Yung‐Ming Lin

National Cheng Kung University Hospital

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Peter C. K. Leung

University of British Columbia

Hsun‐Ming Chang

China Medical University Hospital

Tsung‐Yen Lin

National Cheng Kung University Hospital

Yuyin Yi

British Columbia Children's Hospital

Chien‐Hui Ou

National Cheng Kung University

Chun-Wun Lu

Kaohsiung Chang Gung Memorial Hospital

Wen‐Horng Yang

Anhui Agricultural University

Yu‐Sheng Cheng

National Cheng Kung University Hospital

Hong‐Lin Cheng

Chongqing Medical University

Yat‐Ching Tong

National Cheng Kung University Hospital

Cooperative Institutions

National Cheng Kung University

National Cheng Kung University Hospital

University of British Columbia

British Columbia Children's Hospital

Tainan University of Technology

National University of Tainan

Kaohsiung Medical University

Chang Gung University

Kaohsiung Chang Gung Memorial Hospital

Chia Nan University of Pharmacy and Science

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TGF-β1 inhibits microvascular-like formation by decreasing VCAM1 and ICAM1 via the upregulation of SNAIL in human granulosa cells

Molecular and Cellular Endocrinology (2021)

Hui Li Hsun‐Ming Chang Yung‐Ming Lin Zhendan Shi Peter C. K. Leung

Matrigel

Granulosa cell

10.1016/j.mce.2021.111395

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Citations (9)

The MAEL expression in mitochondria of human spermatozoa and the association with asthenozoospermia

Andrology (2023)

Yu‐Sheng Cheng Hsing‐Yi Chen Yu‐Chiao Lin Yi‐Syuan Lin Yi‐Chun Yeh

The maelstrom spermatogenic transposon silencer (MAEL) function in postmeiotic germ cells remains unclear, and its protein localization in human testis and spermatozoa awaits determination. This study aims to clarify the MAEL expression in human spermatogenesis and to explore its role in sperm function.Twenty-seven asthenozoospermic men, 40 normozoospermic controls, and three obstructive azoospermic men were enrolled. The transcripts of MAEL in the seminiferous epithelium and MAEL downstream targets were identified by bioinformatics analysis. MAEL protein expression in human testis and ejaculated sperms were examined by immunohistochemical and immunogold staining, respectively. The roles of MAEL in mitochondria function were investigated by siRNA knockdown in human H358 cells. The association between MAEL protein levels and clinical sperm features was evaluated.Abundant MAEL was expressed in spermatid and spermatozoa of the human testis. Remarkably, MAEL was located in the mitochondria of ejaculated sperm, and bioinformatics analysis identified GPX4 and UBL4B as MAEL's downstream targets. Knockdown of MAEL sabotaged mitochondria function and reduced adenosine triphosphate (ATP) production in H358 cells. MAEL, GPX4, and UBL4B expression levels were significantly decreased in asthenozoospermic sperms than in controls. The MAEL protein levels were positively correlated with GPX4 and UBL4B in human sperm. Total motile sperm count (TMSC) was positively correlated with protein levels of MAEL, GPX4, and UBL4B in ejaculated sperms.We highlight prominent MAEL expression in the intratesticular spermatid and the mitochondria of ejaculated spermatozoa. MAEL directly binds to GPX4 and UBL4B, and loss of MAEL induces mitochondrial dysfunction. MAEL-mitochondrial function-motility relationship might advance our understanding of the causes of asthenozoospermia.

Spermatid

Spermatocyte

10.1111/andr.13408

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Citations (1)

LRWD1 Regulates Microtubule Nucleation and Proper Cell Cycle Progression in the Human Testicular Embryonic Carcinoma Cells

Journal of Cellular Biochemistry (2017)

Chia‐Yih Wang Yu‐Han Hong Jhih‐Siang Syu Yung‐Chieh Tsai Xiuying Liu

Leucine-rich repeats and WD repeat domain containing protein 1 (LRWD1) is a testis-specific protein that mainly expressed in the sperm neck where centrosome is located. By using microarray analysis, LRWD1 is identified as a putative gene that involved in spermatogenesis. However, its role in human male germ cell development has not been extensively studied. When checking in the semen of patients with asthenozoospermia, teratozoospermia, and asthenoteratozoospermia, the level of LRWD1 in the sperm neck was significantly reduced with a defective neck or tail. When checking the sub-cellular localization of LRWD1 in the cells, we found that LRWD1 resided in the centrosome and its centrosomal residency was independent of microtubule transportation in NT2/D1, the human testicular embryonic carcinoma, cell line. Depletion of LRWD1 did not induce centrosome re-duplication but inhibited microtubule nucleation. In addition, the G1 arrest were observed in LRWD1 deficient NT2/D1 cells. Upon LRWD1 depletion, the levels of cyclin E, A, and phosphorylated CDK2, were reduced. Overexpression of LRWD1 promoted cell proliferation in NT2/D1, HeLa, and 239T cell lines. In addition, we also observed that autophagy was activated in LRWD1 deficient cells and inhibition of autophagy by chloroquine or bafilomycin A1 promoted cell death when LRWD1 was depleted. Thus, we found a novel function of LRWD1 in controlling microtubule nucleation and cell cycle progression in the human testicular embryonic carcinoma cells. J. Cell. Biochem. 119: 314-326, 2018. © 2017 Wiley Periodicals, Inc.

Carcinoma Cell

10.1002/jcb.26180

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Citations (13)

Validation and simplification of Fournier's gangrene severity index

International Journal of Urology (2014)

Tsung‐Yen Lin Chien‐Hui Ou Tzong‐Shin Tzai Yat‐Ching Tong C.-C. Chang

Objectives To validate the predictive value of F ournier's G angrene S everity I ndex in patients with F ournier gangrene and to facilitate patient mortality risk‐stratification by simplifying the F ournier's G angrene S everity I ndex. Methods From J anuary 1989 to D ecember 2011, 85 male patients with clinically‐documented F ournier's gangrene undergoing intensive treatment and with complete medical records were recruited. The demographic information and nine parameters of F ournier's G angrene S everity I ndex were compared between survivors and non‐survivors. The parameters that showed a significant difference between the two groups were selected to generate a simplified scoring index. Results Of the 85 patients recruited, 16 patients died of the disease with mortality rate of 18.8%. The F ournier's G angrene S everity I ndex score at initial diagnosis was significantly higher in non‐survivors than in survivors. Of the nine parameters of F ournier's G angrene S everity I ndex, the scores of serum creatinine level, hematocrit level and serum potassium level were significantly different between the two groups. However, the mean body temperatures, heart rate, respiration rate, white blood cell count, serum sodium and bicarbonate levels were non‐significantly different. Of the 12 patients with chronic kidney disease or end‐stage renal disease, 10 died of severe sepsis. A simplified scoring index including parameters of creatinine, hematocrit and potassium was generated, which provided sensitivity and specificity of 87% and 77% in predicting patient mortality, respectively. The predictive values of this simplified F ournier's G angrene S everity I ndex were shown to be non‐inferior to F ournier's G angrene S everity I ndex in our patients. Conclusions The simplified F ournier's G angrene S everity I ndex is easy to use at initial diagnosis, and offers a way to compare outcomes in different clinical populations.

White blood cell

Gangrene

10.1111/iju.12426

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Citations (62)

Stimulatory action of epidermal growth factor (EGF) on bovine oocyte maturation in serum free defined medium

Theriogenology (1990)

Atsushi Sanbuissho Serdar Coşkun Yung‐Ming Lin

Germinal vesicle

In vitro maturation

Follicular fluid

10.1016/0093-691x(90)90742-c

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Citations (4)

Bone morphogenetic protein 6 affects cell-cell communication by altering the expression of Connexin43 in human granulosa-lutein cells

Molecular and Cellular Endocrinology (2019)

Haicui Wu Hsun‐Ming Chang Yuyin Yi Zhen‐Gao Sun Yung‐Ming Lin

Granulosa cell

10.1016/j.mce.2019.110548

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Citations (8)

UPREGULATION OF MIR-630 BY HEAT SHOCK LEADS TO DECREASED SOX30 EXPRESSION IN SPERMATOGENESIS

Journal of Andrology (2012)

Yung‐Ming Lin Chia-Ling Chung Hsiu-Yen Ma Chun-Wun Lu

Expression (computer science)

Source

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Citations (0)

Incorporating Simplified Fournier's Gangrene Severity Index with early surgical intervention can maximize survival in high‐risk Fournier's gangrene patients

International Journal of Urology (2019)

Tsung‐Yen Lin I‐Hung Cheng Chien‐Hui Ou Yuh‐Shyan Tsai Yat‐Ching Tong

To determine the optimal surgical timing in high-risk patients with Fournier's gangrene by the Simplified Fournier's Gangrene Severity Index.From 1989 to 2018, 118 male patients diagnosed with Fournier's gangrene with complete medical records were retrospectively reviewed. Patients' demographics, laboratory parameters at initial diagnosis, Fournier's Gangrene Severity Index and Simplified Fournier's Gangrene Severity Index, and the time interval from emergency room arrival to surgical intervention were collected. The Fournier's gangrene patients were categorized into low-risk (Simplified Fournier's Gangrene Severity Index ≤2) and high-risk groups (Simplified Fournier's Gangrene Severity Index >2). Differences between the variables within the two groups were analyzed. The optimal surgical timing was analyzed with the receiver operating characteristic curve in high-risk Fournier's gangrene patients.The overall mortality of 118 Fournier's gangrene patients was 14.4%. After risk stratification with the Simplified Fournier's Gangrene Severity Index scoring system, the mortality of low-risk and high-risk Fournier's gangrene patients was 1.3% and 41.0%, respectively. In the high-risk group, the time interval from emergency room arrival to surgical intervention was the only variable with a significant difference between survivors and non-survivors (P = 0.039). The optimal surgical timing was determined at 14.35 h, which allowed the highest sensitivity (0.688) and specificity (0.762) to affect mortality. The mortality was significantly lower in high-risk Fournier's gangrene patients with early surgical intervention compared with late intervention (23.8% vs 68.8%, P = 0.007).The Simplified Fournier's Gangrene Severity Index is a quick and reliable screening tool for first-line physicians to identify high-risk patients with Fournier's gangrene (Simplified Fournier's Gangrene Severity Index >2) who have poor survival outcomes. We recommended early surgical intervention within 14.35 h to maximize the survival of high-risk Fournier's gangrene patients.

Gangrene

Fournier gangrene

Risk Stratification

10.1111/iju.13989

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Citations (31)

TGF-β1 promotes vitamin D-induced prostaglandin E2 synthesis by upregulating vitamin D receptor expression in human granulosa-lutein cells

AJP Endocrinology and Metabolism (2020)

Fuxin Wang Hsun‐Ming Chang Yuyin Yi Yung‐Ming Lin Hong Li

There is increasing evidence showing the importance of vitamin D (Vit D) and its nuclear receptor, the Vit D receptor (VDR), in female reproductive health. Transforming growth factor-β1 (TGF-β1) and its functional receptors are expressed in human oocytes and granulosa cells that participate in follicular development and ovulation. Recently, Sma- and Mad-related protein 3 (SMAD3; a downstream effector of TGF-β1) has been proposed to mediate crosstalk between the Vit D and TGF-β1 signaling pathways, but this relationship has not been fully explored and has yet to be tested in human granulosa-lutein (hGL) cells. In this study, we showed that TGF-β1 significantly promoted the expression of VDR, and this stimulatory effect occurred through the activin receptor-like kinase 5 type I receptor-mediated SMAD3 and ERK1/2 signaling pathways in hGL cells. Additionally, we showed that Vit D increased the expression of cyclooxygenase 2 (COX-2) and the synthesis of prostaglandin E2 (PGE2) in a time- and dose-dependent manner. Furthermore, we demonstrated a synergistic effect of TGF-β1 and Vit D on the expression of COX-2 and synthesis of PGE2, and this effect could be attenuated by silencing the expression of VDR. Our findings indicate that TGF-β1 upregulates the expression of VDR, which promotes Vit D-induced COX-2 expression and subsequent PGE2 production by activating the SMAD3 and ERK1/2 signaling pathways in hGL cells.

Prostaglandin E2 receptor

10.1152/ajpendo.00361.2019

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Citations (13)

LRWD1 expression is regulated through DNA methylation in human testicular embryonal carcinoma cells

Basic and Clinical Andrology (2021)

Jui‐Hsiang Hung Han‐Yi Cheng Yung-Chieh Tsai Hsien-An Pan Hany A. Omar

Abstract Background Sperm growth and maturation are correlated with the expression levels of Leucine-rich repeat and WD repeat-containing protein 1 (LRWD1), a widely expressed protein in the human testicles. The decrease in LRWD1 cellular level was linked to the reduction in cell growth and mitosis and the rise in cell microtubule atrophy rates. Since DNA methylation has a major regulatory role in gene expression, this study aimed at exploring the effect of the modulation of DNA methylation on LRWD1 expression levels. Results The results revealed the presence of a CpG island up of 298 bps (− 253 ~ + 45) upon LRWD1 promoter in NT2/D1 cells. The hypermethylation of the LRWD1 promoter was linked to a reduction in the transcription activity in NT2/D1 cells, as indicated by luciferase reporter assay. The methylation activator, floxuridine, confirmed the decrease in the LRWD1 promoter transcriptional activity. On the other hand, 5-Aza-2′-deoxycytidine (5-Aza-dc, methylation inhibitor), significantly augmented LRWD1 promoter activity and the expression levels of mRNA and proteins. Furthermore, DNA methylation status of LRWD1 promoter in human sperm genomic DNA samples was analyzed. The results indicated that methylation of LRWD1 promoter was correlated to sperm activity. Conclusions Thus, the regulation of LRWD1 expression is correlated with the methylation status of LRWD1 promoter, which played a significant role in the modulation of spermatogenesis, sperm motility, and vitality. Based on these results, the methylation status of LRWD1 promoter may serve as a novel molecular diagnostic marker or a therapeutic target in males’ infertility.

CpG site

10.1186/s12610-021-00130-y

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Citations (6)