A novel missense mutation in QRICH2 causes male infertility due to multiple morphological abnormalities of the sperm flagella

Multiple morphological abnormalities of the sperm flagella(MMAF)are characterized by bent,irregular,short,coiled,and absent flagella.MMAF is caused by a variety of genes,some of which have been identified.However,the underlying genetic factors responsible for the majority of MMAF cases are still largely unknown.The glutamine-rich 2(QRICH2)gene plays an essential role in the development of sperm flagella by regulating the expression of essential sperm flagellar biogenesis-associated proteins,and genetic variants of QRICH2 have been identified as the primary cause of MMAF in humans and mice.Here,we recruited a Pakistani consanguineous family to identify the genetic variant causing infertility in patients with MMAF.Whole-exome sequencing and Sanger sequencing were conducted to identify potentially pathogenic variants causing MMAF in infertile patients.Hematoxylin and eosin(HE)staining was performed to analyze sperm morphology.Quantitative polymerase chain reaction,western blot,and immunofluorescence staining analyses were conducted to observe the expression of QRICH2 in spermatozoa.A novel homozygous missense variant(c.4618C>T)in QRICH2 was identified in the affected patients.Morphological analysis of spermatozoa revealed the MMAF phenotype in infertile patients.qPCR revealed a significant reduction in the level of sperm QRICH2 mRNA,and immunofluorescence staining revealed a lack of sperm QRICH2 expression.Additionally,patients harboring a homozygous QRICH2 mutation presented reduced expression of outer dense fiber 2(ODF2)in sperm,whereas sperm expression of A-kinase anchor protein 4(AKAP4)was normal.These findings expand our understanding of the genetic causes of MMAF-associated male infertility and emphasize the importance of genetic counseling.

Epidemiological and Clinical Aspects of Male Infertility in Patients Consulting at the Urology Department of the Yaounde Central Hospital

Introduction: About 10 to 15% of couples in the world and 20 to 30% in Cameroon consult for infertility problems. Infertility is of male origin in 40% of cases. Our objective was to evaluate the epidemiological and clinical aspects of male infertility in our setting. Methods: This was a cross-sectional and descriptive study, with retrospective data collection from the files of patients received for male infertility, over 5 years and 6 months (from January 1st, 2016 to April 30th, 2021) at the Urology Department of the Yaounde Central Hospital. Phone calls were made to patients with incomplete records for completion following a verbal consent. Data reported on data collection forms were entered into a data entry form designed on CSPro software version 7.2. The database was later exported for descriptive statistics using the IBM SPSS software version 23. Qualitative variables were summarized in frequencies and percentages while quantitative variables were summarized in means with their standard deviations for normally distributed data, or medians and interquartile ranges otherwise. Results: Out of 110 patients whose records were analyzed, the median age was 37.0 years, with an interquartile range of 8.3, with 55.5% in the age group 30 to 39 years. Of these 95 (86.4%) were married, 58 (52.7%) were from the West region, 76 (69.1%) were employed. Past history was dominated by mumps 40 (36.4%), varicocele surgery 25 (22.7%), alcoholism 87 (79.1%) and smoking 15 (13.6%). A disorder of spermatogenesis was found in all our patients: 37 (33.6%) azoospermia, 27 (24.6%) asthenospermia and 26 (23.7%) oligospermia patients. Paraclinical evidence of chlamydia and gonococcal infections were found respectively in 38 (34.5%) and 14 (12.7%) patients, varicocele and testicular dystrophy respectively in 95 (86.4%) and 38 (34.5%) patients. Infertility was primary in 67 (60.9%) patients. Conclusion: Most patients with infertility were in their thirties, had risky social habits and comorbidities. An early start of health promotion activities, comorbidities prevention and early detection of spermogram abnormalities would make it possible to reduce the frequency of male infertility.

Spermotrend Improves Semen Quality and Infertility in Men with Varicocele —Spermotrend and Male Infertility

Background: Infertility affects 8% - 12% of couples globally, with approximately half of the cases reported in males. Oxidative stress is a common factor increased in the varicocele condition and particularly affects spermatozoa, due to their sensitivity to oxidative signals and testicular hypotrophy. The objective of this clinical trial is to study the effectiveness of Spermotrend in the improvement of sperm parameters in male infertility. Methods: A total of 170 males aged > 18 years with a diagnosis of infertility and varicocele were consecutively enrolled in a Phase II, open-label clinical trial. Spermotrend was administered 1 capsule (450 mg) orally every 8 hours for 6 months and was evaluated through semen analysis at 4 and 6 months of follow-up. Results: The trial results show a significant improvement following the administration of Spermotrend over 6 months in sperm concentration (44.1% at baseline vs. 64.1% at 6 months), sperm survival (28.2% with sperm survival ≥ 2 hours vs.56.5%), normalization of sperm morphology (31.2% vs. 72.9%). Varicocele condition decreased in all patients and, by the end of the study, 55.3% of patients had normal venous flow and dilation. Only 5.9% of the patients showed grade 2 varicocele at the end of the study, while 38.8% showed grade 1 varicocele, with no patients showing grade 3 varicocele. Regarding testicular hypotrophy, 90.6% of the patients completed the study with normalized testicular volume by recovering normal venous flow. Conclusion: A short-term course of Spermotrend may significantly improve sperm parameters associated with male infertility. Clinical Trial Registration: The clinical trial protocol was registered in the international clinical trial registry, ClinicalTrials.gov, with the code: NCT05222841 on 15/06/2021.

Psychosocial Aspects of Male Infertility at the Service of Urology-Andrology of the Hospital of the Sino-Guinean Friendship

Objective: Describe the psychosocial aspects of male infertility at the hospital of the Sino-Guinean Friendship. Patients and method: It is a prospective study of a descriptive type covering a period of 6 months. The study covered 17 patients, all received for a desire to conceive after at least one year of regular sexual intercourse without contraception. The data were collected from patient interviews using a pre-established questionnaire. Results: The average age of the patients was 32.07 years with extremes of 23 years and 42 years. During this study, 64.70% of patients were no longer participating in community ceremonies. The patients’ relationships with their spouse and family deteriorated in 52.94% and 47.06%, respectively. Conversely, relations with the family of origin remained unchanged in 70.59 percent of cases. The reduction in economic activity was by 13 patients (76.48%). Conclusion: Male infertility causes a real psychic earthquake in men with its corollaries of negative feelings. The rather complex moral repercussions of male infertility affect not only the individual, his/her partner, and family, but also economic activity.

The role of antioxidant therapy in the treatment of male infertility： an overview

In recent years, many studies have focused on the effect of oxidative stress, reactive oxygen species （ROS） and antioxidants on the male eproductive system. Under physiological conditions, sperm produces small amounts of ROS, which are needed for fertilisation, acrosome reaction and capacitation. However, if an increased production of ROS is not associated with a similar increase in scavenging systems, peroxidative damage of the sperm plasma membrane and loss of DNA integrity typically occur, which leads to cell death and reduced fertility. Furthermore, since there is no linear correlation between sperm quality and pregnancy rates, an improvement in semen parameters should not be the sole outcome considered in studies of antioxidant therapies. A definitive conclusion regarding the benefit of these therapies is difficult to obtain, as most of the previous studies lacked control groups, considered different antioxidants in different combinations and doses, or did not evaluate pregnancy rates in previously infertile couples. Even if beneficial effects were reported in a few cases of male infertility, more multicentre, double-blind studies performed with the same criteria are necessarv for an increased understanding of the effects of various antioxidants on fertility,

Antioxidant therapy in male infertility： fact or fiction？

Infertile men have higher levels of semen reactive oxygen species （ROS） than do fertile men. High levels of semen ROS can cause sperm dysfunction, sperm DNA damage and reduced male reproductive potential. This observation has led clinicians to treat infertile men with antioxidant supplements. The purpose of this article is to discuss the rationale for antioxidant therapy in infertile men and to evaluate the data on the efficacy of dietary and in vitro antioxidant preparations on sperm function and DNA damage. To date, most clinical studies suggest that dietary antioxidant supplements are beneficial in terms of improving sperm function and DNA integrity. However, the exact mechanism of action of dietary antioxidants and the optimal dietary supplement have not been established. Moreover, most of the clinical studies are small and few have evaluated pregnancy rates. A beneficial effect of in vitro antioxidant supplements in protecting spermatozoa from exogenous oxidants has been demonstrated in most studies; however, the effect of these antioxidants in protecting sperm from endogenous ROS, gentle sperm processing and cryopreservation has not been established conclusively.

Fertilization of IVF/ICSI Using Sibling Oocytes from Couples with Subfertile Male or Unexplained Infertility

The significance of the performance of conventional in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) using sibling oocytes from couples with subfertile male or unexplained infertility was evaluated. A total of 410 sibling oocyte cumulus-corona complexes (OCCC) from 21 couples with subfertile male (group A) and 11 unexplained infertile couples (group B) were randomly divided, in order of retrieval, into two groups inseminated either by conventional IVF or by ICSI. The treatment outcomes and the influence of infertility factors on fertilization in each group were compared. The results showed that although the two pronuclear (2PN) fertilization rate per injected sibling oocytes was significantly higher after ICSI (group A: 68.2 %±28.8 %; group B: 66.2 %±24.9 %) than after conventional IVF (group A: 41.8 %±32.7 %; group B: 40.1 %±22.1 %), the other variables studied included: the fertilization rates of per allocated sibling oocytes IVF/ICSI, the fertilization rates of sibling oocytes IVF/ICSI after excluding failed IVF fertilization cycles, as well as the cleavage rates of normal fertilization were not statistically significant (P>0.05). Similarly, though the total fertilization failure rate in the IVF group (group A: 42.9 %; group B: 36.4 %) was significantly higher than in the ICSI group (group A: 4.8 %; group B: 0), we did not cancel cycles due to the normal fertilization of sibling oocytes. Embryo transfer was possible in all 32 couples. There were 10 clinical pregnancies in the two groups. We also discovered a possible association between some semen parameters and sperm functions of group A, and women age and duration of infertility of group B and fertilization. It is suggested that adoption of the split IVF/ICSI technology in the above cases may help eliminate fertilization failures. This is also a useful method to investigate the effect of single factor on the employment of assisted reproductive technology.

"Micro-deletions" of the human Y chromosome and their relationship with male infertility

The Y chromosome evolves from an autochromosome and accumulates male-related genes including sex-determining region of Y-chromosome （SRY） and several spermatogenesis-related genes. The human Y chromosome （60 Mb long） is largely composed of repetitive sequences that give it a heterochromatic appearance, and it consists of pseudoautosomal, euchromatic, and heterochromatic regions. Located on the two extremities of the Y chromosome, pseudoautosomal regions 1 and 2 （PAR1 and PAR2, 2.6 Mb and 320 bp long, respectively） are homologs with the termini of the X chromosome. The euchromatic region and some of the repeat-rich heterochromatic parts of the Y chromosome are called ＂male-specific Y＂ （MSY）, which occupy more than 95% of the whole Y chromosome. After evolution, the Y chromosome becomes the smallest in size with the least number of genes but with the most number of copies of genes that are mostly spermatogenesis-related. The Y chromosome is characterized by highly repetitive sequences （including direct repeats, inverted repeats, and palindromes） and high polymorphism. Several gene rearrangements on the Y chromosome occur during evolution owing to its specific gene structure. The consequences of such rearrangements are not only loss but also gain of specific genes. One hundred and fifty three haplotypes have been discovered in the human Y chromosome. The structure of the Y chromosome in the GenBank belongs to haplotype R1. There are 220 genes （104 coding genes, 111 pseudogenes, and 5 other uncategorized genes） according to the most recent count. The 104 coding genes encode a total of about 48 proteins/protein families （including putative proteins/protein families）. Among them, 16 gene products have been discovered in the azoospermia factor region （AZF） and are related to spermatogenesis. It has been discovered that one subset of gene rearrangements on the Y chromosome, ＂micro-deletions＂, is a major cause of male infertility in some populations. However, controversies exist about different Y chromosome haplotypes. Six AZFs of the Y chromosome have been discovered including AZFa, AZFb, AZFc, and their combinations AZFbc, AZFabc, and partial AZFc called AZFc/gr/gr. Different deletions in AZF lead to different content spermatogenesis loss from teratozoospermia to infertility in different populations depending on their Y haplotypes. This article describes the structure of the human Y chromosome and investigates the causes of micro-deletions and their relationship with male infertility from the view of chromosome evolution. After analysis of the relationship between AZFc and male infertility, we concluded that spermatogenesis is controlled by a network of genes, which may locate on the Y chromosome, the autochromosomes, or even on the X chromosome. Further investigation of the molecular mechanisms underlying male fertility/infertility will facilitate our knowledge of functional genomics.

Human protamines and the developing spermatid: their structure, function, expression and relationshipwith male infertility

<abstract>During spermiogenesis, the protamine proteins play an integral role in spermatid chromatin compaction. Recent research has focused on many facets of protamine biology, including protamine gene and protein structure/ function relationships, mechanisms of protamine expression regulation and involvement of the protamines in male fertility. In this paper, we review our current understanding of the structure and function of the protamine-1 (P1) and protamine-2 (P2) proteins and genes, the expression and regulation of these genes and the relationship between the protamines and male fertility. In addition, we offer a brief outlook on future investigation into protamine proteins.

Correlation between HPV sperm infection and male infertility

Human papillomavirus （HPV） is one of the most common sexually transmitted diseases which comprises a group of small DNA viruses that infect both cutaneous and mucous squamous epithelia. Liquid bead microarray technology （LBMA） were used to evaluate 24 HPV genotypes in confirmed fertile and infertile males of North China so that the effects of HPV infection on semen parameters and relationship with male infertility could be discussed. A total of 1138 subjects were recruited in this study; 142 were HPV-positive （12.48%）. Among 523 confirmed fertile males, only 35 were HPV-positive （6.70%）, and two of them had multiple infections. Among 615 infertile males, 107 were HPV-positive （17.4%）, and 29 of them had multiple infections. Infertile males had a relatively high HPV infection rate compared with confirmed fertile males. Sperm progressive motility （PR） and the normal morphology rate were significantly decreased in HPV-positive subjects. HPV-45, HPV-52, HPV-18, HPV-59 and HPV-16 infections were more frequently in infertile males. Hence, HPV infection is closely related to male infertility which will decrease sperm PR and morphology. HPV-45, HPV-52, HPV-18, HPV-59 and HPV-16 infection seems to be major risk factors.

Male infertility microsurgical training

Microsurgical training is imperative for urologists and clinical andrologists specializing in male infertility. Success in male infertility microsurgery is heavily dependent on the surgeon＇s microsurgical skills. Laboratory-based practice to enhance microsurgical skills improves the surgeon＇s confidence, and reduces stress and operating time, benefiting both the patient and the surgeon. This review provides guidelines for setting up a microsurgical laboratory to develop and enhance microsurgical skills using synthetic and animal models. The role of emerginE techniaues, such as robotic-assisted microsureerv, is also discussed.

Chromosomal disorders and male infertility

Infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family. Despite this, the molecular and genetic factors underlying the cause of infertility remain largely undiscovered. Nevertheless, more and more genetic factors associated with infertility are being identified. This review will focus on our current understanding of the chromosomal basis of male infertility specifically： chromosomal aneuploidy, structural and numerical karyotype abnormalities and Y chromosomal microdeletions. Chromosomal aneuploidy is the leading cause of pregnancy loss and developmental disabilities in humans. Aneuploidy is predominantly maternal in origin, but concerns have been raised regarding the safety of intracytoplasmic sperm injection as infertile men have significantly higher levels of sperm aneuploidy compared to their fertile counterparts. Males with numerical or structural karyotype abnormalities are also at an increased risk of producing aneuploid sperm. Our current understanding of how sperm aneuploidy translates to embryo aneuploidy will be reviewed, as well as the application of preimplantation genetic diagnosis （PGD） in such cases. Clinical recommendations where possible will be made, as well as discussion of the use of emerging array technology in PGD and its potential applications in male infertility.

Lycopene and male infertility

Excessive amounts of reactive oxygen species （ROS） cause a state of oxidative stress, which result in sperm membrane lipid peroxidation, DNA damage and apoptosis, leading to decreased sperm viability and motility. Elevated levels of ROS are a major cause of idiopathic male factor infertility, which is an increasingly common problem today. Lycopene, the most potent singlet oxygen quencher of all carotenoids, is a possible treatment option for male infertility because of its antioxidant properties. By reacting with and neutralizing free radicals, lycopene could reduce the incidence of oxidative stress and thus, lessen the damage that would otherwise be inflicted on spermatozoa. It is postulated that lycopene may have other beneficial effects via nonoxidative mechanisms in the testis, such as gap junction communication, modulation of gene expression, regulation of the cell cycle and immunoenhancement. Various lycopene supplementation studies conducted on both humans and animals have shown promising results in alleviating male infertility--lipid peroxidation and DNA damage were decreased, while sperm count and viability, and general immunity were increased. Improvement of these parameters indicates a reduction in oxidative stress, and thus the spermatozoa is less vulnerable to oxidative damage, which increases the chances of a normal sperm fertilizing the egg. Human trials have reported improvement in sperm parameters and pregnancy rates with supplementation of 4-8 mg of lycopene daily for 3-12 months. However, further detailed and extensive research is still required to determine the dosage and the usefulness of lycopene as a treatment for male infertility.

Combined conventional/antioxidant“Astaxanthin”treatment for male infertility:a double blind,randomized trial

Aim： To evaluate the treatment of male infertility with a strong natural antioxidant, in addition to conventional treatment. Methods： Using a double blind, randomized trial design, 30 men with infertility of ≥12 months and female partners with no demonstrable cause of infertility received conventional treatment according to the guidelines of the World Health Organization （WHO）, and either a strong antioxidant Astaxanthin 16 rag/day （AstaCarox, AstaReal AB, Gustavsberg, Sweden） or placebo for 3 months. The effects of treatment on semen parameters, reactive oxygen species （ROS）, zona-free hamster oocyte test, serum hormones including testosterone, luteinizing hormone （LH）, follicle stimulating hormone （FSH） and Inhibin B, and spontaneous or intrauterine insemination （IUI）-induced pregnancies were evaluated. Results： ROS and Inhibin B decreased significantly and sperm linear velocity increased in the Astaxanthin group （n = 11）, but not in the placebo group （n = 19）. The results of the zona-free hamster oocyte test tended to improve in the Astaxanthin group in contrast with the placebo group, though not reaching statistical significance. The total and per cycle pregnancy rates among the placebo cases （10.5 % and 3.6 %） were lower compared with 54.5 % and 23. 1% respectively in the Astaxanthin group （P=0.028; P=0.036）. Conclusion： Although the present study suggests a positive effect of Astaxanthin on sperm parameters and fertility, the results need to be confirmed in a larger trial before recommending Astaxanthin for the complementary treatment of infertile men. （Asian J Androl 2005 Sep; 7： 257-262）

Prevalent false positives of azoospermia factor a （AZFa） microdeletions caused by single-nucleotide polymorphism rs72609647 in the sY84 screening of male infertility

Multiplex polymerase chain reaction （PCR） has been widely used to detect Y-chromosome micredeletions, which is one of the major causes of male infertility. Both the European Academy of Andrology （EAA） and the European Molecular Genetics Quality Network （EMQN） have recommended the use of sY84 and sY86 markers for the detection of azoospermia factor a （AZFa） microdeletion during DNA testing for male infertility. In this study, a large-scale analysis of AZF microdeletion in a total of 630 Chinese males, including healthy semen donors （n=200）, infertile males with normal sperm count （n=226） and patients with either nonobstructive azoospermia or severe oligozoospermia （n=204）, was performed. A series of nine sequence-tagged site （STS） markers from the AZF region of the Y chromosome was used to detect microdeletions. All primers were designed based on the recommendations of the National Center for Biotechnology Information. An unusually high incidence （73/630, 11.6%） of sY84-absent but sY86-present genotypes was observed in the AZFa microdeletion screening. Sequencing the sY84-flanking region revealed a total of 73 patients with sY84-absent but sY86-present genotypes have a T-to-G transversion at the fifth base from the 5＇ end of the reverse sY84 primer. These prevalent false positives, which were not only observed in infertile men, but also observed in donors, resulted from a single-nucleotide polymorphism （SNP） named rs72609647 in the targeting sequence of the reverse sY84 primer. Our study suggests that a pre-screening of existence of rs72609647 polymorphism can prevent the frequent false positive results of AZFa microdeletions detection in the infertile Chinese males. Given the SNP rs72609647 was recently found in a deep sequencing of a Chinese individual, the current EAA and EMQN standards may need to be scrutinized among different populations to avoid the potential genetic variations in the primer binding sequences.

Outcomes for offspring of men having ICSI for male factor infertility

Since the introduction of intracytoplasmic sperm injection （ICSI） using single sperm isolated from testicular tissue in men with obstructive and non-obstructive azoospermia, or using ejaculated sperm in those with poor semen quality, there have been concerns that this might have adverse effects on the offspring compared to conventional in vitrofertilisation （IVF） and natural conceptions. ICSI is done for reasons other than male factor infertility, and on the whole has not been shown to have any more negative effects than those seen with IVF. There have however, been very few studies of ICSI with a focus on, or large enough numbers to examine, the specific outcomes associated with male factor infertility. From the limited information available in relation to the source of the sperm and aetiology of infertility in the presence of ICSI, there appears to be no increased risk of congenital malformations. There is, however, a small increase in both de novoand inherited chromosome abnormalities. In terms of growth and neurodevelopment, there are very few studies, and so far, no adverse outcomes have been found in young children whose fathers have a sperm defect. The origin of the sperm used in ICSI does not have a major influence on the early life outcomes for the offspring, but transgenerational and epigenetic effects remain unknown. When the male factor infertility is known or thought to be due to a Y-chromosome deletion, this information should be given to the young male offspring at a time that will ensure his own reproductive health and plans are optimized.

Novel mutations in ubiquitin-specific protease 26 gene might cause spermatogenesis impairment and male infertility

Aim： To study the incidence of single nucleotide polymorphisms in ubiquitin-specific protease 26 （USP26） gene and its involvement in idiopathic male infertility in China. Methods： Routine semen analysis was performed. Infertility factors such as immunological, infectious and biochemical disorders were examined to select patients with idiopathic infertility. DNA was isolated from peripheral blood of the selected patients and control population, which were examined for mutations using polymerase chain reaction-single strand conformation polymorphism analysis. Furthermore, nucleotide sequences were sequenced in some patients and controls. Results： Of 41 infertile men, 9 （22.0%, P = 0.01） had changes in USP26 gene on the X chromosome. A compound mutation （364insACA; 460G→A） was detected in 8 patients （19.5%, P = 0.01） and a 1044T→A substitution was found in 1 patient （2.4%, P 〉 0.05）. All three variations led to changes in the coding amino acids. Two substitutions predict some changes： 460G→ A changes a valine into an isoleucine, and 1044T → A substitutes a leucine for a phenylalanine. Another insertion of three nucleotides ACA causes an insertion of threonine. No other changes were found in the remaining patients and fertile controls. Conclusion： The USP26 gene might be of importance in male reproduction. Mutations in this gene might be associated with male infertility, and might negatively affect testicular function. Further research on this issue is in progress.

Double versus single homologous intrauterine insemination for male factor infertility： a systematic review and meta-analysis

Male factor infertility affects 30%-50% of infertile couples worldwide, and there is an increasing interest in the optimal management of these patients. In studies comparing double and single intrauterine insemination （IUI）, a trend towards higher pregnancy rates in couples with male factor infertility was observed. Therefore, we set out to perform a meta-analysis to examine the superiority of double versus single IUI with the male partner＇s sperm in couples with male factor infertility. An odds ratio （OR） of 95% confidence intervals （CIs） was calculated for the pregnancy rate. Outcomes were analysed by using the ManteI-Haesel or DerSimonian-Laird model accordingto the heterogeneity of the results. Overall, five trials involving 1125 IUI cycles were included in the meta-analysis. There was a two-fold increase in pregnancies after a cycle with a double IUI compared with a cycle with a single IUI （OR. 2.0; 95% CI. 1.07-3.75; P〈O.03）. Nevertheless, this result was mainly attributed to the presence of a large trial that weighted as almost 50% in the overall analysis. Sensitivity analysis, excluding this large trial, revealed only a trend towards higher pregnancy rates among double IUI cycles （OR. 1.58; 95% CI. 0.59-4.21）, but without statistical significance （P=0.20）. Our systematic review highlights that the available evidence regarding the use of double IUI in couples with male factor infertility is fragmentary and weak. Although there may be a trend towards higher pregnancy rates when the number of IUIs per cycle is increased, further large and well-designed randomized trials are needed to provide solid evidence toide current clinical practice.

Proteomics of spermatogenesis： from protein lists to understanding the regulation of male fertility and infertility

Proteomic technologies have undergone significant development in recent years, which has led to extensive advances in protein research. Currently, proteomic approaches have been applied to many scientific areas, including basic research, various disease and malignant tumour diagnostics, biomarker discovery and other therapeutic applications. In addition, proteomics-driven research articles examining reproductive biology and medicine are becoming increasingly common. The key challenge for this field is to move from lists of identified proteins to obtaining biological information regarding protein function. The present article reviews the available scientific literature related to spermatogenesis. In addition, this study uses two-dimensional electrophoresis mass spectrometry （2DE-MS） and liquid chromatography （LC）-MS to construct a series of proteome profiles describing spermatogenesis. This large-scale identification of proteins provides a rich resource for elucidating the mechanisms underlying male fertility and infertility.

Male factor infertility and ART

For years, the management and treatment of male factor infertility has been ‘experience＇ and not ‘evidence＇ based. Although not evidence-based, current clinical practice involves extensive use of assisted reproductive techniques （ART）. Where specific treatments are not indicated or have failed, ART have become popular adjunctive treatments for alleviating male factor infertility. According to the limited evidence available, intrauterine insemination （IUI） may be considered as a first-line treatment in a couple in which the female partner has a normal fertility status and at least 1 × 10^6 progressively motile spermatozoa are recovered after sperm preparation. If no pregnancy is achieved after 3-6 cycles of IUI, optimized in vitro fertilization （IVF） can be proposed. When less than 0.5× 106 progressively motile spermatozoa are obtained after seminal fluid processing or sperm are recovered surgically from the testis or epididymis, intracytoplasmic sperm injection （ICSI） should be performed. Although the outcome of no other ART has ever been scrutinized as much before, no large-scale ‘macroproblems＇ have as yet been observed after ICSI. Yet, ICSI candidates should be rigorously screened before embarking on IVF or ICSI, and thoroughly informed of the limitations of our knowledge on the hereditary aspects of male infertility and the safety aspects of ART.