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Genetics in Medicine : Official Journal... Dec 2020Male infertility remains poorly understood at the molecular level. We aimed in this study to investigate the yield of a "genomics first" approach to male infertility.
PURPOSE
Male infertility remains poorly understood at the molecular level. We aimed in this study to investigate the yield of a "genomics first" approach to male infertility.
METHODS
Patients with severe oligospermia and nonobstructive azoospermia were investigated using exome sequencing (ES) in parallel with the standard practice of chromosomal analysis.
RESULTS
In 285 patients, 10.5% (n = 30) had evidence of chromosomal aberrations while nearly a quarter (n = 69; 24.2%) had a potential monogenic form of male infertility. The latter ranged from variants in genes previously reported to cause male infertility with or without other phenotypes in humans (24 patients; 8.4%) to those in novel candidate genes reported in this study (37 patients; 12.9%). The 33 candidate genes have biological links to male germ cell development including compatible mouse knockouts, and a few (TERB1 [CCDC79], PIWIL2, MAGEE2, and ZSWIM7) were found to be independently mutated in unrelated patients in our cohort. We also found that male infertility can be the sole or major phenotypic expression of a number of genes that are known to cause multisystemic manifestations in humans (n = 9 patients; 3.1%).
CONCLUSION
The standard approach to male infertility overlooks the significant contribution of monogenic causes to this important clinical entity.
Topics: Animals; Argonaute Proteins; Carrier Proteins; Cell Cycle Proteins; Chromosome Deletion; Chromosomes, Human, Y; Genomics; Humans; Infertility, Male; Male; Mice; Oligospermia; Sex Chromosome Aberrations
PubMed: 32719396
DOI: 10.1038/s41436-020-0916-0 -
Zhonghua Nan Ke Xue = National Journal... May 2018Sperm cryopreservation has been widely used in assisted reproduction, but conventional techniques are not suitable for the cryopreservation of small numbers of sperm.... (Review)
Review
Sperm cryopreservation has been widely used in assisted reproduction, but conventional techniques are not suitable for the cryopreservation of small numbers of sperm. The application of the single sperm cryopreservation technique has significantly improved the clinical treatment of cryptozoospermia and non-obstructive azoospermia. Ever since Cohen et al first developed the method of single sperm cryopreservation in 1997, constant efforts have been made to develop the carriers for this technique. In this review, we mainly discuss the existing methods and clinical outcomes of single sperm cryopreservation.
Topics: Azoospermia; Cryopreservation; Heterozygote; Humans; Male; Oligospermia; Reproduction; Semen Preservation; Spermatozoa
PubMed: 30171762
DOI: No ID Found -
Best Practice & Research. Clinical... Feb 2019Advances in the treatment of cancer in young patients have led to great improvements in life expectancy, which currently approaches 80% 5-year survival rate. As a... (Review)
Review
Advances in the treatment of cancer in young patients have led to great improvements in life expectancy, which currently approaches 80% 5-year survival rate. As a result, fertility preservation and desire for paternity have become a significant issue in this group. However, a major concern is the negative impact of chemotherapy, radiotherapy, and the malignancy itself on fertility. Thus, men about to have treatment for malignant conditions may have sperm cryopreserved before commencing chemotherapy or radiotherapy. Ejaculated sperm cryopreservation is the most common technique used. Some patients with cancer may present initially with oligospermia or azoospermia. In cases when a sample is not produced due to medical, social, or religious reasons, sperm can be retrieved using penile vibratory stimulation, electroejaculation, or testicular sperm extraction. Fertility preservation in prepubertal boys presents a great challenge, as sperm banking is not possible. Alternative strategies have been developed, but all are currently experimental.
Topics: Azoospermia; Cryopreservation; Fertility Preservation; Humans; Infertility, Male; Male; Neoplasms; Oligospermia; Spermatozoa
PubMed: 30744950
DOI: 10.1016/j.bpobgyn.2018.12.004 -
The Journal of Biological Chemistry Jun 2023N6-methyladenosine (m6A) is the most prevalent reversible RNA modification in the mammalian transcriptome. It has recently been demonstrated that m6A is crucial for male...
N6-methyladenosine (m6A) is the most prevalent reversible RNA modification in the mammalian transcriptome. It has recently been demonstrated that m6A is crucial for male germline development. Fat mass and obesity-associated factor (FTO), a known m6A demethylase, is widely expressed in human and mouse tissues and is involved in manifold biological processes and human diseases. However, the function of FTO in spermatogenesis and male fertility remains poorly understood. Here, we generated an Fto knockout mouse model using CRISPR/Cas9-mediated genome editing techniques to address this knowledge gap. Remarkably, we found that loss of Fto in mice caused spermatogenesis defects in an age-dependent manner, resulting from the attenuated proliferation ability of undifferentiated spermatogonia and increased male germ cell apoptosis. Further research showed that FTO plays a vital role in the modulation of spermatogenesis and Leydig cell maturation by regulating the translation of the androgen receptor in an m6A-dependent manner. In addition, we identified two functional mutations of FTO in male infertility patients, resulting in truncated FTO protein and increased m6A modification in vitro. Our results highlight the crucial effects of FTO on spermatogonia and Leydig cells for the long-term maintenance of spermatogenesis and expand our understanding of the function of m6A in male fertility.
Topics: Animals; Humans; Male; Mice; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Cell Differentiation; Mutation; Spermatogenesis; Age Factors; Female; Fertility; Gene Deletion; Oligospermia
PubMed: 37146971
DOI: 10.1016/j.jbc.2023.104783 -
Fertility and Sterility Feb 2021
Topics: Azoospermia; Humans; Male; Oligospermia; Sperm Injections, Intracytoplasmic
PubMed: 33039129
DOI: 10.1016/j.fertnstert.2020.09.130 -
Sensors (Basel, Switzerland) Feb 2023(kinetochore scaffold 1) has attracted much attention as one of the assembly elements of the outer kinetochore, and the functions of its different domains have been...
The Loss-Function of Causes Oligospermia and Asthenospermia in Mice by Affecting the Assembly and Separation of the Spindle through Flow Cytometry and Immunofluorescence.
(kinetochore scaffold 1) has attracted much attention as one of the assembly elements of the outer kinetochore, and the functions of its different domains have been gradually revealed, most of which are associated with cancers, but few links have been made between and male fertility. Here, we first linked to male reproductive health and the loss-function of resulted in oligospermia and asthenospermia in mice (an 86.5% decrease in total sperm number and an 82.4% increase in static sperm number, respectively) through CASA (computer-aided sperm analysis). Moreover, we introduced an ingenious method to pinpoint the abnormal stage in the spermatogenic cycle using flow cytometry combined with immunofluorescence. Results showed that 49.5% haploid sperm was reduced and 53.2% diploid sperm was increased after the function of was lost. Spermatocytes arrest was identified at the meiotic prophase I of spermatogenesis, which was induced by the abnormal assembly and separation of the spindle. In conclusion, we established an association between and male fertility, providing a guide for future genetic counseling regarding oligospermia and asthenospermia, and a powerful method for further exploring spermatogenic dysfunction by utilizing flow cytometry and immunofluorescence.
Topics: Animals; Male; Mice; Asthenozoospermia; Flow Cytometry; Fluorescent Antibody Technique; Meiosis; Oligospermia; Semen; Microtubule-Associated Proteins
PubMed: 36904774
DOI: 10.3390/s23052571 -
Reproductive Biomedicine Online May 2022The value of assessing subfertile males with oligozoospermia is controversial due to prevailing notions that therapies are limited and ICSI may provide the couple with a...
The value of assessing subfertile males with oligozoospermia is controversial due to prevailing notions that therapies are limited and ICSI may provide the couple with a baby without the need to explain the nature or cause of underlying male infertility. This article highlights that indiscriminately offering ICSI to oligozoospermic men is not free of potential adverse effects and does not grant subfertile men the best fertility pathway. Recent data support associations between oligozoospermia and poor male reproductive health, DNA and epigenetic damage in spermatozoa, and possible adverse health consequences to offspring. Many conditions affecting the testicles are capable of causing oligozoospermia (varicocele, genital infections, congenital and genetic defects testicular torsion/trauma, chronic diseases, inadequate lifestyle, occupational/environmental exposure to toxicants, drugs, cancer and related treatments, acute febrile illness, endocrine disorders, and iatrogenic damage to the genitourinary system). If oligozoospermia is detected, therapeutic interventions can improve sperm quantity/quality and the overall male health, ultimately resulting in better pregnancy outcomes even when ICSI is used. Fertility clinics are urged to engage male infertility specialists in diagnosing and treating oligozoospermia as a matter of best clinical practice. A well-conducted male infertility evaluation represents a unique opportunity to identify relevant medical and infertility conditions, many of which may be treated or alleviated. The andrological assessment may also help guide the optimal application of ICSI. The final goals are to positively impact the overall patient health, the couple's pregnancy prospects, and the offspring's well-being.
Topics: Female; Fertility; Humans; Infertility, Male; Male; Oligospermia; Pregnancy; Sperm Injections, Intracytoplasmic; Spermatozoa
PubMed: 35153142
DOI: 10.1016/j.rbmo.2021.11.026 -
Best Practice & Research. Clinical... Dec 2020Male factor infertility contributes significantly to couples facing difficulty achieving a pregnancy. Genetic factors, and specifically those related to the Y... (Review)
Review
Male factor infertility contributes significantly to couples facing difficulty achieving a pregnancy. Genetic factors, and specifically those related to the Y chromosome, may occur in up to 15% of men with oligozoospermia or azoospermia. A subset of loci within the Y chromosome, known as the azoospermia factors (AZFa, AZFb, and AZFc), have been associated with male infertility. Emerging evidence has demonstrated that microdeletions of at least a subset of these regions may also have impacts on systemic conditions. This review provides a brief review of male infertility and the structure of the Y chromosome, and further highlights the role of Y chromosome microdeletions in male infertility and other systemic disease.
Topics: Azoospermia; Chromosome Deletion; Chromosomes, Human, Y; Female; Humans; Infertility, Male; Male; Oligospermia; Pregnancy; Prognosis; Sex Chromosome Aberrations; Sex Chromosome Disorders of Sex Development
PubMed: 33214080
DOI: 10.1016/j.beem.2020.101471 -
The Canadian Journal of Urology Oct 2017
Topics: Humans; Male; Oligospermia; Sperm Count
PubMed: 28971781
DOI: No ID Found -
Current Pharmaceutical Design 2021Tamoxifen is a selective oestrogen receptor modulator (SERM). SERMs act on oestrogen receptors to inhibit oestradiol mediated negative feedback on the... (Review)
Review
Tamoxifen is a selective oestrogen receptor modulator (SERM). SERMs act on oestrogen receptors to inhibit oestradiol mediated negative feedback on the hypothalamic-pituitary-gonadal (HPG) axis, thereby upregulating gonadotrophin secretion and release from the pituitary. Hence, Tamoxifen is used to upregulate activation of the HPG axis in the treatment of male-factor infertility. However, due to a lack of robust evidence, Tamoxifen has not been FDA approved for use in male-factor infertility and so its use is currently off-label. In this study, we performed a literature search of the OVID medline database and identified 37 studies describing the effects of tamoxifen which we then reviewed. Evidence suggests Tamoxifen effectively increases androgen levels and sperm concentrations in males with idiopathic oligozoospermia. Evidence for increased motility and pregnancy rates in these patients is less conclusive. Further randomised control trials are needed to elucidate the safety of Tamoxifen combination therapies and their efficacy in improving pregnancy rates.
Topics: Estrogens; Female; Humans; Infertility, Male; Male; Oligospermia; Pregnancy; Selective Estrogen Receptor Modulators; Tamoxifen
PubMed: 32053070
DOI: 10.2174/1381612826666200213095228