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Immunohistochemical measurement and expression of Mcl-1 in infertile testes

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《医学前沿(英文)》 2015年 第9卷 第3期   页码 361-367 doi: 10.1007/s11684-015-0395-x

摘要:

The diagnosis of azoospermia represents a major challenge to andrologists as this condition may occur despite normal spermatogenesis and genital tracts. Myeloid cell leukemia-1 (Mcl-1) is a member of the Bcl-2 family of proteins involved in regulation of apoptosis in various cell types. This study aimed to investigate the immunohistochemical expression of Mcl-1 in testicular biopsies of subjects with azoospermia. Eighty-six cases with azoospermia were obtained from 509 infertile patients admitted to the Andrology Unit of the Zagazig University Hospitals from January 2010 to December 2011. Biopsies were diagnosed and classified using H&E-stained slide sections. The specimens were subjected to immunohistochemical staining for Mcl-1 and examined through light microscopy. Forty-five cases of maturation arrest (25 at spermatids and 20 at the spermatocytes), 31 cases of hypospermatogenesis (20 moderate and 11 severe), 5 cases of Sertoli?cell-only syndrome, 2 cases of basement membrane hyalinization, and 1 case of tubular and peritubular sclerosis were observed. Normal spermatogenesis was detected in 2 cases. A strong positive immunoreaction in Leydig cells was observed among all investigated specimens. A moderate reaction was detected in spermatocytes and spermatozoa in cases of normal spermatogenesis and hypospermatogenesis, but a negative reaction was detected in cases of maturation arrest and germ cell aplasia. Apoptosis was found to be associated with decreased rate of spermatogenesis. High apoptosis rates may result in azoospermia, which can occur despite normal spermatogenesis and absence of duct obstruction.

关键词: spermatogenesis     testis     Mcl-1 expression     immunohistochemical study     infertility    

Physiological functions and clinical implications of the N-end rule pathway

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《医学前沿(英文)》 2016年 第10卷 第3期   页码 258-270 doi: 10.1007/s11684-016-0458-7

摘要:

The N-end rule pathway is a unique branch of the ubiquitin-proteasome system in which the determination of a protein’s half-life is dependent on its N-terminal residue. The N-terminal residue serves as the degradation signal of a protein and thus called N-degron. N-degron can be recognized and modifed by several steps of post-translational modifications, such as oxidation, deamination, arginylation or acetylation, it then polyubiquitinated by the N-recognin for degradation. The molecular basis of the N-end rule pathway has been elucidated and its physiological functions have been revealed in the past 30 years. This pathway is involved in several biological aspects, including transcription, differentiation, chromosomal segregation, genome stability, apoptosis, mitochondrial quality control, cardiovascular development, neurogenesis, carcinogenesis, and spermatogenesis. Disturbance of this pathway often causes the failure of these processes, resulting in some human diseases. This review summarized the physiological functions of the N-end rule pathway, introduced the related biological processes and diseases, with an emphasis on the inner link between this pathway and certain symptoms.

关键词: N-end rule pathway     Ate1     cardiovascular development     neurogenesis     spermatogenesis     neurodegenerative disorders     Johanson–Blizzard syndrome    

DDB1- and CUL4-associated factor 8 plays a critical role in spermatogenesis

Xiuli Zhang, Zhizhou Xia, Xingyu Lv, Donghe Li, Mingzhu Liu, Ruihong Zhang, Tong Ji, Ping Liu, Ruibao Ren

《医学前沿(英文)》 2021年 第15卷 第2期   页码 302-312 doi: 10.1007/s11684-021-0851-8

摘要: Cullin-RING E3 ubiquitin ligase (CRL)-4 is a member of the large CRL family in eukaryotes. It plays important roles in a wide range of cellular processes, organismal development, and physiological and pathological conditions. DDB1- and CUL4-associated factor 8 (DCAF8) is a WD40 repeat-containing protein, which serves as a substrate receptor for CRL4. The physiological role of DCAF8 is unknown. In this study, we constructed knockout mice. Homozygous mice were viable with no noticeable abnormalities. However, the fertility of deficient male mice was markedly impaired, consistent with the high expression of DCAF8 in adult mouse testis. Sperm movement characteristics, including progressive motility, path velocity, progressive velocity, and track speed, were significantly lower in knockout mice than in wild-type (WT) mice. However, the total motility was similar between WT and knockout sperm. More than 40% of spermatids in knockout mice showed pronounced morphological abnormalities with typical bent head malformation. The acrosome and nucleus of knockout sperm looked similar to those of WT sperm. tests showed that the fertilization rate of knockout mice was significantly reduced. The results demonstrated that DCAF8 plays a critical role in spermatogenesis, and DCAF8 is a key component of CRL4 function in the reproductive system.

关键词: Dcaf8     male infertility     spermatogenesis    

标题 作者 时间 类型 操作

Immunohistochemical measurement and expression of Mcl-1 in infertile testes

null

期刊论文

Physiological functions and clinical implications of the N-end rule pathway

null

期刊论文

DDB1- and CUL4-associated factor 8 plays a critical role in spermatogenesis

Xiuli Zhang, Zhizhou Xia, Xingyu Lv, Donghe Li, Mingzhu Liu, Ruihong Zhang, Tong Ji, Ping Liu, Ruibao Ren

期刊论文