Human Reproduction Open
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2025
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IF 11.1
Li Zhibin,Li Shuying,Xiao Yufeng,Guo Junfeng,Zhou Jianchun,Chen Yang,Yang Juan,Gong Chunli,He Bing,Wu Yuyun,Gao Nannan,Yang Huan,Gao Limin,Hu Hua,Zhang Yunfang,Yang Shiming
What are the molecular mechanisms underlying hypoxia-induced male reproductive impairment?Hypoxia compromises Septin2 (Sept2) transcription in spermatogonia, which impedes spermatogonial proliferation through protein phosphatase 2A (PP2A)-dependent AKT dephosphorylation.Hypoxia is associated with impaired spermatogenesis and poor sperm parameters in men. Spermatogonia proliferation, a crucial early step in spermatogenesis, is essential for maintaining the spermatogenic cell population and ensuring sperm quality. However, the connection between hypoxia and spermatogonial proliferation remains poorly understood, and treatment options for hypoxia-related reproductive disorders are limited.A cross-sectional study analyzed semen samples from 24 high-altitude (HA) residents, 6 pathological hypoxia (PH) patients, and 19 healthy controls to evaluate hypoxia-associated sperm parameter alterations. Complementary animal studies employing a hypobaric chamber-induced hypoxic mouse model (n = 5) confirmed reproductive impairments through assessment of birth rates, sperm quality, and testicular histopathology. Transcriptomic profiling of hypoxic versus normoxic mouse testes (n = 3/group) identified spermatogonial proliferation defects as a predominant pathological feature and pinpointed Sept2 as a candidate mediator. Subsequent mechanistic investigations employed in vitro hypoxic culture of spermatogonial cell lines under hypoxic conditions coupled with pharmacological modulation of PP2A activity in mice (n = 3-5 per intervention group) to delineate the underlying molecular pathways.Semen parameters were evaluated using computer-assisted sperm analysis (CASA; for sperm concentration, count, and motility), morphological staining (Pap staining for sperm deformity), and eosin-nigrosin staining (for sperm viability). In hypoxic mouse model, fertility outcomes were assessed through fertility assessment (mating experiments), sperm parameters (CASA), testicular histology (H&E staining), and spermatogonia proliferation (immunohistochemistry and qPCR). In hypoxic spermatogonial cell models, cell proliferation was detected using CCK-8, EdU incorporation, flow cytometry, and western blotting. Sept2 manipulation (knockdown/overexpression), followed by mechanistic analyses (dual-luciferase reporter assay, DNA pulldown/mass spectrometry, TMT-based quantitative proteomics, co-immunoprecipitation, etc), was performed to investigate the mechanism underlying hypoxia-regulated spermatogonia proliferation. The SEPT2 inhibitor forchlorfenuron (FCF), the PP2A agonists celastrol, erlotinib, and FTY720, as well as PP2A inhibitor okadaic acid (OA) were used to investigate the role of the SEPT2-PP2A-AKT axis in male fertility regulation.Both human populations (HA residents and PH patients) and mouse model consistently demonstrated hypoxia-related reproductive dysfunction. Mechanistic analyses revealed that hypoxia significantly downregulated Sept2 expression in spermatogonia, concomitant with impaired proliferative capacity. Sept2 knockdown in normoxic mice the hypoxia-induced defects in spermatogenesis. Complementary in vitro studies confirmed that Sept2 depletion impaired spermatogonial proliferation by inducing G1-S phase arrest, while its overexpression mitigated hypoxia-related proliferative defects. Further investigation revealed that hypoxia disrupts Sept2 transcription by interfering with the binding of RNA polymerase II subunit A (POLR2A) to the Sept2 promoter. The consequent reduction in Sept2 expression led to stabilization of the B56γ regulatory subunit of PP2A, resulting in enhanced AKT dephosphorylation and subsequent suppressed proliferation. Pharmacological intervention with the PP2A inhibitor OA restored reproductive competence and sperm quality in hypoxic mice, whereas PP2A agonists exacerbated these deficits.RNA-seq data are deposited in China National Center for Bioinformation (CNCB) under accession number PRJCA035733.This study focused on the effects of hypoxia on sperm parameters. Additional factors such as alterations in reproductive hormones and sexual function may contribute to hypoxia-induced infertility and warrant further research.This study identifies the SEPT2-PP2A/B56γ-AKT axis as a key regulator in hypoxia-related spermatogonia proliferation impairment. PP2A inhibitors such as OA may offer a therapeutic strategy to protect male fertility under hypoxic conditions.This work was supported by the National Natural Science Foundation of China (No. 82101688) and Natural Science Foundation of Chongqing (No. CSTB2022NSCQ-MSX0943). The authors have no conflicts of interest to declare.
研究领域:
生殖生物学
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分子生物学
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医学
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PubMed
高影响因子
CABI Agriculture & Bioscience
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2023
·Vol. 4
·期 1
·1-8
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IF 3.9
Huang Hexi,Di Ning,Wang Jie,Wang Yuxing,Zhu Zhengyang,Lu Caige,Wang Su,Zang Liansheng
The heavy metal, cadmium (Cd), causing growth retardation and yield reduction on rice and impacting the fitness of organisms inhabiting on rice through bottom-up effects, has become a great challenge to rice production. However, the effect of Cd-exposure on the development of an economically important and destructive rice pest, Chilo suppressalis remains unexplored. By exposing the larvae of C. suppressalis to different Cd-exposed artificial diets (0, 0.2, 1.0, 2.5, 5.0, and 10.0 mg/kg), we found that Cd exposure did not affect the larval duration or pupation rate of C. suppressalis , but caused negative effects on pupal weight at high Cd levels (5.0 and 10.0 mg/kg) and on adult deformity rate from 2.5 and 5.0 mg/kg treatments. Although Cd significantly increased the female pupae ratio, C. suppressalis did not oviposit when Cd treatment was more than 2.5 mg/kg. Meanwhile, Cd transferred to pupae, females, exuviae of pupa and eggs of C. suppressalis from Cd treated larvae, and exhibited a dose-dependent response on Cd accumulation. Our results indicated that Cd had a negative effect on rice stem borer and can be transferred to eggs of C. suppressalis , but more work is needed to further assess the bottom-up effect on third tropic levels in Cd-polluted fields.
研究领域:
生态毒理学
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昆虫学
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高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2023
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IF 4.7
Shaoquan Liu,Jianlu Zhang,Ruijiao Li,Chunyun Zhang,Lixin Wang,Hao Liang,Guangpeng Feng,Dongmei Xiong
Due to chemical and photochemical stability, triazophos has been frequently detected in rivers and oceans over the years with extensive use for pest control in agriculture , and it has become a worldwide ecological concern to the aquatic environment . Until now, fewer data are available regarding the potential long-term adverse effects of triazophos on aquatic invertebrates , which plays an essential role in aquatic food webs , as a key group for water ecosystems. In this experiment, the F 1 - and F 2 progenies of Daphnia magna were recovered when daphnias (F 0 ) exposure to triazophos at environmental-related concentrations (0.1 and 1.0 μg/L) for 21 d; and the indexes related to phenotypic traits, reproduction and gene expression were measured in tested animals. The results showed that heart rate and total number of neonates in exposed F 0 -daphnias were significantly lower than those of control group, and the detoxification genes ( HR96 and P-gp ) were up-regulated while genes related reproduction ( Vtg ) and molting ( Nvd and Shd ) were significantly down-regulated. The heart rate and individual size of F 1 -daphnias (<24 h) were significantly reduced in the treatment group. After 21-d recovery, the heart rate and expression of HR96 , P-gp, Vtg, Nvd and Shd were declined in F 1 -daphnias. There was no obvious difference of morphological traits and heart rate between treatment and control in F 2 -daphnias (<24 h). In summary, daphnias (F 0 ) exposure to triazophos with environmental dose could raise toxic effects on its offspring (F 1 ), which is mainly manifested by reduced heart rate, the accumulated number and individual size of offspring and decreased expression of genes related to molting and reproduction.
研究领域:
环境毒理学
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水生生态学
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高影响因子
BULLETIN OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY
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2024
·Vol. 114
·期 1
·1-8
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IF 2.7
Wang Jun,Li Meng,Gu Lei,Sun Yunfei,Zhu Xuexia,Yang Zhou
Atrazine is a predominant herbicide globally, and its residues are commonly found in natural water bodies due to its extensive use. Atrazine is known for its detrimental effects on the reproductive abilities of aquatic plants and animals. Our study explored the impact of maternal exposure to atrazine on the survival and performance of offspring using the water flea Daphnia magna as a model organism. We investigated how the life-history traits and population dynamics of maternal D. magna and their offspring are influenced by atrazine. We hypothesized that exposure to atrazine in mothers would negatively affect the survival and performance of their offspring. The findings revealed that short-term exposure to atrazine adversely affects fitness-related traits, manifesting as decreased survivorship and reduced fecundity. Offspring from atrazine-exposed mothers displayed a limited recovery in fitness; no mortality was observed during the 14-day experiment, yet fecundity remained significantly reduced. At the population level, maternal exposure to atrazine led to a decreased population carrying capacity. The notable maternal effects on offspring reproduction underscore the long-term toxicity of atrazine to D. magna populations, suggesting prolonged consequences even after the cessation of atrazine pollution. This study underscores the transgenerational effects of atrazine, highlighting its persistent threat to D. magna populations.
研究领域:
生态毒理学
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环境科学
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高影响因子
ENVIRONMENTAL POLLUTION
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2024
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IF 7.6
Jingjing Du,Tianying Tao,Mengxi Gao,Xueting Zhang,Xilin Wang,Qian Zhang,Yuanqian Xu,Baodan Jin,Lan Wang,Xia Cao
Nanoplastics pose a potential threat to a wide variety of aquatic organisms . Despite the awareness of this existing hazard, the impact of nanoplastics on natural fungal communities remains a research gap. In this study, five dominant fungi species, isolated from a stream ecosystem, were used to explore the effects of different nano-polystyrene (nano-PS) particles concentrations on a simulated fungal community. Specifically, the evaluation was conducted regarding the fungal growth , reproductivity, structural composition, and ecological function in leaf litter decomposition. A 15-day exposure experiment showed that 100 μg/L nano-PS significantly reduced the microcosm pH. The extracellular enzyme activities of β-glucosidase, leucine-aminopeptidase, and peroxidase were significantly promoted by nano-PS exposure for 5 days or 15 days. Total sporulation rate significantly decreased after the 15-day exposure to 1 and 100 μg/L nano-PS and significantly increased under 10 μg/L nano-PS. In contrast, nano-PS concentrations had no effects on fungal biomass . In addition, the reduced relative abundance of Geotrichum candidum lowered its contribution to leaf decomposition, resulting in a decreased litter decomposition rate of a 24.5–27.9 % after exposure. This suggests that 1–100 μg/L nano-PS inhibited leaf decomposition by inhibiting fungal reproduction and reducing the contribution of specific fungal species. In addition, the findings highlight the importance of exploring the potential mechanisms of the interaction between nanoplastics and fungal species.
研究领域:
生态学
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环境科学
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高影响因子
Algal Research-Biomass Biofuels and Bioproducts
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2017
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IF 3.994
Guang Gao,Anthony S. Clare,Craig Rose,Gary S. Caldwell
Periodic biomass losses caused by reproduction have greatly limited the expansion of the land-based cultivation of the seaweed Ulva . In an attempt to resolve this, we obtained a sterile mutant (SM) of U. rigida by mutating a wild type (WT) strain using ultraviolet radiation (UVC). The SM grew five times faster than the WT with 40.0% and 30.9% higher nitrate and phosphate uptake rates. Crucially, the SM remained in the vegetative state throughout the 27-day trial, unlike the WT. The lipid content was more than double that of the WT with more monounsaturated, polyunsaturated, omega-3 and omega-6 fatty acids but with a 26.3% lower protein content. The swelling, water holding, and oil holding capacities were all lower than the WT. The rapidly growing SM showed distinct promise for application to carbon capture and wastewater bioremediation and for more conventional aquaculture practices. Despite some modified nutritional and functional properties, the SM still retained a desirable nutritional profile.
研究领域:
海洋生物学
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环境科学
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生物技术
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高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2020
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IF 6.551
Dong Sun,Qi Chen,Bo Zhu,Hui Zhao,Shunshan Duan
Nonylphenol (NP) is a toxic xenobiotic compound, which is persistent in the aquatic environment and is extremely toxic to aquatic organisms. Although the exact molecular mechanisms of its toxic effect are well understood, the multigenerational reproduction and multigenerational - gene expression changes caused by NP still remain unclear. The following work investigated the effect of NP on four consecutive generations of zebrafish by examining their growth and several reproductive parameters, the degree of gonad damage, and the expression of related reproduction related genes. The results showed that high concentrations (20 and 200 μg·L −1 ) of NP could decrease growth and induce gonad damage in zebrafish. In addition, gnrh2 and gnrh3 genes were up-regulated, and fshβ and lhβ genes were downregulated in the hypothalamus in male zebrafish; while in female fish, the fshβ and lhβ were upregulated in P and F1 generations, and then down-regulated in the F2 generation. Meanwhile, the cyp19a1a gene was downregulated in the gonad of male fish, while the genes of fshr , lhr and esr showed a downward trend in females. Compared to P generation, F2 generation was more tolerant to higher NP concentrations (20 and 200 μg·L −1 ), as was also more sensitive to lower concentrations of NP (2 μg·L −1 ). Consequently, stress and damage caused by environmentally-relevant concentrations of aquatic pollutants in a vertebrate model were measured and predicted. Prevention and control measures can be actively and effectively proposed, which might be transversal to other exposed organisms, including humans. After several generations, typical transgenerational genetic phenomena might occur, which should be addressed by further studies.
研究领域:
环境科学
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毒理学
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分子生物学
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PubMed
高影响因子
PEST MANAGEMENT SCIENCE
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2019
·Vol. 76
·期 3
·888-893
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IF 3.255
Kipchoge Leviticus,Li Cui,Han Ling,Zhong-Qiang Jia,Qiu-Tang Huang,Zhao-Jun Han,Chun-Qing Zhao,Lu Xu
BACKGROUND Two-spotted spider mite (TSSM), Tetranychus urticae Koch is a serious agricultural pest and has developed high levels of resistance to many acaricides. Hence, screening new acaricides is important in the control of TSSM. Fluralaner, a novel isoxazoline, has high activity against agricultural and ectoparasitic pests; however, little information is available about its effects on agricultural mites. Lethal and sublethal effects of fluralaner towards TSSM eggs and female adults were therefore evaluated in this study. RESULTS Fluralaner exhibited higher activity towards TSSM female adults (LC 50 , 0.49 mg L −1 ) compared with commercial acaricides including fenpyroximate, pyridaben and hexythiazox, and also excellent activity towards eggs (LC 50 , 0.36 mg L −1 ). The results of a sublethal effect study showed a significant reduction in the duration and fecundity of female adults with increases in the tested concentrations. The net reproductive rate ( R 0 ) decreased to 67.34 ± 3.96 and 50.29 ± 3.40 offspring per individual in LC 10 and LC 30 treatments compared with control (108.31 ± 7.61 offspring per individual). The intrinsic rate of increase ( r ) and finite rate of increase ( λ ) in the controls (0.30 and 1.36 d −1 ) were significantly higher than in the LC 30 treatment (0.25 and 1.29 d −1 ); whereas, they were almost identical to values for the LC 10 treatment. No change in mean generation time ( T ) was observed at sublethal concentrations treatments. CONCLUSION Our results demonstrated that fluralaner has high acaricidal activity and could be considered a potential acaricide for TSSM management. © 2019 Society of Chemical Industry
研究领域:
农业科学
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害虫管理
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植物保护
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高影响因子
JOURNAL OF ASIA-PACIFIC ENTOMOLOGY
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2023
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IF 1.5
Shanshan Gao,Xinyi Zhang,Can Zhou,Guangyan Zhang,Yonglei Zhang,Ruimin Li,Kunpeng Zhang
Insect odorant binding proteins (OBPs) paly an important role in the recognition and transmission signals. One odorant binding protein gene, TcasOBP7G , was significantly up-regulated after exposure to eucalyptol. Nevertheless, the causal role of TcasOBP7G in Tribolium castaneum is still unclear. Here, TcasOBP7G was cloned and characterized from T. castaneum , aligning with the typical characteristic of Minus-C OBPs. The analysis of gene expression profile showed that TcasOBP7G is highly expressed at late larval and adult stage, with particularly high expression levels in ovary and testis of adults, suggesting that TcasOBP7G might be associated with reproduction of T. castaneum. Furthermore, RNAi of TcasOBP7G led to a decrease in spawning, while the development of gonads was normal, suggesting that TcasOBP7G may medicate the reproduction of T. castaneum . Additionally, the mRNA level of TcasOBP7G was significantly increased after exposure to eucalyptol, and knockdown of TcasOBP7G resulted in an increased susceptibility of T. castaneum to eucalyptol, indicating that TcasOBP7G is associated with the tolerance of T. castaneum to eucalyptol. Altogether, these results indicate that TcasOBP7G is required for both reproduction and defense against phytochemical in T. castaneum . This study will provide a theoretical basis for the development of novel control strategies based on the olfaction of insects.
研究领域:
昆虫学
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分子生物学
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昆虫生理学
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高影响因子
International Journal of Environmental Research and Public Health
·
2019
·Vol. 16
·期 2
·209
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IF 2.468
Huihui Chen,Xiaohong Gu,Qingfei Zeng,Zhigang Mao
As one of the most frequently detected pharmaceutical compounds in aquatic environments, carbamazepine (CBZ) has recently been shown to cause acute and chronic toxicity in a variety of non-target aquatic organisms. However, little is known about the ecotoxicological effects it has on the molting and reproduction of crustaceans. The aim of the present work was to evaluate the acute and chronic toxic responses to CBZ in the crustaceanDaphnia similis. After acute exposure (4 days), CBZ did not cause lethal toxicity at the tested concentrations. However, CBZ did inhibit the molting and release of chitobiase at concentrations higher than 6.25 μg/L, with 96 h EC50(median effective concentration) values of 864.38 and 306.17 μg/L, respectively. The results of chronic exposure showed that the mean number of molts, size of the first brood, mean number of offspring per brood, mean number of broods per female, and total offspring per female decreased significantly with increasing CBZ concentrations. Significant effects of CBZ on the molting or fecundity inD. similiswere observed even at concentrations as low as 0.03 μg/L. In conclusion, CBZ can cause inhibition of molting, delayed reproduction, and reduced fecundity inD. similis. CBZ toxicity toD. similisdepends on the timing and duration of the exposure. Moreover, our results indicated that CBZ would act as an endocrine disrupter inD. similis, as with vertebrates (e.g., fish).Keywords:carbamazepine;molting;Daphnia similis;chitobiase;chronic toxicity;reproduction
研究领域:
环境毒理学
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水生生态学
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医药污染
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PubMed
高影响因子
Insects
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2022
·Vol. 13
·期 8
·701
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IF 3.139
Xue Pan,Yanfang Pei,Cuici Zhang,Yaling Huang,Ling Chen,Liqiong Wei,Chuanren Li,Xiaolin Dong,Xiang Chen
Simple SummaryThe tobacco cutworm,Spodoptera litura(F.), exemplifies strong reproductive capacities and damages many agricultural crops. The insulin signaling pathway is known as a key determinant of female reproduction in insects. However, the detailed molecular mechanisms in these processes are poorly studied. Here, we injected bovine insulin into the newly emerged moth, resulting in gene expression changes in the insulin pathway, while knockdown ofSlInRcaused an inverse gene expression change involved in the insulin pathway. Further studies indicated that the content of JH-III, Vg, total proteins and triacylgycerol could be suppressed bySlInRdsRNA injection. Furthermore, stunted ovaries and lower fecundity were observed by RNAi. Our studies indicated that SlInR plays a key role in JH-III synthesis and the ovarian development inS. litura.AbstractInsulin signaling can regulate various physiological functions, such as energy metabolism and reproduction and so on, in many insects, including mosquito and locust. However, the molecular mechanism of this physiological process remains elusive. The tobacco cutworm,Spodoptera litura, is one of the most important pests of agricultural crops around the world. In this study, phosphoinositide 3-kinase (SlPI3K), protein kinase B (SlAKT), target of rapamycin (SlTOR), ribosomal protein S6 kinase (SlS6K) and transcription factor cAMP-response element binding protein (SlCREB) genes, except transcription factor forkhead box class O (SlFoxO), can be activated by bovine insulin injection. Then, we studied the influence of the insulin receptor gene (SlInR) on the reproduction ofS. liturausing RNA interference technology. qRT-PCR analysis revealed thatSlInRwas most abundant in the head. TheSlPI3K,SlAKT,SlTOR,SlS6KandSlCREBgenes were decreased, exceptSlFoxO,after theSlInRgene knockdown. Further studies revealed that the expression of vitellogenin mRNA and protein, Methoprene-tolerant gene (SlMet), could be down-regulated by the injection of dsRNA ofSlInRsignificantly. Furthermore, a depletion in the insulin receptor by RNAi significantly decreased the content of juvenile hormone III (JH-III), total proteins and triacylgycerol. These changes indicated that a lack ofSlInRcould impair ovarian development and decrease fecundity inS. litura. Our studies contribute to a comprehensive insight into reproduction, regulated by insulin and the juvenile hormone signaling pathway through nutrition, and a provide theoretical basis for the reproduction process in pest insects.Keywords:insulin pathway;juvenile hormone;reproduction;vitellogenin;nutrition
研究领域:
昆虫学
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分子生物学
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农业科学
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PubMed
高影响因子
AQUACULTURE NUTRITION
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2024
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IF 3
Xiaorong Huang,Ru Tan,Zhi Geng,Tao Zhang,Guangpeng Feng,Gang Yang,Feng Zhao,Ping Zhuang
A 60-day feeding trial was conducted to evaluate the impact of dietary Antarctic krill meal on the reproductive performance and embryo quality of the Chinese mitten crab, Eriocheir sinensis. Three diets were formulated, incorporating varying levels of Antarctic krill meal at 0% (Diet K0), 10% (Diet K10), and 20% (Diet K20), with a control group fed razor clam Sinonovacula constricta. Each diet was randomly assigned to three replicate tanks, each stocked with 5 males and 10 females. Male and female weights were 145.38 ± 8.01 and 102.57 ± 9.73 g, respectively. The results revealed no significant differences in weight gain rate, specific growth rate, and survival rate. However, the hepatopancreatic weight and hepatopancreas index of female crabs in each group decreased, while gonadal weight and gonadosomatic index increased significantly after 60 days, with Diet K20 showing the highest values. Egg production and fecundity of female crabs reached their peak in Diet K20, with no significant differences in reproductive indices among all groups. The phospholipid content in Diet K20 was significantly higher than in the other groups (). Cholesterol contents in Diet K0 and the control group were significantly higher than in Diet K10 and K20 (). No significant differences were observed in egg diameter, egg weight, moisture, crude protein, and crude fat between the groups. The content of C20 : 2 and C20 : 4n6 was highest in Diet K0, with a significant difference compared to Diet K10 (). However, no significant differences were found in the total content of saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids among all groups. Based on the research findings, it is recommended that the optimal level of Antarctic krill meal in diets is 20%.
研究领域:
水产养殖学
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动物营养学
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PubMed
高影响因子