophic gonads. Kiss1 KO female rats showed no spontaneous LH/follicle-stimulating hormone surge and an oestrogen-induced LH surge, suggesting that the GnRH surge generation system, which is responsible for ovulation, does not function without kisspeptin. Furthermore, challenge of major stimulatory neurotransmitters, such as monosodium glutamate, NMDA and norepinephrine, failed to stimulate LH secretion in Kiss1 KO rats, albeit they stimulated LH release in wild-type controls. Taken together, the results of the present study confirm that kisspeptin plays an indispensable role in generating two modes (pulse and surge) of GnRH/gonadotrophin secretion to regulate puberty onset and normal reproductive performance. In addition, the present study suggests that kisspeptin neurones play a critical role as a hub integrating major stimulatory neural inputs to GnRH neurones, using newly established Kiss1 KO rats, which serve as a useful model for detailed analysis of hormonal profiles.


Subject(s)
Glutamic Acid/physiology , Kisspeptins/physiology , Luteinizing Hormone/metabolism , Sexual Maturation/physiology , Animals , Female , Follicle Stimulating Hormone/metabolism , Kisspeptins/genetics , Male , Mice, Knockout , N-Methylaspartate/physiology , Norepinephrine/physiology , Rats , Sexual Maturation/genetics
18.
Zygote ; 22(4): 476-82, 2014 Nov.
Article in English | MEDLINE | ID: mdl-23731802

ABSTRACT

Although vitrification is a useful technique for preservation of bovine oocytes, the yield of blastocysts derived from the vitrified oocytes is still low. We have recently reported a new type of cryoinjury, multiple aster formation, by which pronuclear migration and development of vitrified-warmed and in vitro-fertilized bovine oocytes are impaired. The aim of the present study was to investigate the effect of glutathione (GSH) content of vitrified bovine oocytes on multiple aster formation and subsequent in vitro development. Treatment of bovine cumulus-oocyte complexes with ß-mercaptoethanol (ßME) and L-cysteine (Cys) during in vitro maturation resulted in 2.5-fold higher GSH content not only in fresh control but also in vitrified-warmed oocytes. The percentage of normally fertilized zygotes exhibiting sperm aster(s) was >95% in all four groups (with or without ßME/Cys × fresh control or vitrified). The frequency of multiple aster formation in vitrified oocytes (three-fold higher than that in fresh control oocytes) was not affected by the increased level of intracellular GSH with ßME/Cys. Consequently, the migration and development of pronuclei as well as the yield of blastocysts from vitrified-warmed oocytes (17 versus 41%) were not improved. In addition, there was no effect of increased GSH level on the yield of blastocysts in fresh control groups.


Subject(s)
Blastocyst/physiology , Glutathione/metabolism , Microtubules/metabolism , Oocytes/physiology , Animals , Cattle , Cryopreservation/methods , Cysteine/pharmacology , Female , Fertilization in Vitro/methods , Mercaptoethanol/pharmacology , Oocytes/cytology , Oocytes/drug effects , Vitrification , Zygote
19.
Theriogenology ; 77(5): 908-15, 2012 Mar 15.
Article in English | MEDLINE | ID: mdl-22115806

ABSTRACT

In vitro-matured bovine oocytes do not tolerate vitrification as well as mature murine or human oocytes. Delayed first cleavage in vitrified and in vitro-fertilized bovine oocytes may be responsible for the decreased yield of blastocysts in vitro. Because formation of sperm-aster and the subsequent assembly of microtubule network play an important role for migration and fusion of both pronuclei, aster formation in vitrified-warmed oocytes was analyzed by confocal laser-scanning microscopy. At 10 h post-insemination (hpi), proportions of oocytes fertilized normally were comparable between the vitrified and fresh control groups (67 and 70%, respectively). Proportions of oocytes that exhibited microtubule assembly were similar between the two groups (95% each), but the proportion of oocytes with multiple asters was higher in the vitrified group when compared with the fresh control group (68 vs 29%, P < 0.05). Both migration and development of two pronuclei were adversely affected by multiple aster formation. In the next experiment, multiple asters observed in 5.5 vs 8 hpi pronuclear zygotes were located near the male pronucleus, suggesting that those multiple asters were not the cytoplasmic asters of maternal origin. In conclusion, multiple aster formation frequently observed in vitrified-warmed bovine oocytes may be related to loss of ooplasmic function responsible for normal microtubule assembly from the sperm-aster.


Subject(s)
Cattle , Cryopreservation/veterinary , Fertilization in Vitro/veterinary , Hot Temperature , Oocytes/ultrastructure , Spermatozoa/diagnostic imaging , Animals , Blastocyst/physiology , Cleavage Stage, Ovum , Female , Fertilization , Male , Microtubule-Organizing Center/ultrastructure , Microtubules/physiology , Microtubules/ultrastructure , Tubulin/chemistry , Ultrasonography , Vitrification , Zygote/ultrastructure
20.
Theriogenology ; 74(6): 1028-35, 2010 Oct 01.
Article in English | MEDLINE | ID: mdl-20580073

ABSTRACT

The objective was to investigate the effects of developmental stage (fully-expanded or expanding blastocysts) and/or age (harvested on Days 7 or 8) on post-vitrification in vitro survival of bovine blastocysts derived from intracytoplasmic sperm injection (ICSI) or in vitro fertilization (IVF). Post-warming survival (re-expansion of blastocoele within 24 h) of ICSI-derived fully-expanded blastocysts (80%) was similar to that of their IVF-derived counterparts (88%). However, the ability of ICSI-derived expanding blastocysts to survive vitrification procedures (61%) was lower than that of IVF-derived blastocysts (85%; P < 0.05), although the ICSI- and IVF-derived fresh blastocysts were of similar quality. The age of the blastocysts before vitrification did not affect cryotolerance for either ICSI-derived (73 and 59% for Days 7 and 8 embryos, respectively) or IVF-derived blastocysts (86% for both Days 7 and 8 embryos). At 24 h of post-warming culture, ICSI-derived blastocysts surviving vitrification contained a higher proportion of dead cells than their IVF-derived counterparts (5-13% vs. 2-4%; P < 0.05), but these proportions were not different from those of fresh control embryos. There was an adverse effect of vitrification on the ability of blastocysts to hatch within 72 h of culture only in IVF-derived Day 8 blastocysts (41 and 70% in vitrified and fresh control groups, respectively). In conclusion, the proportion of blastocysts that survived vitrification procedures was similar for ICSI- and IVF-derived bovine blastocysts if the former were cultured to the fully-expanded stage prior to vitrification, with no significant difference between embryos harvested on Day 7 versus Day 8.


Subject(s)
Blastocyst , Cattle , Cleavage Stage, Ovum/physiology , Cryopreservation/methods , Embryonic Development/physiology , Animals , Cattle/physiology , Cell Size , Cell Survival , Cells, Cultured , Cryopreservation/veterinary , Embryo Culture Techniques/veterinary , Female , Fertilization in Vitro/methods , Fertilization in Vitro/veterinary , Gestational Age , Male , Quality Control , Sperm Injections, Intracytoplasmic/methods , Sperm Injections, Intracytoplasmic/veterinary , Temperature
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