JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2019
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IF 3.571
Yi Zhao,Mu-Zi Li,Yue Shen,Jia Lin,Hao-Ran Wang,Milton Talukder,Jin-Long Li
As a plasticizer, di(2-ethylhexyl) phthalate (DEHP) is the most usually used phthalate. Leydig cell is a male-specific cell, which plays a principal role in spermatogenesis and masculinization by the androgens of synthesis and secretion. Numerous researchers have indicated that DEHP can result in testicular toxicity by inducing oxidative stress. Lycopene (LYC) is a possible treatment option for male infertility due to its natural antioxidant properties. Our study was aimed to investigate whether LYC could rescue DEHP-induced Leydig cell damage. The mice were treated with DEHP (500 mg/kg BW/day or 1000 mg/kg BW/day) and/or LYC (5 mg/kg BW/day) for 28 days. We found that LYC attenuated DEHP-induced Leydig cell damage. Moreover, the protective role of LYC was verified by the histopathological and ultrastructural analysis of the Leydig cell. LYC suppressed oxidative stress that was induced by DEHP. In the Leydig cell, the expressions of the nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes were improved through LYC-mediated protection in DEHP-induced Leydig cell damage. Our findings indicated that LYC could increase the antioxidant capacity via mediating Nrf2 signaling pathway, thereby attenuating DEHP-induced Leydig cell damage.
研究领域:
毒理学
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生殖生物学
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药理学
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DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2024
·
IF 5.7
Lingjun Cheng,Yuanyuan Yang,Shaobin Lin,Canping Su,Mingming You,Yating Liu,Qingfei He,Jiaming Chen,Zhenyu Lin,Guolin Hong
Background Gold nanoclusters (AuNCs) obtained by electroreduction have excellent electrochemiluminescence (ECL) properties, and its ECL intensity is regulated by the valence state. In addition, their ECL signals can be rapidly quenched by reactive oxygen species (ROS). Based on this observation, a sensitive ROS biosensor was designed based on valence regulation of AuNCs. Excessive ROS in seminal plasma can lead to male infertility, and the short half-life and instability of ROS pose a challenge for their detection. Since valence regulation can be done quickly and is very sensitive, this ECL biosensor holds promise to address this issue. Results The ECL mechanism of AuNCs and the quenching mechanism of AuNCs by ROS were explored, mainly because ROS change the valence state of AuNCs. The ECL signals of the biosensor have a linear relationship with logarithm of the target concentration in the range of 1.0 × 10 −8 to 1.0 × 10 −3 M and 1.0 × 10 −3 to 1.0 × 10 −1 M, with a detection limit of 0.75 × 10 −10 M (S/N = 3). The biosensor enables rapid one-step detection of ROS and has the advantage of being stable and reusable. More notably, the results of 57 real samples showed that the biosensor can be used to accurately assess the concentration of seminal plasma ROS, guiding the monitoring of sperm quality and the diagnosis of male infertility. Significance Compared with the traditional strategy of applying AuNCs only as a luminescent body, this strategy of regulating the valence state of AuNCs to achieve sensitive and rapid detection broadens the application of AuNCs in the field of analysis. Compared with other ROS detection strategies, the one-step immediate detection method effectively avoids the inaccuracy caused by the short half-life and natural dissipation of ROS, and is expected to improve the accuracy and efficiency of clinical diagnosis.
研究领域:
分析化学
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生殖医学
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产品关联
DOI
PubMed
高影响因子
iScience
·
2024
·
IF 4.6
Ziqi Wang,Tongtong Li,Dongkai Liu,Mengjing Li,Shangming Liu,Xiaochen Yu,Hanzhen Li,Hui Song,Wei Zhao,Zhaojian Liu,Xiangfeng Chen,Gang Lu,Zi-Jiang Chen,Tao Huang,Hongbin Liu
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.
研究领域:
细胞生物学
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生殖医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Oncotarget
·
2017
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IF 5.168
Hao Gu,Wei Wu,Beilei Yuan,Qiuqin Tang,Dan Guo,Yiqiu Chen,Yankai Xia,Lingqing Hu,Daozhen Chen,Jiahao Sha,Xinru Wang
Genistein (GEN) is one of the isoflavones that has effect on male reproduction. However, the underlying mechanism remains unknown. miRNAs are a type of small non-coding RNAs that play important roles in spermatogenesis. We measured the GEN levels and miR-17-92 cluster expression in infertile subjects and found that miR-17-92 might be involved in GEN induced abnormal spermatogenesis. To clarify, we fed adult ICR mice with different doses of GEN (0, 0.5, 5, 50 and 250 mg/kg/day) for 35 days to study the underlying mechanism. We found that sperm average path velocity, straight-line velocity and eurvilinear velocity of the mice orally with GEN at 5mg/kg/day were significantly decreased, the expression levels of miR-17 and miR-20a in mice testis were higher in corresponding group. We also found miR-20a was the only miRNA that differentially expressed both in human and mice. By applying bioinformatics methods, Limk1 was predicted to be the target gene of miR-20a that is involved in spermatogenesis. Limk1 were significantly decreased in the corresponding group. Dual-luciferase report assay also proved that miR-20a could directly target Limk1. These results implied that Limk1 might be the target gene of miR-20a that is involved in GEN induced abnormal spermatogenesis.
研究领域:
生殖生物学
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分子生物学
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基因组学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Lingxiang Ran,Qiu Chen,Xingyu Lu,Zhixiang Gao,Fengmei Cui,Xiaolong Liu,Boxin Xue
Background Male infertility is a worldwide problem but few treatments, especially irradiation-induced testicular injury. The aim of this research was to investigate novel drugs for the treatment of irradiation-induced testicular injury. Methods We administered dibucaine (0.8 mg/kg) intraperitoneally to male mice (6 mice per group) after five consecutive daily 0.5 Gy whole-body irradiation, and evaluated its ameliorating efficacy by testicular HE staining and morphological measurements. Drug affinity responsive target stability assay (Darts) were used to find target protein and pathway; mouse primary Leydig cells were isolated and to explore the mechanism (Flow cytometry, Western blot, and Seahorse palmitate oxidative stress assays); finally rescue experiments were completed by combining dibucaine with fatty acid oxidative pathway inhibitors and activators. Results The testicular HE staining and morphological measurements in dibucaine treatment group was significantly better than that in irradiation group (P < 0.05); sperm motility and mRNA levels of spermatogenic cell markers were also higher than those in the latter (P < 0.05). Darts and Western blot results showed that dibucaine targets CPT1A and downregulate fatty acid oxidation. Flow cytometry, Western blot, and Palmitate oxidative stress assays of primary Leydig cells demonstrated that dibucaine inhibits fatty acid oxidation in Leydig cells. Dibucaine combined with etomoxir/baicalin confirmed that its inhibition of fatty acid oxidation was beneficial in ameliorating irradiation-induced testicular injury. Conclusions In conclusion, our data suggest that dibucaine ameliorates irradiation-induced testicular injury in mice by inhibiting fatty acid oxidation in Leydig cells. This will provide novel ideas for the treatment of irradiation-induced testicular injury.
研究领域:
药理学
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生殖生物学
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放射生物学
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产品关联
DOI
PubMed
高影响因子
PLANT PHYSIOLOGY
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2024
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IF 6.5
Liu Dandan,He Yuanrong,Wang Yijie,Chen Weiwei,Yang Jianli,Zhang Yuzhi,Feng Yaoyao,Zhao Yuxue,Lin Sue,Huang Li
Changing ambient temperature often impairs plant development and sexual reproduction, particularly pollen ontogenesis. However, mechanisms underlying cold stress-induced male sterility are not well understood. Here, we exposed Chinese cabbage (Brassica campestris) to different cold conditions during flowering and demonstrated that the tetrad stage was the most sensitive. After completion of pollen development at optimal conditions, transient cold stress at the tetrad stage still impacted auxin levels, starch and lipid accumulation, and pollen germination, ultimately resulting in partial male sterility. Transcriptome and metabolome analyses and histochemical staining indicated that the reduced pollen germination rate was due to the imbalance of energy metabolism during pollen maturation. The investigation of β-glucuronidase (GUS)-overexpressing transgenic plants driven by the promoter of DR5 (DR5::GUS report system) combined with cell tissue staining and metabolome analysis further validated that cold stress during the tetrad stage reduced auxin levels in mature pollen grains. Low-concentration auxin treatment on floral buds at the tetrad stage before cold exposure improved the cold tolerance of mature pollen grains. Artificially changing the content of endogenous auxin during pollen maturation by spraying chemical reagents and loss-of-function investigation of the auxin biosynthesis gene YUCCA6 by artificial microRNA technology showed that starch overaccumulation severely reduced the pollen germination rate. In summary, we revealed that transient cold stress at the tetrad stage of pollen development in Chinese cabbage causes auxin-mediated starch-related energy metabolism imbalance that contributes to the decline in pollen germination rate and ultimately seed set.
研究领域:
植物生理学
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分子生物学
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农学
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DOI
PubMed
高影响因子
Journal of Innovative Optical Health Sciences
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2024
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IF 2.3
Jiarui Wang,Shiyan Jiang,Jiaxin Shi,Jing Wang,Shengrong Du,Zufang Huang
Male infertility affects 10–15% of couples globally, with azoospermia — complete absence of sperm — accounting for 15% of cases. Traditional diagnostic methods for azoospermia are subjective and variable. This study presents a novel, noninvasive, and accurate diagnostic method using surface-enhanced Raman spectroscopy (SERS) combined with machine learning to analyze seminal plasma exosomes. Semen samples from healthy controls ( n = 3 2 ) and azoospermic patients ( n = 2 2 ) were collected, and their exosomal SERS spectra were obtained. Machine learning algorithms were employed to distinguish between the SERS profiles of healthy and azoospermic samples, achieving an impressive sensitivity of 99.61% and a specificity of 99.58%, thereby highlighting significant spectral differences. This integrated SERS and machine learning approach offers a sensitive, label-free, and objective diagnostic tool for early detection and monitoring of azoospermia, potentially enhancing clinical outcomes and patient management.
研究领域:
生殖医学
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生物医学工程
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分析化学
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医疗健康中的机器学习
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DOI
高影响因子
Biomedicines
·
2024
·Vol. 12
·期 8
·1632
·
IF 3.9
Hang Zhang,Nannan Li,Yukun Zhang,Yue Xu,Feng Lu,Dongmei Lin,Shuqian Lin,Min Li,Baoxue Yang
Chemotherapy is an important factor leading to male infertility. It is crucial to discover safe and effective treatments to prevent male reproductive injury caused by chemotherapy. TheGanoderma lucidumpolysaccharide peptide (GLPP) has multiple pharmacological activities. The purpose of this study was to determine whether GLPP could protect the male sperm production from chemotherapeutic injury using a mouse model, with testicular damage induced by cyclophosphamide (CP). CP (50 mg/kg/day) was injected intraperitoneally into male ICR mice gavaged with different doses of GLPP at certain spermatogenic stages. The experimental results showed that GLPP alleviated the CP-induced reduction in reproductive organ coefficients and sperm parameters and reduced the morphological damage of testicular tissues in a dose-dependent manner. GLPP significantly improved the reproductive index, sperm-related parameters, sex hormone levels, and histological testis architecture at different spermatogenic stages. Furthermore, GLPP significantly increased superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), Nrf2, and HO-1, and decreased malondialdehyde (MDA) and Keap-1 in the testicular tissue, indicating reduced oxidative stress. In addition, GLPP limited CP-induced apoptosis via a reduction in Bax expression and increase in Bcl-2 expression. This study suggests that GLPP plays a protective role in spermatogenesis by reducing chemotherapeutic injury and might be developed into drug for male patients receiving chemotherapy.
研究领域:
药理学
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生殖生物学
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肿瘤学
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DOI
PubMed
高影响因子
MOLECULAR THERAPY
·
2025
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IF 12
Mengya Zhang,Xueguang Zhang,Chen Tan,Ting Jiang,Zheng Cao,Yufei Chen,Feng Qiao,Gelin Huang,Chaoye Ma,Huixia Li,Mei Ye,Lei Wang,Liandong Zuo,Jun Yu,Xiaofeng Li,Yunfang Zhang,Yue-Qiu Tan,Shuibin Lin,Wenming Xu,Hao Chen
Recent studies have highlighted RNA modifications as integral regulators of gene expression during spermatogenesis. Ribosomal RNAs (rRNAs) are the most abundant RNA in cells, while the function and clinical relevance of rRNA modifications in spermatogenesis remain poorly understood. Here, we identified 4 pathogenic heterozygous variants of METTL5 in 1,427 patients with male infertility characterized as oligoasthenoteratozoospermia (OAT). The pathogenic variants of METTL5 led to the significantly decreased expression level of METTL5. Null mutation of 18S rRNA methyltransferase Mettl5 led to male infertility attributed to OAT during spermiogenesis, presenting defects in both the sperm head and tail. Notwithstanding the absence of notable changes in global translation after Mettl5 loss, we observed a compromised translational efficiency of mRNAs encoding proteins crucial for spermiogenesis, including Gk2 , Akap4 , Fsip2 , Odf2 , and Pgk2 . Intriguingly, therapeutic interventions via intracytoplasmic sperm injection in OAT couples with these variants resulted in successful pregnancies. These insights not only identify METTL5-mediated 18S rRNA m 6 A modification as a novel genetic determinant for OAT but also offer a new target to the genetic counseling, clinical diagnosis, and potential treatment strategies for male infertility.
研究领域:
分子生物学
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遗传学
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生殖医学
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RNA修饰
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发育生物学
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产品关联
DOI
PubMed
高影响因子
AQUACULTURE
·
2022
·
IF 5.135
Jing Wang,Wen Wang,Jihong Li,Ziye Luo,Zhanxin Li,Mingli Chai,Caixia Xiang,Kaikun Luo,Rurong Zhao,Shaojun Liu
Sex hormones play an important role in gametogenesis . During the breeding season, sex hormone levels in the sterile allotriploid crucian carp (3nAT) were significantly lower than those in the fertile diploid red crucian carp (2nRCC). Sex hormone rescue was performed to study the relationship between sex hormones and 3nAT sterility. For three months before breeding season, 3nAT females and males were fed the sex hormones estradiol and testosterone, respectively. During breeding season, hormone-rescued 3nAT fish (re-3nAT) showed normal reproductive behavior, and levels of estradiol in female re-3nAT and testosterone in male re-3nAT were similar to those of the diploid control (2nRCC). The vtg gene, which is associated with the hepatic synthesis of vitellogenin in the female, and the genes spef2, tekt1, and ift27 , which are associated with the formation of the sperm flagellum, were significantly upregulated in re-3nAT as compared to 3nAT. Under artificially assisted reproduction, re-3nAT individuals produced a few eggs of different sizes and sperm with abnormal structures. However, few individuals had insemination ability. Neither zygotes produced by self-crossing re-3nAT nor those produced by crossing re-3nAT with the haploid gametes produced by 2nRCC exhibited normal embryonic development. Thus, although sex hormone treatment led to the production of abnormal gametes by re-3nAT, viable offspring did not develop, meaning that re-3nAT remained sterile. These results indicated that sex hormones affected gamete maturation but were not the determinant of triploid sterility.
研究领域:
生物学
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生殖生物学
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遗传学
✓ 已验证
DOI
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2022
·
IF 14.224
Yi Zhao,Xue-Nan Li,Hao Zhang,Jia-Gen Cui,Jia-Xin Wang,Ming-Shan Chen,Jin-Long Li
Male infertility is an attracting growing concern owing to decline in sperm quality of men worldwide. Phthalates , in particular to di (2-ethylhexyl) phthalate (DEHP) or its main metabolite mono-2-ethylhexyl phthalate (MEHP), affect male reproductive development and function, which mainly accounts for reduction in male fertility. Lycopene (LYC) is a natural antioxidant agent that has been recognized as a possible therapeutic option for treating male infertility. Testosterone (T)/androgen receptor (AR) signaling pathway is involved in maintaining spermatogenesis and male fertility. How DEHP causes spermatogenesis disturbance and whether LYC could prevent DEHP-induced male reproductive toxicity have remained unclear. Using in vivo and vitro approaches, we demonstrated that DEHP caused T biosynthesis reduction in Leydig cell and secretory function disorder in Sertoli cell, and thereby resulted in spermatogenic impairment. Results also showed that MEHP caused mitochondrial damage and oxidative damage, which imposes a serious threat to the progress of spermatogenesis. However, LYC supplement reversed these changes. Mechanistically, DEHP contributed to male infertility via perturbing T/AR signaling pathway during spermatogenesis. Overall, our study reveals critical role for T/AR signal transduction in male fertility and provides promising insights into the protective role of LYC in phthalate-induced male reproductive disorders.
研究领域:
生殖生物学
·
毒理学
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内分泌学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
HUMAN REPRODUCTION
·
2022
·Vol. 37
·期 7
·1394-1405
·
IF 6.353
Liu Ruyi,Yan Zheng,Fan Yong,Qu Ronggui,Chen Biaobang,Li Bin,Wu Ling,Wu Haibo,Mu Jian,Zhao Lin,Wang Wenjing,Dong Jie,Zeng Yang,Li Qiaoli,Wang Lei,Sang Qing,Zhang Zhihua,Kuang Yanping
STUDY QUESTIONAre there new genetic factors responsible for male infertility with normal sperm quantity and morphology?SUMMARY ANSWERWe identified the bi-allelic variants in KCNU1 and confirmed it a novel pathogenetic gene for male infertility mainly due to impaired sperm acrosome reactions (ARs).WHAT IS KNOWN ALREADYUntil now, the underlying genetic determinants for male affected individuals exhibiting normal sperm quantity and morphology have been largely unknown. Potassium/calcium-activated channel subfamily U member 1 (KCNU1) is a sperm-specific potassium channel. The Kcnu1 null mutation in male mice causes infertility due to the impaired progressive motility and AR.STUDY DESIGN, SIZE, DURATIONWe recruited a cohort of 126 male infertility individuals with typical asthenospermia or fertilization failure and focused on two infertile males from two consanguineous families from 2015 to 2020; whole-exome sequencing and homozygosity mapping were performed. We identified a homozygous missense variant (c.2144A>G, p.His715Arg) and a homozygous donor splice-site variant (c.1295 + 3A>C, p.Val405Glyfs*8) in KCNU1. Then, we generated a knock-in (KI) mouse model in September 2020 and have now carried out functional studies and possible treatment strategies.PARTICIPANTS/MATERIALS, SETTING, METHODSThe affected individuals with infertility were recruited from the Shanghai Ninth Hospital affiliated to Shanghai Jiao Tong University. Genomic DNA from the affected individual was extracted from peripheral blood. Whole-exome sequencing, homozygosity mapping and in silico analyses were used to screen and identify KCNU1 variants, and the variants were confirmed by Sanger sequencing. We used C57BL/6N mouse to construct KI mouse model to mimic the reproductive phenotype in vivo. We performed functional experiments by western blotting, AR assay and immunofluorescent Staining. Finally, we performed IVF and ICSI to explore the treatment strategies.MAIN RESULTS AND THE ROLE OF CHANCEWe identified a homozygous missense variant (c.2144A>G, p.His715Arg) and a homozygous donor splice-site variant (c.1295 + 3A>C, p.Val405Glyfs*8) in KCNU1 in two infertile males. We demonstrated that the splice-site variant affected normal alternative splicing of KCNU1, thus leading to the loss of function of KCNU1. Meanwhile, the missense pathogenic variant reduced the KCNU1 protein levels in sperm of both the affected individual and the KI mouse model, resulting in impaired ARs and male infertility. Intracytoplasmic sperm injection was able to rescue the deficiencies.LARGE SCALE DATAN/A LIMITATIONS, REASONS FOR CAUTIONThe exact molecular mechanism of KCNU1 and pathways need to be further explore in the future.WIDER IMPLICATIONS OF THE FINDINGSThis is the first report that establishes a causal relationship between KCNU1 deficiency and male infertility, confirming the critical role of KCNU1 in human reproduction. Our findings expand our knowledge of the genes that play critical roles in the human sperm AR and provide a new genetic marker for infertility.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by the SHIPM-pi fund no. JY201801 from the Shanghai Institute of Precision Medicine, Ninth People’s Hospital Shanghai Jiao Tong University School of Medicine, the National Natural Science Foundation of China (81725006, 81771649, 81822019, 81771581, 81971450, 81971382, 82001538 and 82071642). The authors declare no conflict of interest.TRIAL REGISTRATION NUMBERN/A.
研究领域:
遗传学
·
生殖生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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