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Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

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Neural Regeneration Research 2025年第1期20卷 265-276页

作者： Yao Yuan Lingqi Yu Xudong Zhuang Dongjing Wen Jin He Jingmei Hong Jiayu Xie Shengan Ling Xiaoyue Du Wenfeng Chen Xinrui Wang Institute of Life Sciences College of Biological Science and EngineeringFuzhou UniversityFuzhouFujian ProvinceChina NHC Key Laboratory of Technical Evaluation of fertility Regulation for Non-human Primate(Fujian Maternity and Child Health Hospital) FuzhouFujian ProvinceChina Medical Research center Fujian Maternity and Child Health HospitalCollege of Clinical Medicine for Obstetrics&Gynecology and PediatricsFujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology and Institute of Neurology of The First Affiliated Hospital Institute of Neuroscienceand Fujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian ProvinceChina

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory *** develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause *** located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)*** addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive *** these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut *** found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in *** heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal *** Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

关键词： ATP1A1 Atpα bang-sensitive paralysis Charcot-Marie-Tooth disease type 2 CRISPR/Cas9 homology-directed repair Na^(+)/K^(+)-ATPase point mutation seizures sodium pump

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Systematical identification of regulatory GPCRs by single-cell trajectory inference reveals the role of ADGRD1 and GPR39 in adipogenesis

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Science China Life Sciences 2025年

作者： Chuan Ye Xuemei Wang Jun Lin Chenyang Wu Yuhua Gao Chenghao Guo Yunxi Liao Ziyan Rao Shaodong Huang Weixuan Chen Ying Huang Jinpeng Sun Dongyu Zhao Changtao Jiang center of Basic Medical Research Institute of Medical Innovation and ResearchPeking University Third Hospital Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking University Department of Biomedical Informatics School of Basic Medical SciencesPeking University State Key Laboratory of Vascular Homeostasis and Remodeling Peking University center for Obesity and Metabolic Disease Research School of Basic Medical SciencesPeking University State Key Laboratory of Female fertility Promotion Center for Reproductive MedicineDepartment of Obstetrics and GynecologyPeking University Third Hospital National Clinical Research center for Obstetrics and Gynecology Peking University Third Hospital Department of Endocrinology and Metabolism Peking University Third Hospital Key Laboratory Experimental Teratology of the Ministry of Education Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesCheeloo College of MedicineShandong University Department of Immunology School of Basic Medical SciencesPeking University

Adipogenesis is the healthy expansion of white adipose tissue (WAT),serving as a compensatory response to maintain metabolic homeostasis in the presence of excess energy in the ***,the identification of novel regulatory molecules in adipogenesis,specifically membrane receptors such as G protein-coupled receptors (GPCRs),holds significant clinical *** receptors can serve as viable targets for pharmaceuticals,offering potential for restoring metabolic homeostasis in individuals with *** utilized trajectory inference methods to analyze three distinct single-nucleus sequencing (sNuc-seq) datasets of adipose tissue and systematically identified GPCRs with the potential to regulate *** verification in primary adipose progenitor cells (APCs) of mice,we discovered that ADGRD1 promoted the differentiation of APCs,while GPR39 inhibits this *** the obese mouse model induced by a high-fat diet(HFD),both gain-of-function and loss-of-function studies validated that ADGRD1 promoted adipogenesis,thereby improving metabolic homeostasis,while GPR39 inhibited adipogenesis,leading to metabolic ***,through the analysis of 2,400 ChIP-seq data and 1,204 bulk RNA-seq data,we found that the transcription factors (TFs) MEF2D and TCF12 regulated the expression of ADGRD1and GPR39,*** study revealed the regulatory role of GPCRs in adipogenesis,providing novel targets for clinical intervention of metabolic dysfunction in obese patients.

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Pyospermia in Men Seeking Assisted Reproduction Technology

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Open Journal of Urology 2018年第4期8卷 93-107页

作者： Abayomi B. Ajayi Bamgboye M. Afolabi Victor D. Ajayi Ifeoluwa O. Oyetunji Oluwafunmilola R. Biobaku Adedamilola Atiba Joy Ehichioya Ibukun Ayelehin Ayodeji Adeoye Temilade Adesida nordica fertility center Lagos Nigeria Health Environment and Development Foundation Lagos Nigeria

Introduction: Pyospermia is often detected in semen, especially when investigating for male infertility. Pyospermia, in a significantly large number is often correlated with inferior sperm parameters and reduced fertility. Pyospermia may be a factor of a fundamental genitourinary infection. This study assessed the relationship between pus cells and semen parameters in infertile Nigerian males. Subjects and Methods: A cross-sectional descriptive study was carried out at nordica fertility center, Lagos, Nigeria, from 2004 to 2009. A total of 907 subjects were analyzed. Subjects ages (years) were categorized into ≤30, 30.1 - 35, 35.1 - 40, 40.1 - 45, 45.1 - 50 and >50, BMI into Results: Leucocytopenia of ≥3 per high power field (/hpf) occurred in 67 (7.4%) men. The overall means (±sd) of pus cells was 1.4 (0.9), 1.4 (0.7), 1.4 (0.7) and 1.6 (1.6) per high power field in all, normospermia, oligoospermic and azoospermic clusters of patients respectively. Mean (±sd) pus cells in semen was 6.0 (4.0), the highest, among obese (BMI ≥ 30) azoospermic patients. The proportion of subjects with pyospermia of 1 - 2 was highest (323/346, 93.3%) among oligoospermic patients while that with pyospermia of ≥3 was highest (10/109, 9.2%) among azoospermic patients. Obese azoospermic patients were 1.8 times as likely to have ≥3/hpf pyospermia compared to normal normospermic patients (x2 = 0.05, P-value = 0.51, OR = 1.82, 95% CI: 0.30, 11.02). Mean progressive motility (%) was significantly reduced (t = 1.95, P-value = 0.03) among patients with ≥3/hpf pyospermia (33.75 ± 19.23) compared to those with 1 - 2/hpf pyospermia (38.58 ± 21.63). Patients with sperm oval head ≤ 30% had significantly higher pyospermia (t = 2.22, P-value = 0.013) than those with sperm oval head of >30%. Conclusion: Elevated pus cell counts were observed among obese azoospermic men, those with reduced sperm progressive motility and those with lower count of sperms with oval head morphology. Clinicians should consider

关键词： Pyospermia Male Infertility Progressive Motility Oval Head Nigeria

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Frequency of Monthly Ejaculation at Sexual Intercourse, DNA Fragmentation Index and Fertilization Rate among Sperm Donors and fertility-Challenged Men in Sub-Saharan Africa: Paper 2

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Open Journal of Urology 2020年第3期10卷 60-78页

作者： Abayomi B. Ajayi Bamgboye M. Afolabi Victor D. Ajayi Ifeoluwa O. Oyetunji Adedamilola Atiba Seun Saanu Ayodeji T. Adeoye Joy I. Ehichioya Ibukun I. Ayelehin nordica fertility center Lagos Nigeria Health Environment and Development Foundation Lagos Nigeria

Introduction: Heterogenous sexual intercourse often produces a powerful orgasm that stimulates the pituitary function. Studies have suggested ejaculation frequency based on age. Materials and Methods: Semi-structured questionnaires were used to collect information from subjects. Semen samples were collected from sperm donors and sub-fertile men who presented for infertility challenges. Processing and analysis of semen samples were done according to World Health Organization (WHO) guidelines. Sperm deoxyribonucleic acid (DNA) fragmentation was evaluated using the Halosperm kit. Results: Among sperm donors, those aged χ2 = 0.09, P-value = 0.81, OR = 3.2, 95% CI: 0.23, 45.19) while among sub-fertile men those aged ≥40 years were approximately 2.3 times more likely to have very low frequency of MESI compared to aged χ2 = 2.11, P-value = 0.51, OR = 2.27, 95% CI: 0.74, 9.92). The frequency of all categories of MESI was highest among sub-fertile men aged χ2 = 0.03, P-value = 0.57, OR = 2.42, 95% CI: 0.41, 14.46). Sub-fertile men aged ≥40 with diastolic hypertension (≥90 mmHg) were approximately 6 times more likely to have a low (6 - 10) frequency of MESI compared to those aged χ2 = 1.97, P-value = 0.16, OR = 6.22, 95% CI: 0.69, 55.77). Overall mean fertilization rate was significantly higher (t-test = 2.44, P-value = 0.01) among sub-fertile men aged Conclusion: Cigarette smoking, more than alcohol consumption, appears to be a major factor that significantly affects the frequency of MESI among sub-fertile men in all age groups. Frequency of MESI negatively but insignificantly correlated with systolic blood pressure.

关键词： Monthly Ejaculation at Sexual Intercourse Systolic and Diastolic Blood Pressures DNA Fragmentation Index Fertilization Rates Social Habits Sub-Fertile Males Sub-Sahara Black Africans

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Evaluation of Sperm DNA Fragmentation amongst Infertile Black Africans. A Nigerian Study

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Open Journal of Urology 2018年第11期8卷 297-316页

作者： Abayomi B. Ajayi Bamgboye M. Afolabi Victor D. Ajayi Ifeoluwa O. Oyetunji Adedamilola Atiba Seun Saanu Ayodeji T. Adeoye Temilade E. Adeshida Joy Ehichioya Ibukun I. Ayelehin nordica fertility center Lagos Nigeria Health Environment and Development Foundation Lagos Nigeria

Background: Male infertility is approaching an epidemic proportion. Almost 50% of all cases of infertility may be associated with a male factor. The diagnostic usefulness of sperm DNA integrity is now accessible as an additional tool to Seminal Fluid Analysis. Objective: To assess sperm DNA fragmentation index (SDFI) in male infertility and its relationship with obesity, alcohol consumption and cigarette smoking among infertile Nigerians. Patients and Methods: Patients who presented for infertility at three health facilities of nordica fertility center in Lagos, Asaba and Abuja cities in Nigeria. STATA 13 was used for student’s t-test to compare the means of continuous variables among smokers and non-smokers and among alcohol consumers and non-consumers. Linear regression analysis was employed to assess the correlation between SDFI as dependent variable and some independent variables. Results: There was no significant difference in the SDFI of men aged −1.80, P-value = 0.04) than that of obese men (30.2%). Obese men were 2.12 times as likely to have SDFI ≥25% compared to normal weight men (χ2-2.16, P-value = 0.14, OR = 2.12, 95% CI: 0.77, 5.80). Mean SDFI of men who consume alcohol (37.1%) was significantly higher (t = −1.97, P-value = 0.03) than that of those who did not consume alcohol. Although Pearson’s correlation matrix (r) indicated that sperm DNA fragmentation index was positively correlated with history of infertility (r = 0.01), groin surgery (r = 0.04), mumps (r = 0.04) and sexually transmitted illness (r = 0.04), however the degree of correlation was not significant (P-value ≥ 0.5) in each case. Conclusion: This is the first report in Black Africa that describes a correlation between sperm DNA integrity, as measured by the halo test and age, BMI and alcohol consumption. Men with normal BMI were more likely to have excellent to good SDFI and hence good fertility potential. Data from this study indicate that the infertile men had significan

关键词： Sperm Fragmentation Index Obesity Alcohol Consumption Male Infertility Assisted Reproduction Technology Black Africans

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Frequency of Monthly Ejaculation at Sexual Intercourse, DNA Fragmentation Index and Fertilization Rate among Sperm Donors and fertility-Challenged Men in Sub-Saharan Africa: Paper 1

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Open Journal of Urology 2019年第11期9卷 181-194页

作者： Abayomi B. Ajayi Bamgboye M. Afolabi Victor D. Ajayi Ifeoluwa O. Oyetunji Adedamilola Atiba Seun Saanu Ayodeji T. Adeoye Joy Ehichioya Ibukun I. Ayelehin nordica fertility center Lagos Nigeria Health Environment and Development Foundation Lagos Nigeria

Introduction: In humans, the ideal ejaculation frequency depends on age, exercise and sexual potential. Natural ejaculation frequency balances the testosterone levels in the body. Materials and Methods: Semi-structured questionnaire was used to collect information from subjects. Semen samples were collected from sperm donors and sub-fertile men who presented for infertility challenges. Processing and analysis of semen samples were done according to World Health Organization guidelines. Sperm DNA fragmentation was evaluated using the Halosperm®?kit. Results: A total of 114 subjects, including 19 sperm donors and 95 sub-fertile males were studied. There was a significant difference (t =?−5.96, P-value = 0.00001) in the mean [±sd] age of sperm donors (30.8 [8.1]) and that of sub-fertile men (42.3 [76]). There was a significant difference (t=?−4.10, P-value = 0.0005) in the mean monthly ejaculation during sexual intercourse (MESI) among sperm donors with DNA fragmentation index −2.20, P-value = 0.02) in MESI among sub-fertile men aged ≥40 years (8.9 [4.6]) than among those aged −0.67, SE = 0.28, t = −2.40, P-value = 0.02, 95% CI: −1.24,?−0.10). Conclusion: In men < 40 years, fewer MESI did not worsen the DFI. A higher number of professionals such as doctors, lawyers and engineers, reported lower monthly frequency of sexual ejaculations compared to entrepreneurs. Entrepreneurs and non-smokers had the highest frequencies of MESI.

关键词： Monthly Sexual Ejaculation Rate DNA Fragmentation Index Male Infertility Age Group Body Mass Index Social Habits Black Africans

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Low Sperm Counts: Biophysical Profiles of Oligospermic Males in Sub-Saharan Africa

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Open Journal of Urology 2018年第8期8卷 228-247页

作者： Abayomi B. Ajayi Bamgboye M. Afolabi Victor D. Ajayi Ifeoluwa Oyetunji nordica fertility Centre Lagos Nigeria Health Environment and Development Foundation Lagos Nigeria

Introduction: Male infertility is a public health burden and a psychological dilemma in the life of the affected man. Subjects and Methods: A total of 911 men were studied retrospectively, from 2010 to 2015. Among these, 49.7% had normal sperm count, 39.3% were oligospermic and 12.0% were azoosper-mic. Azoospermic men were withdrawn from this study solely to investigate the seminal fluid parameters and the biophysical characteristics of oligospermic men in contrast to those with normal sperm count. Age was stratified into <30, 30 - 39.9, 40 - 49.9, 50 - 59.9 and ≥60 years;body mass index was categorized into underweight (<18.5), normal (18.5 - 24.9), overweight (25.0 - 29.9) and obese (≥30) and standard semen analysis was performed. Results: The means (±sd) of age and of BMI of the 802 subjects of the study were 42.7 (±7.0) years and 26.9 (3.9) kg/m2 respectively. There was no significant difference in the age or BMI of normal and oligospermic men. A total of 453 (56.5%) had normal sperm count while 349 (43.5%) were oligospermic. Compared to normal weight men, those overweight and those obese were, respectively, 1.11 (χ2 = 0.44, P-value = 0.51, OR = 1.11, 95% CI = 0.81, 1.54) and 1.56 times (χ2 = 4.50, P-value = 0.03, OR = 1.56, 95% CI = 1.03, 2.36) more likely to be oligo-spermic. The mean of normal oval head sperms was significantly higher (t = -7.31, P-value = 0.00001) in normal men (47.8 ± 8.9) than in oligospermic men (43.0 ± 10.7). Oligospermic men were over 4 times as likely to produce progressive sperm motility of <32% (χ2 = 70.90, P-value = 0.000001, OR = 4.24, 95% CI = 2.99, 6.02) than men with normal sperm count. Multivariate regression analysis shows negative but significant correlations between age and semen volume (coef. = - 0.04, Std Err. = 0.01, t = - 4.01, P-value = 0.0001, 95% CI: - 0.06, - 0.02) and between BMI and sperm count (coef. = - 0.18, Std Err. = 0.06, t = - 3.26, P-value = 0.001, 95% CI: - 0.29, - 0.07). Conclusion: Our findings suggest t

关键词： Oligospermia Age Body Mass Index Male Infertility Sperm Cell Defects

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Testicular sperm extraction(TESE)outcomes in the context of malignant disease:a systematic review

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Asian Journal of Andrology 2022年第6期24卷 584-590页

作者： Ludmilla Ogouma Isabelle Berthaut Rachel Lévy Rahaf Haj Hamid Marie Prades Marie Audouin Nathalie Sermondade Charlotte Dupont fertility center(Service de Biologie de la Reproduction CECOS) Tenon Hospital(AP-HPSorbonne-Universite)Paris F-75020France Sorbonne University Saint Antoine Research CenterInserm Us938Paris F-75012France fertility center Diaconesses HospitalParis F-75012France

Advances in the oncology field have led to improved survival ***,quality of life after remission is anticipated,which includes the possibility to conceive *** cancer treatments are potentially gonadotoxic,fertility preservation must be *** fertility preservation is mainly based on ejaculated sperm *** this is not possible,testicular sperm extraction(TESE)may be *** identify situations in which TESE has been beneficial,a systematic review was *** search was carried out on the PubMed,Scopus,Google Scholar,and CISMeF databases from 1 January 2000 to 19 March *** Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)recommendations were followed in selecting items of ***-four articles were included in the systematic review,including 15 articles on oncological testicular sperm extraction(oncoTESE),18 articles on postgonadotoxic treatment TESE and 1 article on both oncoTESE and postgonadotoxic treatment *** sperm freezing was possible for 42.9%to 57.7%of patients before gonadotoxic treatment and for 32.4%to 75.5%of patients after gonadotoxic treatment,depending on the type of malignant *** no formal conclusion could be drawn about the chances to obtain sperm in specific situations,our results suggest that TESE can be proposed before and after gonadotoxic *** treatment,TESE is more often proposed for men with testicular cancer presenting with azoospermia since TESE can be performed simultaneously with tumor removal or *** chemotherapy,TESE may be planned if the patient presents with persistent azoospermia.

关键词： cancer fertility preservation oncological testicular sperm extraction spermatozoa testicular sperm extraction

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Men without Sperms

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Open Journal of Urology 2018年第1期8卷 25-42页

作者： Abayomi B. Ajayi Bamgboye M. Afolabi Victor D. Ajayi Ifeoluwa Oyetunji Oluwafunmilola Biobaku Adedamilola Atiba nordica fertility Centre Lagos Nigeria Health Environment and Development Foundation Lagos Nigeria

Introduction: Men without sperm (azoospermic) make up about 15% of all infertile men in reproductive age of fatherhood. Male infertility is a health and social problem in many communities. Subjects and Methods: This retrospective study was carried from 2010 to 2015. Initially, 907 men were included in the study among whom 109 (12.02%), 346 (38.15%) and 452 (49.83%) were azoospermic, oligospermic and normospermic, respectively. This study only investigated the association between age, BMI, semen volume, liquefaction time and pus cells among normospermic and azoospermic men. Standard semen analysis was performed and subjects were categorized by age into Results: The 562 subjects of the study had means (±sd) age of 42.6 (±7.10) years and BMI of 27.0 (4.1) kg/m2 respectively. In all, 109 (19.4%) were azoospermic. Overweight and obese men were, respectively, more than 1? and about 2? times more likely to be azoospermic compared to normal weight men. Azoospermic men were significantly heavier than men with normal sperm count (t = -0.34;P-value = 0.003). Among those with normal weight, liquefaction time was significantly shorter (t = 5.49, P-value = 0.000001) in azoospermic (28.70 min.) than in men with normal sperm count (31.82 min.). Obese azoospermic men were about 4 times as likely to have high pus cells in semen than normal weight azoospermic men (OR = 3.82;95% CI: 0.39, 37.01). Multivariate regression analysis shows a strong but negative coefficient correlation between sperm concentration and BMI (coef. = -0.48, Std Err. = 0.25, P-value = 0.05, 95% CI: -0.96, 0.10). Conclusion: Our findings suggest that high BMI is associated with azoospermia. Azoospermia also did not seem to negatively impact liquefaction time.

关键词： Azoospermia Normal Sperm Concentration Age Body Mass Index Male Infertility Sub-Sahara Africa

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The effects of 2-Bromopropane on Viability and TestosteroneProduction Ability of Rat Leydig Cells in Primary Culture

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Biomedical and Environmental Sciences 1999年第1期12卷 43-49页

作者： YANG JIAN-MING WU XIAO-YUN DING XUN-CHENG PANG BING JIANG XUE-ZHI (National Evaluation center for the Toxicology of Fertilicy Regulating Drugs,Shanghai 200032, China) JI ZAI-SI AND SHIN KAZUO( MeiJi Institute of Health Science,Odewara 250, Japan)WU National Evaluation center for the Toxicology of fertility Regulating Drugs Shanghai China. xidowu@***

Epidemiological surveys and animal experiments have shown that 2-bromopropane induces oligozoospermia in exposed workers and inhibits spermatogensis in laborratory animals. However, themechanism by which 2-bromopropane exerts its effects is unknown. To this end, we examined the formation of testosterone by the Leydig cells and their survival of these cells in the Presence of differ-ent concentrations of 2-bromopropane in vitro. Leydig cells were isolated following vascular Perfu-sion, enzymatic dissociation and Percoll gradient centrifugation techniques. The cells were cultured in culture dishes. After 8 h, different cultures were exposed to 2-bromopropane at concentrations of 0.01 mmol/L, 0.10 mmol/L and 1.00 mmol/L. In order to stimulate Leydig cells to secrete testos-terone, human chorionic gonadotropin (hCG) was also added. Cell viability was determined using the trypan blue dye exclusion test and cell numbers were counted by hemocytometer. Testosterone secretion was detected by radioimmunoassay. The cell viability decreased after exposure to 2-bromo-propane in a dose-dependent way, but no morphological change was observed. The cell number de-creased in the 2-bromopropane-treated cultures. The secretion of testosterone did not manifest de -tectable changes in the culture treated with 0.10 mmol/L and 0.01 mmol/L of 2-bromopropane;however, it decreased significantly (P < 0. 02) in the Presence of 1.00 mmol/L. Therefore, ourresults strongly suggest that 2-bromopropane may exert its cytotoxic effects on heydig cells in *** speculate that the decrease in the numbers of Leydig cells caused by 2-bromopropane was medi-ated by a feedback mechanism resulting from a lower testosterone concentration.

关键词： Animals Cell Survival Cells, Cultured Hydrocarbons, Brominated Leydig Cells Male Rats Rats, Sprague-Dawley Spermatogenesis Testosterone

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