A novel partial deletion of the Y chromosome azoospermia factor c region is caused by non-homologous recombination between palindromes and may be associated with increased sperm counts

Abstract Background The purpose of this study is to evaluate the prognostic factors for sperm retrieval and determine if Y chromosome deletion is associated with deleterious effects. Whether Y chromosome deletion determines the sperm retrieval rate in non-mosaic Klinefelter patients has not yet been addressed. Methods We retrospectively collected medical records of azoospermic patients from Sep 2009 to Dec 2018, and enrolled 66 non-mosaic 47, XXY patients who were receiving mTESE. The predictive values of patients age, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, prolactin, estradiol and Y chromosome deletion were assessed for successful sperm recovery. Results Testicular sperm recovery was successful in 24 (36.4%) of 66 men. The mean age (36.0 vs. 36.6 years), and levels of FSH (30.0 vs 36.9 IU/L), LH (17.7 vs 21.9 IU/L), testosterone (2.4 vs. 2.1 ng/ml), prolactin (9.1 vs. 8.8 ng/ml), and estradiol (19.4 vs. 22.3 pg/ml) did not show any significant difference when comparing patients with and without successful sperm retrieval. Partial deletion of azoospermic factor c (AZFc) was noted in 5 (20.8%) of 24 patients with successful sperm retrieval, including three b2/b3 and two gr/gr deletion cases, whereas 4 (9.5%) of 42 patients with unsuccessful sperm retrieval were noted to have AZFc partial deletion (one b2/b3 , one sY1206 and two gr/gr deletion), though the difference was not statistically significant (p=0.27) Conclusion According to present results, age and AZFc partial deletion status should not be a deterrent for azoospermic males with non-mosaic Klinefelter syndrome to undergo mTESE.

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Do partial AZFc deletions affect the sperm retrieval rate in non-mosaic Klinefelter patients undergoing microdissection testicular sperm extraction?

10.21203/rs.2.15379/v1 ◽

2019 ◽

Author(s):

I-Shen Huang ◽

Richard J Fantus ◽

Wei-Jen Chen ◽

James Wren ◽

Wei-Tang Kao ◽

...

Keyword(s):

Y Chromosome ◽

Testicular Sperm Extraction ◽

Chromosome Deletion ◽

Testicular Sperm ◽

Partial Deletion ◽

Sperm Retrieval ◽

Predictive Values ◽

Retrieval Rate ◽

Significant Difference ◽

Factor C

Abstract Background The purpose of this study is to evaluate the prognostic factors for sperm retrieval and determine if Y chromosome deletion is associated with deleterious effects. Whether Y chromosome deletion determines the sperm retrieval rate in non-mosaic Klinefelter patients has not yet been addressed.Methods We retrospectively collected medical records of azoospermic patients from Sep 2009 to Dec 2018, and enrolled 66 non-mosaic 47, XXY patients who were receiving mTESE. The predictive values of patients age, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, prolactin, estradiol and Y chromosome deletion were assessed for successful sperm recovery.Results Testicular sperm recovery was successful in 24 (36.4%) of 66 men. The mean age (36.0 vs. 36.6 years), and levels of FSH (30.0 vs 36.9 IU/L), LH (17.7 vs 21.9 IU/L), testosterone (2.4 vs. 2.1 ng/ml), prolactin (9.1 vs. 8.8 ng/ml), and estradiol (19.4 vs. 22.3 pg/ml) did not show any significant difference when comparing patients with and without successful sperm retrieval. Partial deletion of azoospermic factor c (AZFc) was noted in 5 (20.8%) of 24 patients with successful sperm retrieval, including three b2/b3 and two gr/gr deletion cases, whereas 4 (9.5%) of 42 patients with unsuccessful sperm retrieval were noted to have AZFc partial deletion (one b2/b3 , one sY1206 and two gr/gr deletion), though the difference was not statistically significant (p=0.27)Conclusion According to present results, age and AZFc partial deletion status should not be a deterrent for azoospermic males with non-mosaic Klinefelter syndrome to undergo mTESE.

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Analysis of DAZ gene expression in a partial AZFc deletion of the human Y chromosome

Reproduction Fertility and Development ◽

10.1071/rd12290 ◽

2014 ◽

Vol 26 (2) ◽

pp. 307 ◽

Cited By ~ 4

Author(s):

Byunghyuk Kim ◽

Wonkyung Lee ◽

Kunsoo Rhee ◽

Soo Woong Kim ◽

Jae-Seung Paick

Keyword(s):

Y Chromosome ◽

Pcr Assay ◽

Azfc Region ◽

Azoospermia Factor ◽

Azfc Deletion ◽

Deleted In Azoospermia ◽

Polymerase Chain ◽

Factor C ◽

Human Y Chromosome ◽

Daz Gene

The azoospermia factor c (AZFc) region of the Y chromosome consists of repetitive amplicons and is therefore highly susceptible to structural rearrangements, such as deletions and duplications. The b2/b3 deletion is a partial AZFc deletion that is conventionally determined by the selective absence of sY1191 in sequence-tagged site polymerase chain reaction (PCR) and is generally believed to retain two of the four deleted in azoospermia (DAZ) genes on the Y chromosome. In the present study we determined the copy number and expression of DAZ genes in sY1191-negative individuals. Using a DAZ dosage PCR assay and Southern blot analysis we evaluated the expression of four DAZ genes in five of six sY1191-negative individuals. Furthermore, cloning and immunoblot analyses revealed that three or more DAZ genes are expressed in sY1191-negative testes with germ cells. The results indicate that the selective absence of sY1191 not only means b2/b3 deletion with two DAZ genes, but also includes another AZFc configuration with four DAZ genes. These results exemplify the prevalence of variations in the AZFc region of the human Y chromosome.

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GR/GR deletions within the azoospermia factor c region on the Y chromosome might not be associated with spermatogenic failure

Fertility and Sterility ◽

10.1016/j.fertnstert.2005.07.1278 ◽

2006 ◽

Vol 85 (1) ◽

pp. 229-231 ◽

Cited By ~ 30

Author(s):

Celia Ravel ◽

Sandra Chantot-Bastaraud ◽

Brahim El Houate ◽

Jacqueline Mandelbaum ◽

Jean-Pierre Siffroi ◽

...

Keyword(s):

Y Chromosome ◽

Azoospermia Factor ◽

Factor C ◽

Spermatogenic Failure

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Azoospermia factor C subregion of the Y chromosome

Journal of Human Reproductive Sciences ◽

10.4103/jhrs.jhrs_16_17 ◽

2017 ◽

Vol 10 (4) ◽

pp. 256 ◽

Cited By ~ 5

Author(s):

JenabhaiB Chauhan ◽

Mili Nailwal

Keyword(s):

Y Chromosome ◽

Azoospermia Factor ◽

Factor C

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Decreased fertilization rate and embryo quality after ICSI in oligozoospermic men with microdeletions in the azoospermia factor c region of the Y chromosome

Human Reproduction ◽

10.1093/humrep/16.2.289 ◽

2001 ◽

Vol 16 (2) ◽

pp. 289-292 ◽

Cited By ~ 62

Author(s):

R. J.T. van Golde

Keyword(s):

Y Chromosome ◽

Embryo Quality ◽

Fertilization Rate ◽

Azoospermia Factor ◽

Factor C

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Inhibin B plasma concentrations in infertile patients with DAZ gene deletions treated with FSH

Acta Endocrinologica ◽

10.1530/eje.0.1460801 ◽

2002 ◽

pp. 801-806 ◽

Cited By ~ 6

Author(s):

C Foresta ◽

A Bettella ◽

E Moro ◽

M Rossato ◽

M Merico ◽

...

Keyword(s):

Y Chromosome ◽

Sertoli Cell ◽

Germ Cells ◽

Sertoli Cells ◽

Cell Function ◽

Plasma Concentrations ◽

Inhibin B ◽

Azoospermia Factor ◽

Deleted In Azoospermia ◽

Factor C

OBJECTIVE: The DAZ (deleted in azoospermia) gene family on the Y chromosome long arm is the major candidate for the AZFc (azoospermia factor c) phenotype of male infertility and it is expressed only in germ cells. The aim of the study was to assess Sertoli cell function in subjects with AZFc deletions. DESIGN: Case-control, prospective study. METHODS: We have studied six severely oligozoospermic subjects with AZFc-DAZ deletions, and looked whether they responded in terms of inhibin B production to a 1 month FSH treatment. These patients were compared with three groups of patients affected by different spermatogenic alterations not related to deletions on the Y chromosome. RESULTS: Although affected by severe testiculopathy, patients with AZFc-DAZ deletions had only slightly elevated FSH, and normal inhibin B plasma concentrations. Inhibin B responded normally during FSH treatment, supporting the hypothesis that Sertoli cells are not altered. On the contrary, other severe testiculopathies not related to Y chromosome deletions showed high FSH and low inhibin B concentrations, with no response to FSH treatment. In these cases the cause of the spermatogenic defect probably damaged both germ and Sertoli cells. Finally, idiopathic patients with a hormonal status similar to Y-deleted patients (slightly elevated FSH and normal inhibin B concentrations) did not respond to FSH treatment, suggesting that Sertoli cells were already at their maximal functional capability. CONCLUSIONS: These data confirm that Sertoli cell function is not damaged in patients with AZFc-DAZ deletions and that the strong reduction of germ cells does not affect the FSH-inhibin B feedback loop.

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