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Aging Jan 2024Oligoasthenoteratozoospermia (OAT) decreases male fertility, seriously affecting the production of offspring. This study clarified the preventive impact of different...
Oligoasthenoteratozoospermia (OAT) decreases male fertility, seriously affecting the production of offspring. This study clarified the preventive impact of different moxibustion frequencies on OAT and selected the optimal frequency to elucidate the underlying mechanism. An OAT rat model was constructed by gavage of tripterygium glycosides (TGS) suspension. Daily moxibustion (DM) or alternate-day moxibustion (ADM) was administered on the day of TGS suspension administration. Finally, we selected DM for further study based on sperm quality and DNA fragmentation index, testicular and epididymal morphology, and reproductive hormone level results. Subsequently, the oxidative stress (OS) status was evaluated by observing the OS indices levels; malondialdehyde (MDA), 8-hydroxy-deoxyguanosine (8-OHdG), total antioxidant capacity (T-AOC), and total superoxide dismutase (T-SOD) in testicular tissue using colorimetry and enzyme-linked immunosorbent assay. Furthermore, heme oxygenase 1 (HO-1) and nuclear factor erythropoietin-2-related factor 2 (Nrf2) were evaluated using Western blotting. Immunohistochemistry was employed to locate and assess the expression of HO-1 and Nrf2 protein, while quantitative real-time polymerase chain reaction was utilized to detect their mRNA expression. MDA and 8-OHdG levels decreased following DM treatment, while T-SOD and T-AOC increased, suggesting that DM may prevent TGS-induced OAT in rats by decreasing OS in the testis. Furthermore, protein and mRNA expression of Nrf2 and HO-1 in the testis were elevated, indicating that DM may reduce OS by activating the signaling pathway of Nrf2/HO-1. Therefore, DM could prevent OAT in rats via the Nrf2/HO-1 pathway, thereby presenting a promising therapeutic approach against OAT.
Topics: Rats; Male; Animals; Humans; Heme Oxygenase-1; Rats, Sprague-Dawley; NF-E2-Related Factor 2; Tripterygium; Oligospermia; Glycosides; Moxibustion; Asthenozoospermia; Infertility, Male; Seeds; Oxidative Stress; Antioxidants; Signal Transduction; Superoxide Dismutase; RNA, Messenger
PubMed: 38277193
DOI: 10.18632/aging.205475 -
Journal of Assisted Reproduction and... Mar 2024To investigate the prevalence of Y chromosome polymorphisms in Chinese men and analyze their associations with male infertility and female adverse pregnancy outcomes.
PURPOSE
To investigate the prevalence of Y chromosome polymorphisms in Chinese men and analyze their associations with male infertility and female adverse pregnancy outcomes.
METHODS
The clinical data of 32,055 Chinese men who underwent karyotype analysis from October 2014 to September 2019 were collected. Fisher's exact test, chi-square test, or Kruskal-Wallis test was used to analyze the effects of Y chromosome polymorphism on semen parameters, azoospermia factor (AZF) microdeletions, and female adverse pregnancy outcomes.
RESULTS
The incidence of Y chromosome polymorphic variants was 1.19% (381/32,055) in Chinese men. The incidence of non-obstructive azoospermia (NOA) was significantly higher in men with the Yqh- variant than that in men with normal karyotype and other Y chromosome polymorphic variants (p < 0.050). The incidence of AZF microdeletions was significantly different among the normal karyotype and different Y chromosome polymorphic variant groups (p < 0.001). The detection rate of AZF microdeletions was 28.92% (24/83) in the Yqh- group and 2.50% (3/120) in the Y ≤ 21 group. The AZFb + c region was the most common AZF microdeletion (78.57%, 22/28), followed by AZFc microdeletion (7.14%,2/28) in NOA patients with Yqh- variants. There was no significant difference in the distribution of female adverse pregnancy outcomes among the normal karyotype and different Y chromosome polymorphic variant groups (p = 0.528).
CONCLUSIONS
Patients with 46,XYqh- variant have a higher incidence of NOA and AZF microdeletions than patients with normal karyotype and other Y chromosome polymorphic variants. Y chromosome polymorphic variants do not affect female adverse pregnancy outcomes.
Topics: Humans; Male; Female; Azoospermia; Retrospective Studies; Chromosome Deletion; Infertility, Male; Chromosomes, Human, Y; China; Oligospermia
PubMed: 38270748
DOI: 10.1007/s10815-024-03022-y -
Journal of Pediatric Urology Jun 2024With advances in medical care and assisted reproductive technologies (ART), fertility prospects for prune-belly syndrome (PBS) men may be changing. This review aims to... (Review)
Review
INTRODUCTION
With advances in medical care and assisted reproductive technologies (ART), fertility prospects for prune-belly syndrome (PBS) men may be changing. This review aims to identify the factors influencing fertility and optimization of reproductive health for PBS patients.
MATERIAL AND METHODS
A scoping review was performed on all records published over 70 years (1952-2022) analyzing fertility in PBS males. Records were summarized in a table and narrative describing cryptorchidism, orchiopexy, testicle histology; prostate characteristics; sex hormone function; semen analyses, ART, and conception ability. This review was registered on Open Science Framework (OSF) and conducted using PRISMA methodology.
RESULTS
827 articles were identified and 83 were selected for data extraction. Before 2000, there were 0.85 publications/year whereas after 2000 there were 1.95 publications/year. Orchiopexy successfully relocated 86 % of PBS testicles into the scrotum. Testicular histology demonstrated 50 % of patients had no spermatogonia, while 47.2 % and 2.7 % had reduced or normal numbers respectively. Leydig hyperplasia and Sertoli only histology were found in 19.4 % of patients. Prostatic hypoplasia and prostatic urethral dilation were found in 93.6 % and 91.4 % of patients respectively. Testosterone, Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) were normal in 93.9 %, 87.7 % and 77.9 % of patients respectively. Azoospermia and oligospermia was found in 75.7 % and 21.6 % of patients respectively while 60.7 % had antegrade ejaculation. ART successfully extracted sperm in 6 instances and resulted in 4 conceptions, while natural conception was reported twice.
CONCLUSIONS
Data analysis indicates increased attention to fertility prospects for PBS males with evaluation of PBS patient's hormonal function, semen analyses, ART, and conception ability. The reviewed data suggest that PBS males may father biological offspring with contemporary management and also demonstrate the need for consistent reproductive management approaches to maximize their fertility prospects.
Topics: Humans; Male; Fertility; Prune Belly Syndrome; Infertility, Male; Orchiopexy; Reproductive Techniques, Assisted
PubMed: 38267308
DOI: 10.1016/j.jpurol.2024.01.005 -
Urology Journal Jun 2024This review presents a clinical approach to genetic issues in male infertility. Unlike other related reviews that discuss different types of genetic diseases (such as... (Review)
Review
PURPOSE
This review presents a clinical approach to genetic issues in male infertility. Unlike other related reviews that discuss different types of genetic diseases (such as Klinefelter and Down syndrome), this review focuses on the clinical features that result from these genetic problems (such as azoospermia and oligospermia).
METHODS
A narrative review of the clinical literature in PubMed was conducted using keywords related to male infertility, recurrent pregnancy loss, recurrent in vitro fertilization failure, and genetics. The search included articles with English reviews published online after 2020. Headlines were defined based on the available literature, and after a critical review of each manuscript, clinical facts were classified under the corresponding headlines, and a primary draft was written.
RESULTS
29 relevant articles were selected from the search. According to the literature, there are clinical genetic approaches for azoospermia, severe oligospermia, severe teratospermia, severe asthenospermia, recurrent miscarriage, and recurrent in vitro fertilization failure.
CONCLUSION
Although many mutations that can affect male fertility and spermogram have been identified, only a few have clinical predictive value.
Topics: Humans; Male; Abortion, Habitual; Infertility, Male; Female; Fertilization in Vitro; Pregnancy; Genetic Testing; Azoospermia; Oligospermia; Treatment Failure
PubMed: 38264866
DOI: 10.22037/uj.v20i.8044 -
Molecular Human Reproduction Feb 2024Oligozoospermia and azoospermia are two common phenotypes of male infertility characterized by massive sperm defects owing to failure of spermatogenesis. The deleterious...
Oligozoospermia and azoospermia are two common phenotypes of male infertility characterized by massive sperm defects owing to failure of spermatogenesis. The deleterious impact of candidate variants with male infertility is to be explored. In our study, we identified three hemizygous missense variants (c.388G>A: p.V130M, c.272C>T: p.A91V, and c.467C>T: p.A156V) and one hemizygous nonsense variant (c.478C>T: p.R160X) in the Rhox homeobox family member 1 gene (RHOXF1) in four unrelated cases from a cohort of 1201 infertile Chinese men with oligo- and azoospermia using whole-exome sequencing and Sanger sequencing. RHOXF1 was absent in the testicular biopsy of one patient (c.388G>A: p.V130M) whose histological analysis showed a phenotype of Sertoli cell-only syndrome. In vitro experiments indicated that RHOXF1 mutations significantly reduced the content of RHOXF1 protein in HEK293T cells. Specifically, the p.V130M, p.A156V, and p.R160X mutants of RHOXF1 also led to increased RHOXF1 accumulation in cytoplasmic particles. Luciferase assays revealed that p.V130M and p.R160X mutants may disrupt downstream spermatogenesis by perturbing the regulation of doublesex and mab-3 related transcription factor 1 (DMRT1) promoter activity. Furthermore, ICSI treatment could be beneficial in the context of oligozoospermia caused by RHOXF1 mutations. In conclusion, our findings collectively identified mutated RHOXF1 to be a disease-causing X-linked gene in human oligo- and azoospermia.
Topics: Humans; Male; Azoospermia; Genes, X-Linked; HEK293 Cells; Infertility, Male; Oligospermia; Semen
PubMed: 38258527
DOI: 10.1093/molehr/gaae002 -
International Journal of Molecular... Jan 2024Infertility affects millions of couples worldwide and has a profound impact not only on their families, but also on communities. Telomere attrition has been associated...
Infertility affects millions of couples worldwide and has a profound impact not only on their families, but also on communities. Telomere attrition has been associated with infertility, DNA damage and fragmentation. Oxidative stress has been shown to affect sperm DNA integrity and telomere length. Sirtuins such as SIRT1 and SIRT3 are involved in aging and oxidative stress response. The aim of the present study is to determine the role of SIRT1 and SIRT3 in regulating oxidative stress, telomere shortening, and their association with oligospermia. Therefore, we assessed the protein levels of SIRT1 and SIRT3, total antioxidant capacity (TAC), superoxide dismutase (SOD), malondialdehyde (MDA) and catalase activity (CAT) in the seminal plasma of 272 patients with oligospermia and 251 fertile men. We also measured sperm telomere length (STL) and leukocyte telomere length (LTL) using a standard real-time quantitative PCR assay. Sperm chromatin and protamine deficiency were also measured as per standard methods. Our results for oligospermic patients demonstrate significant reductions in semen parameters, shorter STL and LTL, lower levels of SOD, TAC, CAT, SIRT1 and SIRT3 levels, and also significant protamine deficiency and higher levels of MDA and DNA fragmentation. We conclude that a shorter TL in sperms and leukocytes is associated with increased oxidative stress that also accounts for high levels of DNA fragmentation in sperms. Our results support the hypothesis that various sperm parameters in the state of oligospermia are associated with or caused by reduced levels of SIRT1 and SIRT3 proteins.
Topics: Humans; Male; Semen; Oligospermia; Antioxidants; Sirtuin 3; Sirtuin 1; Spermatozoa; Protamines; Superoxide Dismutase
PubMed: 38255792
DOI: 10.3390/ijms25020718 -
Archives of Razi Institute Aug 2023Open testicular biopsy histology and fine needle aspiration cytology (FNAC) are the most popular tests used to diagnose male infertility. This study aimed to assess the...
A Comparative Investigation Applying Testicular Fine Needle Aspiration Cytology and Open Testicular Biopsy Histology for the Diagnosis of Azoospermia and Severe Oligospermia.
Open testicular biopsy histology and fine needle aspiration cytology (FNAC) are the most popular tests used to diagnose male infertility. This study aimed to assess the cytological characteristics of 186 infertile males aged 24-63 with testicular FNAC. Furthermore, the existing relationship between males with severe oligospermia (sperm count: 5 million/ml) and azoospermia was investigated via both cytological and histological diagnosis methods. With a 1.5-inch and 25-gauge needle, the testis was aspirated from three locations (the upper, middle, and lower poles). Papanicolaou stain or Giemsa stain was used to make smears on albumenized slides, which were then dried in the air and stained. A biopsy of the testicles was performed there, preserved in Bouins solution, processed as usual, and stained with hematoxylin and eosin stain. According to our findings, 66.7% of patients had secondary maturation arrest, whereas 18.3% and 15.1% of them had hypospermatogenesis and Sertoli cell only (SCO). Results of the comparison showed that both procedures were very similar. According to biopsy histological examinations, only 3 (1.6%) of the 28 normal FNAC instances had hypospermatogenesis with lymphocyte infiltration. The majority of SCO patients were over 50 years old. These findings revealed that FNAC is more effective than testicular histology for the assessment of male infertility.
Topics: Male; Humans; Middle Aged; Testis; Biopsy, Fine-Needle; Oligospermia; Azoospermia; Semen; Infertility, Male
PubMed: 38226384
DOI: 10.32592/ARI.2023.78.4.1343 -
Human Reproduction (Oxford, England) Mar 2024Genetic causes account for 10-15% of male factor infertility, making the genetic investigation an essential and useful tool, mainly in azoospermic and severely...
Genetic causes account for 10-15% of male factor infertility, making the genetic investigation an essential and useful tool, mainly in azoospermic and severely oligozoospermic men. In these patients, the most frequent findings are chromosomal abnormalities and Y chromosome long arm microdeletions, which cause a primary severe spermatogenic impairment with classically increased levels of FSH. On the other hand, polymorphisms in the FSH receptor (FSHR) and FSH beta chain (FSHB) genes have been associated with different FSH plasma levels, due to variations in the receptor sensitivity (FSHR) or in the production of FSH from the pituitary gland (FSHB). Here, we describe an unusual patient with a combined genetic alteration (classic AZFc deletion of the Y chromosome and TT homozygosity for the -211G>T polymorphism in the FSHB gene (rs10835638)), presenting with cryptozoospermia, severe hypospermatogenesis, and normal LH and testosterone plasma concentrations, but low FSH levels. The patient partially benefitted from treatment with FSH (150 IU three times/week for 6 months) which allowed him to cryopreserve enough motile spermatozoa to be used for intracytoplasmic sperm injection. According to our knowledge, this is the first report of an infertile man with AZFc microdeletion with low FSH plasma concentrations related to homozygosity for the -211G>T polymorphism in the FSHB gene.
Topics: Humans; Male; Polymorphism, Single Nucleotide; Semen; Infertility, Male; Follicle Stimulating Hormone, beta Subunit; Oligospermia; Chromosomes, Human, Y; Chromosome Deletion; Sex Chromosome Aberrations; Sex Chromosome Disorders of Sex Development
PubMed: 38224259
DOI: 10.1093/humrep/dead277 -
Chemico-biological Interactions Feb 2024Busulfan, a bifunctional alkylated chemotherapeutic agent, has male reproductive toxicity and induce oligospermia, which is associated with ferroptosis. However, the...
Busulfan, a bifunctional alkylated chemotherapeutic agent, has male reproductive toxicity and induce oligospermia, which is associated with ferroptosis. However, the specific target cells of busulfan-induced oligospermia triggered by ferroptosis are largely elusive, and the detailed mechanisms also require further exploration. In the present study, busulfan (0.6, and 1.2 mM, 48 h) causes ferroptosis in GC-1 spg cells through inducing Fe, ROS and MDA accumulation and functional inhibition of Xc-GSH-GPX4 antioxidant system. After inhibition of ferroptosis by Fer-1 (1 μM, pretreatment for 2 h) or DFO (10 μM, pretreatment for 2 h) reverses busulfan-induced destructive effects in GC-1 spg cells. Furthermore, using RNA-seq and Western blotting, we found that busulfan promotes autophagy-dependent ferritin degradation, as reflected by enriching in autophagy, increased LC3 II, Beclin1 and NCOA4, as well as decreased P62 and ferritin heavy chain 1 (FTH1). Ultimately, GC-1 spg cells and Balb/c mice were treated with busulfan and/or 3-MA, the inhibitor of autophagy. The results displayed that inhibition of autophagy relieves busulfan-induced FTH1 degradation and then blocks the occurrence of ferroptosis in GC-1 spg cells and testicular spermatogonia, which subsequently alleviates busulfan-caused testicular damage and spermatogenesis disorders. In summary, these data collectively indicated that ferroptosis of spermatogonia is involved in busulfan-induced oligospermia and mediated by autophagy-dependent FTH1 degradation, identifying a new target for the therapy of busulfan-induced male infertility.
Topics: Humans; Male; Animals; Mice; Busulfan; Spermatogonia; Oligospermia; Ferroptosis; Autophagy; Acetates; Phenols
PubMed: 38220133
DOI: 10.1016/j.cbi.2024.110870 -
Reproductive Sciences (Thousand Oaks,... Jun 2024Oligo-astheno-teratozoospermia (OAT), which is a common cause of male infertility, can be caused by genetic factors. This study reports on a case of a male patient...
Oligo-astheno-teratozoospermia (OAT), which is a common cause of male infertility, can be caused by genetic factors. This study reports on a case of a male patient suffering from infertility concomitant with OAT. Whole-exome sequencing (WES) confirmed the presence of a homozygous variant (NM_003462: c.464-1G > A) in the DNALI1 gene via Sanger sequencing. Immunofluorescence staining demonstrated that the DNALI1 signal was nearly undetectable in the patient's sperm. Bioinformatics analysis revealed that this mutation could reverse the splicing of the exon 4 acceptor splice site. A minigene experiment was performed to verify the mutation and the results confirmed that the mutation disrupted the splicing. Our findings show that this rare mutation in DNALI1 contributes to male infertility and OAT in humans, thereby expanding our understanding of the causes and pathogenesis of male infertility. This knowledge facilitates genetic counseling, clinical diagnosis, and therapeutic development of male infertility.
Topics: Humans; Male; Infertility, Male; Mutation; Asthenozoospermia; Oligospermia; Adult; Teratozoospermia; RNA Splicing; Exome Sequencing
PubMed: 38212584
DOI: 10.1007/s43032-023-01451-1