scholarly journals YBX2 Dysregulation in Maturation Arrest NOA YBX2 Dysregulation is a Potential Cause for Late Maturation Arrest in Men with Non-Obstructive Azoospermia

2018 ◽  
Author(s):  
Ryan Flannigan ◽  
Anna Mielnik ◽  
Brian D. Robinson ◽  
Francesca Khani ◽  
Alex Bolyakov ◽  
...  
Keyword(s):  
Human Testis ◽  
Obstructive Azoospermia ◽  
Maturation Arrest ◽  
Knock Out ◽  
Tissue Sections ◽  
Pachytene Spermatocytes ◽  
Late Maturation ◽  
Normal Controls ◽  
Translational Suppression ◽  
Testis Tissue

AbstractIntroductionYBX2 protein binds to Y-box promotors and to mRNAs in the cytoplasm of pachytene spermatocytes and round spermatids in rodents. Knock-out of YBX2 leads to maturation arrest in animal models. YBX2 binds PRM1 and 2 mRNA, which is transcribed early and sequestrated for translation during late spermatogenesis.ObjectiveThis study aimed to determine if the loss of YBX2 is associated with MA arrest due to the loss of sequestration of protamines in the human testis. As a second aim, we examined the expression of YBX2, and its transcription factors in maturation arrest (MA)(early and late) and normal controls in men.MethodsRNAseq was performed using RNA extracted from human testis samples from 44 men with non-obstructive azoospermia and ten from healthy controls. Differential expression was performed using JMPgenomics, FDR<0.001. FANTOM5 was used to predict enhancers and inhibitors of YBX2 expression. Immunofluorescence (IF) was used to stain testis tissue sections with antibodies against YBX2, SYCP3, and PRM2 in normal and MA samples. Flow cytometry was utilized to characterize YBX2 positive cells.ResultsExpression of YBX2 mRNA was significantly downregulated in early and late MA compared to controls. Surprisingly, PRM1&2 mRNAs were also depleted in men with MA. Multifactorial regression analysis demonstrated a decrease in YBX2 expression in MA is due to decrease in COMP levels (p<0.0001). IF localized YBX2 protein in spermatocytes and round spermatids among fertile men, with rare YBX2 positive spermatocytes stained in LMA. PRM1&2 proteins were absent or abnormally sequestrated within spermatocytes.ConclusionsDecrease in YBX2 protein expression in men with LMA leads to loss of translational suppression and lack of PRM1 and PRM2 necessary to complete spermatogenesis.

Postchemotherapy Ejaculatory Azoospermia: Fatherhood With Sperm From Testis Tissue With Intracytoplasmic Sperm Injection

2002 ◽  
Vol 20 (4) ◽  
pp. 930-936 ◽  
Author(s):  
M. N. Damani ◽  
V. Masters ◽  
M. V. Meng ◽  
C. Burgess ◽  
P. Turek ◽  
...  
Keyword(s):  
Intracytoplasmic Sperm Injection ◽  
Fertilization Rate ◽  
Nonobstructive Azoospermia ◽  
Fresh Tissue ◽  
Icsi Cycle ◽  
Small Subgroup ◽  
History Of ◽  
Fertility Potential ◽  
Late Maturation ◽  
Testis Tissue

PURPOSE: To define the success of testis sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) in azoospermic men with a history of chemotherapy. PATIENTS AND METHODS: In a retrospective study, 23 men with ejaculatory azoospermia and a history of chemotherapy underwent TESE in a search for usable spermatozoa. In six patients cryopreserved tissue and in nine patients fresh tissue provided sperm for an ICSI cycle. Histologic analysis of the testis was performed in all patients. The presence or absence of sperm, fertilization rates with ICSI, and final outcomes of pregnancy were recorded. RESULTS: Spermatozoa were found on TESE in 15 (65.2%) of 23 men. On histopathology, the predominant pattern observed was Sertoli cell only (47.8%), followed by hypospermatogenesis (30.4%), mixed (17.4%), and late maturation arrest (4.3%). The fertilization rate was 65.2%, and ongoing/delivered pregnancies occurred in 30.8% of cycles. Six healthy boys and four healthy girls have been born to date. CONCLUSION: Men who are azoospermic and have had prior cytotoxic therapy make up a small subgroup of males with nonobstructive azoospermia. It is important to define and characterize this subgroup and better define their true fertility potential. Approximately two thirds of these men have retrievable testis sperm, which may be used with ICSI to have healthy offspring. This exciting avenue for paternity has heretofore not been available to such patients.

scholarly journals Germ cell fate and seminiferous tubule development in bovine testis xenografts

Reproduction ◽  
2005 ◽  
Vol 130 (6) ◽  
pp. 923-929 ◽  
Author(s):  
Rahul Rathi ◽  
Ali Honaramooz ◽  
Wenxian Zeng ◽  
Stefan Schlatt ◽  
Ina Dobrinski
Keyword(s):  
Germ Cell ◽  
Cell Fate ◽  
Germ Cells ◽  
Cell Number ◽  
Sperm Production ◽  
Continuous Increase ◽  
Control Tissue ◽  
Low Efficiency ◽  
Pachytene Spermatocytes ◽  
Testis Tissue

Spermatogenesis can occur in testis tissue from immature bulls ectopically grafted into mouse hosts; however, efficiency of sperm production is lower than in other donor species. To elucidate a possible mechanism for the impaired spermatogenesis in bovine testis xenografts, germ cell fate and xenograft development were investigated at different time points and compared with testis tissue from age-matched calves as controls. Histologically, an initial decrease in germ cell number was noticed in xenografts recovered up to 2 months post-grafting without an increase in germ cell apoptosis. From 2 months onward, the number of germ cells increased. In contrast, a continuous increase in germ cell number was seen in control tissue. Pachytene spermatocytes were observed in some grafts before 4 months, whereas in the control tissue they were not present until 5 months of age. Beyond 4 months post-grafting spermatogenesis appeared to be arrested at the pachytene spermatocyte stage in most grafts. Elongated spermatids were observed between 6 and 8 months post-grafting, similar to the controls, albeit in much lower numbers. Lumen formation started earlier in grafts compared with controls and by 6 months post-grafting tubules with extensively dilated lumen were observed. A donor effect on efficiency of spermatogenesis was also observed. These results indicate that the low efficiency of sperm production in bovine xenografts is due to an initial deficit of germ cells and impaired meiotic and post-meiotic differentiation. The characterization of spermatogenic efficiency will provide the basis to understand the control of spermatogenesis in testis grafts.

TESTIS TISSUE ALLOGRAFTING REVEALS A PHENOTYPE OF MEIOTIC ARREST IN NEONATALLY LETHAL LSH KNOCK OUT MICE

2007 ◽  
Vol 77 (Suppl_1) ◽  
pp. 187-187
Author(s):  
Wenxian Zeng ◽  
Ali Honaramooz ◽  
Tao Fan ◽  
Anja Schmidtmann ◽  
Claudia Baumann ◽  
...  
Keyword(s):  
Meiotic Arrest ◽  
Knock Out ◽  
Knock Out Mice ◽  
Testis Tissue

scholarly journals Distribution of the sex chromosome during mouse spermatogenesis in testis tissue sections

2015 ◽  
Vol 61 (5) ◽  
pp. 375-381 ◽  
Author(s):  
Kosuke OTAKA ◽  
Yuuki HIRADATE ◽  
Norio KOBAYASHI ◽  
Yoshiki SHIRAKATA ◽  
Kentaro TANEMURA
Keyword(s):  
Sex Chromosome ◽  
Tissue Sections ◽  
Testis Tissue

scholarly journals Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility Preservation

2020 ◽  
Vol 9 (1) ◽  
pp. 266 ◽  
Author(s):  
Marsida Hutka ◽  
Lee B. Smith ◽  
Ellen Goossens ◽  
W. Hamish B. Wallace ◽  
Jan-Bernd Stukenborg ◽  
...  
Keyword(s):  
Sertoli Cell ◽  
Sertoli Cells ◽  
Connexin 43 ◽  
Xenograft Model ◽  
Cell Maturation ◽  
Human Testis ◽  
Testicular Development ◽  
Future Fertility ◽  
And Function ◽  
Testis Tissue

The future fertility of prepubertal boys with cancer may be irreversibly compromised by chemotherapy and/or radiotherapy. Successful spermatogenesis has not been achieved following the xenotransplantation of prepubertal human testis tissue, which is likely due to the failure of somatic cell maturation and function. We used a validated xenograft model to identify the factors required for Leydig and Sertoli cell development and function in immature human testis. Importantly, we compared the maturation status of Sertoli cells in xenografts with that of human testis tissues (n = 9, 1 year-adult). Human fetal testis (n = 6; 14–21 gestational weeks) tissue, which models many aspects of prepubertal testicular development, was transplanted subcutaneously into castrated immunocompromised mice for ~12 months. The mice received exogenous human chorionic gonadotropin (hCG; 20IU, 3×/week). In xenografts exposed continuously to hCG, we demonstrate the maintenance of Leydig cell steroidogenesis, the acquisition of features of Sertoli cell maturation (androgen receptor, lumen development), and the formation of the blood–testis barrier (connexin 43), none of which were present prior to the transplantation or in xenografts in which hCG was withdrawn after 7 months. These studies provide evidence that hCG plays a role in Sertoli cell maturation, which is relevant for future investigations, helping them generate functional gametes from immature testis tissue for clinical application.

scholarly journals Early Versus Late Maturation Arrest: Reproductive Outcomes of Testicular Failure

2011 ◽  
Vol 186 (2) ◽  
pp. 621-626 ◽  
Author(s):  
John W. Weedin ◽  
Richard C. Bennett ◽  
David M. Fenig ◽  
Dolores J. Lamb ◽  
Larry I. Lipshultz
Keyword(s):  
Reproductive Outcomes ◽  
Maturation Arrest ◽  
Testicular Failure ◽  
Late Maturation

scholarly journals Analysis of STAG3 variants in Chinese non-obstructive azoospermia patients with germ cell maturation arrest

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wen Liu ◽  
Xuan Gao ◽  
Haobo Zhang ◽  
Ran Liu ◽  
Yongzhi Cao ◽  
...  
Keyword(s):  
Germ Cell ◽  
Male Meiosis ◽  
Cell Maturation ◽  
Control Group ◽  
Obstructive Azoospermia ◽  
The Novel ◽  
Nucleotide Polymorphisms ◽  
Maturation Arrest ◽  
Ethnic Populations ◽  
Genotype Frequencies

AbstractSTAG3 is essential for male meiosis and testis of male Stag3−/− mice shows the histopathological type of germ cell maturation arrest (MA). Whether variants of the STAG3 gene exist in Chinese idiopathic non-obstructive azoospermia (NOA) patients needs to be determined. We recruited 58 Chinese NOA men with MA who underwent testis biopsy and 192 fertile men as the control group. The 34 exons of the STAG3 gene were amplified using polymerase chain reaction (PCR) and sequenced. We identified eight novel single nucleotide polymorphisms (SNPs), including two missense SNPs (c.433T > C in exon2 and c.553A > G in exon3), three synonymous SNPs (c.539G > A, c.569C > T in exon3, and c.1176C > G in exon8), and three SNPs in introns. The allele and genotype frequencies of the novel and other SNPs have no significant differences between two groups. Our results indicated that variants in the coding sequence of the STAG3 gene were uncommon in NOA patients with MA in Chinese population. Future studies in large cohorts of different ethnic populations will be needed to determine the association between the STAG3 gene and NOA.

Hematopoietic Specific GATA-1-Improved Cre Mouse for Erythroid-Specific Gene Modification.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1291-1291
Author(s):  
Donghoon Yoon ◽  
Bumjun Kim ◽  
Myunghi Kwon ◽  
Josef T. Prchal
Keyword(s):  
Bone Marrow ◽  
Transgenic Mouse ◽  
Erythropoietin Receptor ◽  
Specific Gene ◽  
Hematopoietic Tissue ◽  
Knock Out ◽  
Tissue Sections ◽  
Lacz Staining ◽  
Splenic Cells ◽  
Beta Galactosidase

Abstract Animal models of erythropoiesis related genes have been limited by the fact that some of these genes have non-erythroid expression and other functions in addition to erythropoiesis and thus their knock-out may be embryonic lethal. Tissue specific knock-out or knock-in mice models employing GATA-1-Cre and other constructs showed that these promoters are also active in non-hematopoietic tissues, i.e. GATA-1 has activity in early embryonic development and in neuronal tissue. Suzuki et al (Blood, 2002, 100; 2279) isolated the GATA-1 locus hematopoietic regulatory domain (GATA-1-HRD) and demonstrated that the expression of a transgene under its control is limited to the hematopoietic tissue. We generated a transgenic mouse expressing an improved Cre (iCre) under GATA-1-HRD promoter control. This mouse was crossbred with ROSA 26 mouse and the progeny was examined for tissue specificity of iCre expression using beta-galactosidase staining. Brain, spleen, kidney, heart, thymus, liver, lung and ovary were examined for whole organ LacZ staining. All tested organs were negative except kidney and spleen where some positivity was observed. Subsequently, we prepared tissue sections from kidney, spleen and bone marrow and stained with LacZ and anti-beta-galactosidase antibody. Only the bone marrow EpoR expressing cells were positive; the kidney and the spleen cells were negative. Although Suzuki et al previously showed expression of the GATA-1-HRD driven erythropoietin receptor in spleen using RT-PCR, we were not able to find iCre expression in the splenic cells using these approaches. We demonstrate that our transgenic mouse (GATA-1-HRD-iCre) showed a restricted iCre expression in hematopoietic tissue that differs from previous studies of other hematopoiesis specific cre mouse. We conclude that this mouse model should be useful in studies of function of erythroid specific genes.

Inhibition of 16α-hydroxylation in human testis tissue by SU-9055

Steroids ◽  
1966 ◽  
Vol 8 (1) ◽  
pp. 25-32 ◽  
Author(s):  
John C. Colla ◽  
Joseph P. Liberti ◽  
Frank Ungar
Keyword(s):  
Human Testis ◽  
Testis Tissue
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