-
Urologia Nov 2023Most genitourinary tract cancers have a negative impact on male fertility. Although testicular cancers have the worst impact, other tumors such as prostate, bladder, and... (Review)
Review
Most genitourinary tract cancers have a negative impact on male fertility. Although testicular cancers have the worst impact, other tumors such as prostate, bladder, and penis are diagnosed early and treated in relatively younger patients in which couple fertility can be an important concern. The purpose of this review is to highlight both the pathogenetic mechanisms of damage to male fertility in the context of the main urological cancers and the methods of preserving male fertility in an oncological setting, in light of the most recent scientific evidence. A systematic review of available literature was carried out on the main scientific search engines, such as PubMed, Clinicaltrials.Gov, and Google scholar. Three hundred twenty-five relevant articles on this subject were identified, 98 of which were selected being the most relevant to the purpose of this review. There is a strong evidence in literature that all of the genitourinary oncological therapies have a deep negative impact on male fertility: orchiectomy, partial orchiectomy, retroperitoneal lymphadenectomy (RPLND), radical cystectomy, prostatectomy, penectomy, as well as radiotherapy, chemotherapy, and hormonal androgen suppression. Preservation of fertility is possible and includes cryopreservation, hormonal manipulation with GnRH analogs before chemotherapy, androgen replacement. Germ cell auto transplantation is an intriguing strategy with future perspectives. Careful evaluation of male fertility must be a key point before treating genitourinary tumors, taking into account patients' age and couples' perspectives. Informed consent should provide adequate information to the patient about the current state of his fertility and about the balance between risks and benefits in oncological terms. Standard approaches to genitourinary tumors should include a multidisciplinary team with urologists, oncologists, radiotherapists, psycho-sexologists, andrologists, gynecologists, and reproductive endocrinologists.
Topics: Humans; Male; Fertility Preservation; Androgens; Infertility, Male; Testicular Neoplasms; Urologic Neoplasms
PubMed: 37491831
DOI: 10.1177/03915603221146147 -
Frontiers in Endocrinology 2023Steroidogenic factor 1 (SF-1), encoded by the nuclear receptor subfamily 5 group A member 1 () gene, is a transcriptional factor crucial for adrenal and gonadal...
BACKGROUND
Steroidogenic factor 1 (SF-1), encoded by the nuclear receptor subfamily 5 group A member 1 () gene, is a transcriptional factor crucial for adrenal and gonadal organogenesis. Pathogenic variants of are responsible for a wide spectrum of phenotypes with autosomal dominant inheritance including disorders of sex development and oligospermia-azoospermia in 46,XY adults. Preservation of fertility remains challenging in these patients.
OBJECTIVE
The aim was to offer fertility preservation at the end of puberty in an mutated patient.
CASE REPORT
The patient was born of non-consanguineous parents, with a disorder of sex development, a small genital bud, perineal hypospadias, and gonads in the left labioscrotal fold and the right inguinal region. Neither uterus nor vagina was detected. The karyotype was 46,XY. Anti-Müllerian hormone (AMH) and testosterone levels were low, indicating testicular dysgenesis. The child was raised as a boy. At 9 years old, he presented with precocious puberty treated by triptorelin. At puberty, follicle-stimulating hormone (FSH), luteinising hormone (LH), and testosterone levels increased, whereas AMH, inhibin B, and testicular volume were low, suggesting an impaired Sertoli cell function and a partially preserved Leydig cell function. A genetic study performed at almost 15 years old identified the new frameshift variant NM_004959.5: c.207del p.(Phe70Ser*5) at a heterozygous state. He was thus addressed for fertility preservation. No sperm cells could be retrieved from three semen collections between the ages of 16 years 4 months and 16 years 10 months. A conventional bilateral testicular biopsy and testicular sperm extraction were performed at 17 years 10 months of age, but no sperm cells were found. Histological analysis revealed an aspect of mosaicism with seminiferous tubules that were either atrophic, with Sertoli cells only, or presenting an arrest of spermatogenesis at the spermatocyte stage.
CONCLUSION
We report a case with a new variant. The fertility preservation protocol proposed at the end of puberty did not allow any sperm retrieval for future parenthood.
Topics: Male; Anti-Mullerian Hormone; Follow-Up Studies; Sexual Maturation; Steroidogenic Factor 1; Testis; Testosterone; Humans; Child; Adolescent
PubMed: 37409232
DOI: 10.3389/fendo.2023.1171822 -
Experimental and Therapeutic Medicine Jul 2023The present study aimed to investigate the occurrence of chromosomal karyotype abnormalities and azoospermia factor () microdeletion on the long arm of the Y chromosome...
The present study aimed to investigate the occurrence of chromosomal karyotype abnormalities and azoospermia factor () microdeletion on the long arm of the Y chromosome (Yq) in infertile men, and to determine their association with infertility to ultimately improve clinical outcomes in these patients. A total of 1,980 azoospermic and oligospermic men from the outpatient department of the Fujian Maternity and Child Health Hospital (Fuzhou, China) were recruited between January 2016 and December 2019. Peripheral blood was used for karyotype analysis; microdeletion analysis of the Yq was performed using capillary electrophoresis. Among the 1,980 patients, 178 had chromosomal abnormalities (9.0%; 178/1,980), of whom 98 had an abnormal number of chromosomes. Among the abnormal karyotypes, the most common was 47, XXY (80/178; 44.9%). microdeletion on the Yq occurred at a rate of 10.66% (211/1,980); the most common type was the deletion (sY1192; 140/211; 66.4%). The present findings showed that karyotype abnormalities and gene microdeletion are important drivers of male infertility. Specifically, men with Yqh- and del(Y)(q11) had a higher risk of microdeletion. These results suggested that patient treatment could be personalized based on routine molecular genetic analysis, which could further alleviate the economic and emotional burden of undergoing redundant or ineffective treatments.
PubMed: 37383371
DOI: 10.3892/etm.2023.12044 -
The World Journal of Men's Health Jan 2024Male overweight and obesity could affect sperm quality and reproductive health. However, the impact of body mass index (BMI) on assisted reproductive technology (ART)...
PURPOSE
Male overweight and obesity could affect sperm quality and reproductive health. However, the impact of body mass index (BMI) on assisted reproductive technology (ART) outcomes in oligospermia and/or asthenospermia patients is yet lacking. This study aims to assess the impact of paternal BMI on ART and neonatal outcomes among oligozoospermia and/or asthenospermia patients undergoing fertilization (IVF)/intracytoplasmic sperm injection (ICSI).
MATERIALS AND METHODS
In this study, 2,075 couples undergoing their first fresh embryo transfer between January 2015 and June 2022 were recruited. Following the World Health Organization's (WHO's) categories, couples were stratified into three cohorts based on paternal BMI: normal weight (18.5-24.9 kg/m²), overweight (25.0-29.9 kg/m²), and obese (≥30.0 kg/m²). Modified Poisson regression models were used to assess the associations of paternal BMI with fertilization, embryonic development, and pregnancy outcomes. Logistic regression models were performed to investigate the associations of paternal BMI with pregnancy loss and neonatal outcomes. Furthermore, stratified analyses were performed based on fertilization methods, male infertility cause, and maternal BMI.
RESULTS
Higher paternal BMI is associated with a lower likelihood of achieving normal fertilized (p-trend=0.002), Day 3 transferable (p-trend=0.007), and high-quality embryos (p-trend=0.046) in IVF cycles, rather than in ICSI cycles. Paternal BMI of oligospermia or asthenospermia was negatively correlated with day 3 transferable (p-trend=0.013 and 0.030) and high-quality embryos (p-trend=0.024 and 0.027). Moreover, for neonatal outcomes, paternal BMI was positively associated with macrosomia (p-trend=0.019), large for gestational age (LGA) (p-trend=0.031), and very LGA (p-trend=0.045).
CONCLUSIONS
Our data suggested that higher paternal BMI was associated with fetal overgrowth, reduced fertilization, and embryonic development potential. Among males with oligospermia and/or asthenospermia, the impact of overweight and obesity on the choice of fertilization method and the long-term effects on their offspring need to be further investigated.
PubMed: 37382283
DOI: 10.5534/wjmh.220286 -
Frontiers in Microbiology 2023Semen quality is decreasing worldwide, leading to increased male infertility. This study analyzed the microbiota of the gut, semen, and urine in individuals with semen...
INTRODUCTION
Semen quality is decreasing worldwide, leading to increased male infertility. This study analyzed the microbiota of the gut, semen, and urine in individuals with semen abnormalities to identify potential probiotics and pathogenic bacteria that affect semen parameters and help develop new methods for the diagnosis and treatment of patients with semen abnormalities.
METHODS
We recruited 12 individuals with normal semen parameters (control group), 12 with asthenospermia but no semen hyperviscosity (Group_1), 6 with oligospermia (Group_2), 9 with severe oligospermia or azoospermia (Group_3), and 14 with semen hyperviscosity only (Group_4). The semen, gut, and urine microbiota were examined by analyzing the 16S ribosomal RNA gene sequence using next-generation sequencing.
RESULTS
The gut microbes were clustered into the highest number of operational taxonomic units, followed by urine and semen. Furthermore, the α-diversity of gut microbes was highest and significantly different from that of urine and semen microbiota. The microbiota of the gut, urine, and semen were all significantly different from each other in terms of β-diversity. The gut abundance of was significantly reduced in groups 1, 3, and 4. Furthermore, the gut abundance of and was significantly decreased in Group_1, while that of was significantly increased in Group_3. The abundance of was significantly increased in the semen of groups 1 and 4. Finally, abundance was significantly reduced in the urine of groups 2 and 4.
DISCUSSION
This study comprehensively describes the differences in intestinal and genitourinary tract microbiota between healthy individuals and those with abnormal semen parameters. Furthermore, our study identified , , , and as potential probiotics. Finally, the study identified in the gut and in semen as potential pathogenic bacteria. Our study lays the foundation of a new approach to the diagnosis and treatment of male infertility.
PubMed: 37293215
DOI: 10.3389/fmicb.2023.1182320 -
Asian Journal of Andrology Nov 2023
Topics: Male; Humans; Avena; Infertility, Male; Oligospermia; Asthenozoospermia; Spermatozoa
PubMed: 37282384
DOI: 10.4103/aja202322 -
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 -
Reproductive Sciences (Thousand Oaks,... Oct 2023The present study compared seminal calbindin 2 (CALB 2) levels and semen parameters in men with and without varicocele. CALB 2 is also known as calretinin and 29 kDa...
The present study compared seminal calbindin 2 (CALB 2) levels and semen parameters in men with and without varicocele. CALB 2 is also known as calretinin and 29 kDa calbindin. The study was a case-control study conducted from April (2021) to March (2022) in the andrology department at Beni-Suef University hospital. The study included four matched groups: group (I) were controls (fertile normozoospermic men without varicocele) (n=24). Group (II) were fertile normozoospermic men with varicocele (n=24). Group (III) were infertile oligoasthenoteratozoospermia (OAT) men without varicocele (n=24). Group (IV) were infertile OAT men with varicocele (n=24). The lowest levels of seminal CALB 2 were found in patients with severe oligozoospermia which showed a statistically significant difference when compared to seminal CALB 2 in patients with normal, mildly low, or moderately low sperm counts. There were significant negative correlations between sperm concentration, sperm motility and percentage of normal sperm forms and seminal CALB 2. Seminal plasma CALB 2 may play a role in the negative impact of varicocele on the semen parameters especially sperm concentration, sperm motility and percentage of sperm normal forms. Future studies are needed to verify these findings.
Topics: Humans; Male; Infertility, Male; Calbindin 2; Semen; Varicocele; Prospective Studies; Case-Control Studies; Sperm Motility; Oligospermia; Sperm Count
PubMed: 37067726
DOI: 10.1007/s43032-023-01237-5 -
Journal of Lasers in Medical Sciences 2022About 50% of infertility problems are related to male factors and reduced sperm motility. The important factor that affects the structure and function of sperm is... (Review)
Review
About 50% of infertility problems are related to male factors and reduced sperm motility. The important factor that affects the structure and function of sperm is reactive oxygen species (ROS), and over-concentration of ROS reduces the quality and motility of sperm. Photobiomodulation therapy (PBMT) using red to near-infrared (NIR) light is useful in oxidative stress restoration. It plays a therapeutic role in disorders such as asthenospermia, oligospermia cases, and cryopreserved sperm. It also enhances the metabolic capacity of sperm and increases the low-level and non-harmful intracellular content of Ca, nitric oxide (NO), and ROS in the stressed cells. Likewise, it modulates survival intracellular pathways and maintains the motility, viability, DNA, and acrosome integrity of sperm. This article reviews the state-of-the-art preclinical and clinical evidence regarding the efficacy of semen PBMT.
PubMed: 37041786
DOI: 10.34172/jlms.2022.75 -
Communications Biology Apr 2023Long-form collapsin response mediator protein-1 (LCRMP-1) belongs to the CRMP family which comprises brain-enriched proteins responsible for axon guidance. However, its...
Long-form collapsin response mediator protein-1 (LCRMP-1) belongs to the CRMP family which comprises brain-enriched proteins responsible for axon guidance. However, its role in spermatogenesis remains unclear. Here we find that LCRMP-1 is abundantly expressed in the testis. To characterize its physiological function, we generate LCRMP-1-deficient mice (Lcrmp-1). These mice exhibit aberrant spermiation with apoptotic spermatids, oligospermia, and accumulation of immature testicular cells, contributing to reduced fertility. In the seminiferous epithelial cycle, LCRMP-1 expression pattern varies in a stage-dependent manner. LCRMP-1 is highly expressed in spermatids during spermatogenesis and especially localized to the spermiation machinery during spermiation. Mechanistically, LCRMP-1 deficiency causes disorganized F-actin due to unbalanced signaling of F-actin dynamics through upregulated PI3K-Akt-mTOR signaling. In conclusion, LCRMP-1 maintains spermatogenesis homeostasis by modulating cytoskeleton remodeling for spermatozoa release.
Topics: Animals; Male; Mice; Actins; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Spermatids; Spermatogenesis; Nerve Tissue Proteins
PubMed: 37037996
DOI: 10.1038/s42003-023-04778-2