Genetic pathogenesis of acephalic spermatozoa syndrome: past, present, and future / 亚洲男科学杂志(英文版)

Acephalic spermatozoa syndrome (ASS) is one of the most severe spermatogenic failures of all infertility in men. The cognition of ASS has experienced a tortuous process. Over the past years, with the in-depth understanding of spermatogenesis and the emergence of new genetic research technologies, the unraveling of the genetic causes of spermatogenic failure has become highly active. From these advances, we established a genetic background and made significant progress in the discovery of the genetic causes of ASS. It is important to identify pathogenic genes and mutations in ASS to determine the biological reasons for the occurrence of the disease as well as provide genetic diagnosis and treatment strategies for patients with this syndrome. In this review, we enumerate various technological developments, which have made a positive contribution to the discovery of candidate genes for ASS from the past to the present. Simultaneously, we summarize the known genetic etiology of this phenotype and the clinical outcomes of treatments in the present. Furthermore, we propose perspectives for further study and application of genetic diagnosis and assisted reproductive treatment in the future.

Novel DPY19L2 variants in globozoospermic patients and the overcoming this male infertility / 亚洲男科学杂志(英文版)

Globozoospermia has been reported to be a rare but severe causation of male infertility, which results from the failure of acrosome biogenesis and sperm head shaping. Variants of dpy-19-like 2 (DPY19L2) are highly related to globozoospermia, but related investigations have been mainly performed in patients from Western countries. Here, we performed a screening of DPY19L2 variants in a cohort of Chinese globozoospermic patients and found that five of nine patients carried DPY19L2 deletions and the other four patients contained novel DPY19L2 point mutations, as revealed by whole-exome sequencing. Patient 3 (P3) contained a heterozygous variant (c.2126+5G>A), P6 contained a homozygous nonsense mutation (c.1720C>T, p.Arg574*), P8 contained compound heterozygous variants (c.1182-1184delATC, p.Leu394_Ser395delinsPhe; c.368A>T, p.His123Arg), and P9 contained a heterozygous variant (c.1182-1184delATCTT, frameshift). We also reported intracytoplasmic sperm injection (ICSI) outcomes in the related patients, finding that ICSI followed by assisted oocyte activation (AOA) with calcium ionophore achieved high rates of live births. In summary, the infertility of these patients results from DPY19L2 dysfunction and can be treated by ICSI together with AOA.

Abnormalities of meiotic recombination in Han Chinese azoospermic patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze defective homologous chromosomal recombination in Han Chinese azoospermic patients.</p><p><b>METHODS</b>Testicular biopsy samples from 7 healthy controls and 7 Han Chinese azoospermic patients including 2 obstructive azoospermia (OA group) and 5 non-obstructive azoospermia (NOA group) were analyzed. Immunofluorescence staining was performed to categorize early stage cells at meiosis prophase and to analyze chromosome pairing and recombination of pachytene spermatocyte. Newly developed meiotic proteins antibodies (anti-SCP3, anti-synaptonemal complex proteins 3, anti-MLH1, anti-Mut-L Homolog 1, anti-CREST, chromosome centromere antibody) were used to identify synaptonemal complex (anti-SCP3), recombination sites (anti-MLH1) and centromere (anti-CREST), respectively. Staging of spermatocyte was determined according to SCP3 formation progression. Qualitative data were compared by a Chi-square test, and ANOVA was used to analyze quantitative data.</p><p><b>RESULTS</b>Respectively, 2346 and 2932 spermatocytes were categorized in the controls and azoospermic patients. The proportions of zygotene cells in both OA group and NOA group were significantly higher than that of the control group. Investigation of 1967 pachytene cells from the controls and 354 pachytene cells from azoospermic patients indicated that the mean MLH1 foci per pachytene cell of NOA group was statistically lower than that of the controls. Compared with the controls, incomplete synaptonemal complexes cells (containing gap and/or split) were significantly increased in the NOA group.</p><p><b>CONCLUSION</b>Delayed meiosis prophase is relatively common in azoospermic patients, and changes in quantity and distribution of recombination foci may be the cause for spermatogenesis arrest in Han Chinese population.</p>

Compound Xuanju Capsule combined with vitamin E improves sperm chromatin integrity / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the clinical effects of the combined therapy of the Chinese medicine Compound Xuanju Capsule and vitamin E on sperm chromatin damage in idiopathic oligoasthenospermia.</p><p><b>METHODS</b>We assigned 50 infertile men with seminal abnormality to a control group (n = 26) and a trial group (n = 24) to receive vitamin E and the combined therapy of Compound Xuanju Capsule plus vitamin E, respectively, both treated for 3 months. Before and after the treatment, we detected semen routine parameters and sperm DNA fragmentation indexes (DFI) by computer aided semen analysis (CASA) and sperm chromatin structure assay (SCSA), and compared them between the two groups.</p><p><b>RESULTS</b>There was no obvious difference between the percentage of progressively motile sperm in the trial group and that in the control group (21.55 +/- 8.68 vs 21.47 +/- 11.53, P > 0.05). The trial group showed a significantly decreased sperm DFI after medication as compared with pre-medication (29.57 +/- 12.19 vs 34.09 +/- 10.32, P < 0.05).</p><p><b>CONCLUSION</b>The combined therapy of Compound Xuanju Capsule and vitamin E can effectively improve seminal quality and reduce sperm chromatin damage in infertile men with idiopathic oligoasthenospermia.</p>

Sperm chromatin integrity test for predicting the outcomes of IVF and ICSI / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the predictive value of sperm chromatin integrity test (SCIT) in assisted reproductive technology (ART) by analyzing the relationship of sperm chromatin integrity (SCI) with the outcomes of IVF-ET and ICSI.</p><p><b>METHODS</b>Sperm chromatin structure assay (SCSA) was performed to test SCI in 187 ART cycles, and the results were expressed as DNA fragmentation index (DFI). According to the level of DFI, the 187 cycles were allocated to a high DFI group (DFI > or = 30% ) and a low DFI group (DFI < 30%), each of which was again divided into an IVF and an ICSI subgroup. Comparisons were made between the IVF and ICSI subgroups of the high and low DFI groups in the fertilization rate, cleavage rate, embryo quality, and clinical pregnancy rate.</p><p><b>RESULTS</b>The clinical pregnancy rate of ICSI was significantly higher than that of IVF in the high DFI group, while the clinical outcomes showed no significant differences between the high and low DFI groups in either the IVF or the ICSI subgroup.</p><p><b>CONCLUSION</b>Sperm DNA damage affects the outcome of ART, and therefore SCIT can be used as a supplementary option to standard semen analysis in choosing the method for ART.</p>