Exploring the relationship between Hashimoto's thyroiditis and male fertility:A meta-analytic and meta-regression perspective on hormonal and seminal factors

Objective:To explore the relationship between Hashimoto's autoimmune hypothyroidism(HT)and male fertility,focusing on hormonal and seminal factors.Methods:A systematic literature search was conducted across databases such as PubMed,Web of Science,EMBASE,Scopus,Cochrane,and Google Scholar,covering studies published from January 2000 to March 2024.Studies investigating the impact of HT on semen quality parameters and reproductive hormones were included.Pooled effect estimates were calculated using standard mean difference(SMD)and 95%confidence intervals(CI).Results:A total of 8 studies with 8965 participants were included.HT significantly affected semen quality and reproductive hormone levels.Specifically,there was a notable decrease in progressive morphology(SMD=-0.78;95%CI:-1.40 to-0.17;P=0.01)and sperm motility(SMD=-1.151;95%CI:-1.876 to-0.425;P=0.002).In addition,there were no significant changes in reproductive hormones,although there were elevated levels of luteinizing hormone(SMD=0.437;95%CI:0.000 to 0.874;P=0.050)and follicle-stimulating hormone(SMD=0.293;95%CI:-0.171 to 0.758;P=0.216),with a slight impact on testosterone levels(SMD=-1.143;95%CI:-2.487 to 0.200;P=0.095).Conclusions:This systematic review and meta-analysis provides robust evidence of the detrimental effects of HT on semen quality and reproductive hormones,underscoring the necessity for thorough evaluation and management of thyroid function in male infertility assessments.

Pro-fertility effect of Ficus carica fruit extract in streptozotocin-induced male rats

Objective:To explore the impact of Ficus carica fruit aqueous extract on fertility parameters in streptozotocin(STZ)-induced male rats.Methods:Twenty-four male Sprague-Dawley rats were divided into four different groups.All groups except a normal control group were induced with 50 mg/kg of streptozotocin(STZ)intravenously to induce diabetes.A positive control group was treated with an antidiabetic drug,metformin(500 mg/kg)whereas a negative control group remained untreated throughout the experiment.Meanwhile,another diabetic rat group received treatment with 400 mg/kg of aqueous Ficus carica fruit extract.Rats in the treatment group were administered Ficus carica fruit aqueous extract daily through forcefeeding via oral gavage for a 21-day period.Assessments included the sperm quality(count,motility and morphology),histology of the testes,serum testosterone and fasting blood glucose(FBG)level.Results:The FBG level of the Ficus carica-treated rats exhibited a significant decrease compared to the negative control group(P<0.05).Sperm quality analysis also indicated that the aqueous Ficus carica extract had significant positive effects on sperm count and motility(P<0.05).The histology of the testes in Ficus caricatreated rats revealed an improved cell arrangement in the germinal cell layer.Furthermore,serum testosterone level showed an increment in the Ficus carica treatment group in comparison to the negative control group.Conclusions:Our findings provide compelling evidence for the profertility and anti-hyperglycemic properties of aqueous Ficus carica fruit extract in diabetic-induced male rats.

Integration of omics studies indicates that species-dependent molecular mechanisms govern male fertility

Background Comparative and comprehensive omics studies have recently been conducted to provide a comprehensive understanding of the biological mechanisms underlying infertility.However,because these huge omics datasets often contain irrelevant information,editing strategies for summarizing and filtering the data are necessary prerequisite steps for identifying biomarkers of male fertility.Here,we attempted to integrate omics data from spermatozoa with normal and below-normal fertility from boars and bulls,including transcriptomic,proteomic,and metabolomic data.Pathway enrichment analysis was conducted and visualized using g:Profiler,Cytoscape,EnrichmentMap,and AutoAnnotation to determine fertility-related biological functions according to species.Results In particular,gamete production and protein biogenesis-associated pathways were enriched in bull spermatozoa with below-normal fertility,whereas mitochondrial-associated metabolic pathways were enriched in boar spermatozoa with normal fertility.These results indicate that below-normal fertility may be determined by aberrant regulation of protein synthesis during spermatogenesis,and the modulation of reactive oxygen species generation to maintain capacitation and the acrosome reaction governs boar sperm fertility.Conclusion Overall,this approach demonstrated that distinct molecular pathways drive sperm fertility in mammals in a species-dependent manner.Moreover,we anticipate that searching for species-specific signaling pathways may aid in the discovery of fertility-related biomarkers within large omics datasets.

Distinguishing male sterile and fertile cytoplasms in indica rice(Oryza sativa L.) by OPA 12

The majority of off-type plants in in-dica hybrid rice were CMS and itsmaintainer lines.Discrimination ofmaintainer and CMS could only beconducted at heading stage.If main-tainer and CMS line could be distin-guished earlier,it would be useful toavoid yield losses caused by usingcontaminated seeds.In this study,three pairs of A and B,Minghui 63,and Fand Fplants of Zhenshan97A/Minghui 63 were used to find

Preliminary Studies on the Effect of Photoperiod and Temperature on Male Fertility of a Cytoplasmic Male Sterile Line in Wheat

[Objective] The study aimed to reveal the effect of photoperiod and temperature on male fertility of cytoplasmic male sterile line Vtai911289a in wheat and discuss the mechanism of male fertility alteration. [ Method ] The sowing-date tests and designed conditions were conducted during 2003 -2005. [ Result] Fertility of Vtai911289a, could alter under specific photoperiod and temperature conditions. Temperature is one of the main factors influencing male fertility of the male sterile lines. Vtai911289a, showed stable sterility under the condition of the mean of daily temperature at fertility sensitive stage lower than 19℃ and presented partial fertility when the mean of daily temperature at fertility sensitive stage lower than 20 - 22℃. Photoperiod to some extent affects the male fertility of Vtai911289a, long-day condition is helpful for the male fertility of the sterile line. [ Conclusion] The application of photoperiod temperature-sensitive cytoplasmic male sterile line in production has a higher safety than that of temperature sensitive sterile line.

Resolution of sperm quality impairment following SARS-CoV-2 infection:A prospective study

Objective:To investigate the length of time required to resolve COVID-19 effects on semen quality and DNA integrity.Methods:A prospective cohort study was conducted among 42 men who tested positive for SARS-CoV-2 and underwent semen analysis at baseline and four months’post-recovery.Semen samples were collected and evaluated for macroscopic and microscopic parameters,sperm chromatin maturation,and DNA fragmentation.Results:The mean age of participants was 37(±7)years,and 14%had normozoospermia at baseline.After a four-month recovery from COVID-19,48%of patients had normozoospermia.Sperm count,motility,and morphology increased significantly,while sperm DNA fragmentation and sperm chromatin maturation decreased significantly post-recovery from COVID-19.Conclusions:Sperm parameters improve after a four-month recovery from COVID-19.The findings indicate significant improvements in sperm count,motility,morphology,DNA fragmentation,and chromatin maturation after a four-month recovery period.

Normal sperm head morphometric reference values in fertile Asian males

Sperm head morphology is crucial for male factor infertility diagnosis and assessment of male reproductive potential.Severalcriteria are available to analyze sperm head morphology,but they are limited by poor methodology comparability and populationapplicability.This study aimed to explore comprehensive and new normal morphometric reference values for spermatozoa heads infertile Asian males.An automated sperm morphology analysis system captured 23152 stained spermatozoa from confirmed fertilemales.Of these samples,1856 sperm head images were annotated by three experienced laboratory technicians as“normal”.Weemployed 14 novel morphometric features to describe sperm head size(head length,head width,length/width ratio,and girth),shape(ellipse intersection over union,girth intersection over union,short-axis symmetry,and long-axis symmetry),area(head,acrosome,postacrosomal areas,and acrosome area ratio),and degrees of acrosome and nuclear uniformity.This straight-forwardmethod for the morphometric analysis of sperm by accurate visual measurements is clinically applicable.The measured parameterspresent valuable information to establish morphometric reference intervals for normal sperm heads in fertile Asian males.Thepresented detailed measurement data will be valuable for interlaboratory comparisons and technician training.In vitro fertilizationand andrology laboratory technicians can use these parameters to perform objective morphology evaluation when assessing malefertilization potential.

Determination of sperm acrosin activity for evaluation of male fertility

Aim: To investigate a simple method for assaying acrosin activity for the evaluation of male fertility. Methods:The acrosin activity of 7.5 × 10~6 sperm without seminal plasma and acrosin activity inhibitors was assayed using N-α-benzoyl-DL-arginine-p-nitroanilide (BAPNA) and detergent (Triton X-100) as substrate. Results: The acrosin ac-tivity of 60 normal fertile men (35 ± 10 μIU/10~6 sperm ) was higher than that of 168 infertile men ( 16 ± 8 μIU/10~6sperm) (P <0.01). It was indicated that there was a significant positive correlation between the acrosin activity andthe sperm motility ( r ≥ 0.6534, P < 0.01) and a significant negative correlation between the sperm malformed rateand the WBC number ( r ≤ -0.5426, P < 0.01). The temperature and time of incubation and the sperm concentrationcould influence the assay results. Conclusion: Acrosin activity is an important index for the evaluation of male fer-tility. The approach developed by the authors is a simple method for the determination of acrosin activity.

Function of seminal vesicles and their role on male fertility

The present review has been designed to update the recent developments on the function of seminal vesicles andtheir role on male fertility. It is indicated that the true corrected fructose level is a simple method for the assessment ofthe seminal vesicular function. Measurement of seminal fructose used universally as a marker of the seminal vesiclefunction is not an appropriate approach due to its inverse relationship with the sperm count. The true corrected fructosedefined as [log. motile sperm concentration] multiplied by [seminal fructose concentration] has been shown to be abetter marker of the seminal vesicle function. Seminal vesicular secretion is important for semen coagulation, sperm motility, and stability of sperm chromatinand suppression of the immune activity in the female reproductive tract. In conclusion, the function of seminal vesicle is important for fertility. Parameters as sperm motility, sperm chro-matin stability, and immuno-protection may be changed in case of its hypofunction. (Asian J Androl 2001 Dec; 3:251 -258)

Evidence that chronic hypoxia causes reversible impairment on male fertility

Aim： To evaluate the effect of chronic hypoxia on human spermatogenic parameters and their recovery time. Methods： Seminological parameters of six male healthy mountain trekkers were evaluated in normoxia at sea level. After 26 days exposure to altitude （ranging from 2 000 m to 5 600 m, Karakorum Expedition） the same parameters were again evaluated after returning to sea level. These parameters were once again evaluated after 1 month and then again after 6 months. Results： Sperm count was found to be lower immediately after returning to sea level （P = 0.0004） and again after a month （P = 0.0008）. Normal levels were reached after 6 months. Spermatic motility （%） shows no reduction immediately after returning to sea level （P = 0.0583）, whereas after 1 month this reduction was significant （P = 0.0066）. After 6 months there was a recovery to pre-hypoxic exposure values. Abnormal or immature spermatozoa （%） increased immediately after returning to sea level （P = 0.0067） and then again after 1 month （P = 0.0004）. After 6 months there was a complete recovery to initial values. The total number of motile sperm in the ejaculate was found to be lower immediately after returning to sea level （P = 0.0024） and then again after 1 month （P = 0.0021）. After 6 months there was a recovery to pre-hypoxic exposure values. Conclusion： Chronic hypoxia induces a state of oligospermia and the normalization of such seminological parameters at the restoration of previous normoxic conditions after 6 months indicate the influence of oxygen supply in physiological mechanisms of spermatogenesis and male fertility.

Pro-oxidative and anti-oxidative imbalance in human semen and its relation with male fertility

Oxidative stress is a common condition suffered by biological systems in aerobic conditions. Human semen also has its own molecular guard against the free radicals created by normal respiratory process or from immune reactions. The equilibrium of the creation and scavenging of free radicals is mandatory in the spermatozoa to fertilize and initiate a full-term pregnancy. The paper is a systematic review of publications that evaluate oxidative stress in semen. The Cochrane Library, Medline (1966-2003), Embase (1988-2003), SciSearch (1981-2003) and the conference papers were searched. When sperm samples from fertile and infertile males were analyzed, some of the mechanisms that determine the oxidative stress level were found to be impaired while others were unaltered. In conclusion, the literature as a whole provides contradictory findings and it is necessary to carry out more work to identify all the enzymatic and non-enzymatic systems involved in oxidative stress in the ejaculate, in order to develop new diagnostic systems and therapeutic strategies for combating detrimental free radical imbalance in the semen.

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.

Mouse models in male fertility research

Limited knowledge of the genetic causes of male infertility has resulted in few treatment and targeted therapeutic options. Although the ideal approach to identify infertility causing mutations is to conduct studies in the human population, this approach has progressed slowly due to the limitations described herein. Given the complexity of male fertility, the entire process cannot be modeled in vitro. As such, animal models, in particular mouse models, provide a valuable alternative for gene identification and experimentation. Since the introduction of molecular biology and recent advances in animal model production, there has been a substantial acceleration in the identification and characterization of genes associated with many diseases, including infertility. Three major types of mouse models are commonly used in biomedical research, including knockoutJknockin/gene-trapped, transgenic and chemical-induced point mutant mice. Using these mouse models, over 400 genes essential for male fertility have been revealed. It has, however, been estimated that thousands of genes are involved in the regulation of the complex process of male fertility, as many such genes remain to be characterized. The current review is by no means a comprehensive list of these mouse models, rather it contains examples of how mouse models have advanced our knowledge of post-natal germ cell development and male fertility regulation.

Diagnostic tools in male infertility--the question of sperm dysfunction

Sperm dysfunction is the single most common cause of infertility, yet what is remarkable is that, there is no drug a man can take or add to his spermatozoa in vitroto improve fertility. One reason for the lack of progress in this area is that our understanding of the cellular and molecular workings of the mature spermatazoon is limited. However, over the last few years there has been considerable progress in our knowledge base and in addressing new methods to diagnose sperm dysfunction. We review the current state of the field and provide insights for further development. We conclude that： （i） there is little to be gained from more studies identifying/categorizing various populations of men using a basic semen assessment, where an effort is required in making sure the analysis is performed in an appropriate high quality way; （ii） technological development is likely to bring the reality of sperm function testing closer to implementation into the clinical pathways. In doing this, these assays must be robust, cheap （or more appropriately termed cost effective）, easy to use and clinically useful; and （iii） clinical necessity, e.g., the need to identify the highest quality spermatozoon for injection is driving basic research forward. This is an exciting time to be an andrologist and, likely, a fruitful one.

Drug treatment of male fertility disorders

Drug treatment remains an active domain in the therapy of male fertility disorders. Although there are only a fewconditions that allow causal treatment, rational approaches are possible in many cases. Best results are obtained in casesrequiring an anti-inflammatory treatment and in patients with an impaired sperm transport. High-dosage administrationof FSH is a promising new development, aimed particularly at improving the disturbed sperm structures. A careful di-agnostic work-up with elucidation of the underlying disease is essential to achieve a successful therapy.

Genome-wide analyses on transcription factors and their potential microRNA regulators involved in maize male fertility

Anther development is a programmed biological process crucial to plant male reproduction. Genomewide analyses on the functions of transcriptional factor(TF) genes and their microRNA(miRNA) regulators contributing to anther development have not been comprehensively performed in maize. Here, using published RNA-Seq and small RNA-Seq(sRNA-Seq) data from maize anthers at ten developmental stages in three genic male-sterility(GMS) mutants(ocl4, mac1, and ms23) and wild type W23, as well as newly sequenced maize anther transcriptomes of ms7-6007 and lob30 GMS mutants and their WT lines, we analyzed and found 1079 stage-differentially expressed(stage-DE) TF genes that can be grouped into six(premeiotic, meiotic, postmeiotic, premeiotic-meiotic, premeiotic-postmeiotic, and meiotic-postmeiotic clusters) expression clusters. Functional enrichment combined with cytological and physiological analyses revealed specific functions of genes in each expression cluster. In addition, 118 stage-DE miRNAs and99 miRNA-TF gene pairs were identified in maize anthers. Further analyses revealed the regulatory roles of zma-miR319 and zma-miR159 as well as ZmMs7 and ZmLOB30 on ZmGAMYB expression. Moreover,ZmGAMYB and its paralog ZmGAMYB-2 were demonstrated as novel maize GMS genes by CRISPR/Cas9 knockout analysis. These results extend our understanding on the functions of miRNA-TF gene regulatory pairs and GMS TF genes contributing to male fertility in plants.

Medical treatment of idiopathic oligozoospermia and male factor subfertility

Pharmaceutical treatment for the so-called idiopathic oligozoospermia (I. O.) is possible and effective in a fairproportion of patients with the syndrome provided that appropriate investigative procedures may identify the major disor-der or its level of disruption, this abnormality is reversible and appropriate prognostic indices for the treatment's successare devised and validated. According to the evidence available, minimal evaluation and prognostic indices for treatmenteligibility in normogonadotropic men with I.O. include a routine work-up but, mainly, microscopical assessment ofspermatogenesis and appraisal of Sertoli cell's functional capacity. Published data indicate that men with hypospermato-genesis without maturational arrest, respond favorably to agents stimulating Sertoli cells and germinal epithelium withincreased sperm production. Furthermore, Sertoli cell activity as judged by cell-specific indices such as inhibin B secre-tion, may provide additional discriminating power to the microscopical picture of the testis. In this context, precise i-dentification of the causative factor(s), together with the establishment of prognostic indices are the most important cri-teria on which the decision, for or against medical treatment in I. O., should be based. Obviously, further basic re-search and clinical trials are urgently needed in this particular field, and this should be a major task for clinical androlo-gists. (Asian J Androl 2000; 2: 25 - 32)

Treatment of hypogonadotropic male hypogonadism: Case-based scenarios

The aim of this study is to review four case-based scenarios regarding the treatment of symptomatic hypogonadism in men. The article is designed as a review of published literature. We conducted a PubMed literature search for the time period of 1989-2014, concentrating on 26 studies investigating the effcacy of various therapeutic options on semen analysis, pregnancy outcomes, time to recovery of spermatogenesis, as well as serum and intratesticular testosterone levels. Our results demonstrated thatexogenous testosterone suppresses intratesticular testosterone production, which is an absolute prerequisite for normal spermatogenesis. Cessation of exogenous testosterone should be recommended for men desiring to maintain their fertility. Therapies that protect the testis involve human chorionic gonadotropin （hCG） therapy or selective estrogen receptor modulators （SERMs）, but may also include low dose hCG with exogenous testosterone. Off-label use of SERMs, such as clomiphene citrate, are effective for maintaining testosterone production long-term and offer the convenience of representing a safe, oral therapy. At present, routine use of aromatase inhibitors is not recommended based on a lack of long-term data. We concluded that exogenous testosterone supplementation decreases sperm production. It was determined that clomiphene citrate is a safe and effective therapy for men who desire to maintain fertility. Although less frequently used in the general population, hCG therapy with or without testosterone supplementation represents an alternative treatment.

Cytological study on haploid male fertility in maize

Doubled haploid(DH)breeding technology,which relies on haploid genome doubling,is widely used in commercial maize breeding.Spontaneous haploid genome doubling(SHGD),a more simplified and straightforward method,is gaining popularity among maize breeders.However,the cytological mechanism of SHGD remains unclear.This study crossed inbred lines RL36 and RL7,which have differing SHGD abilities,with inducer line YHI-1 to obtain haploid kernels.The meiotic processes of pollen mother cells(PMCs)in the haploid plants were compared with diploid controls.The results suggested that three main pathways,the early doubling of haploid PMCs,the first meiotic metaphase chromosomal segregation distortion,and anomaly of the second meiosis,are responsible for SHGD.Furthermore,flow cytometry analysis of ploidy levels in leaves and PMCs from haploids and diploid controls revealed that somatic cell chromosome doubling and germ cell chromosome doubling are independent processes.These findings provide a foundation for further studies on the underlying mechanism of SHGD,aiding the application of DH technology in maize breeding practices.

FSHR Gene Polymorphisms Causes Male Infertility

Prior studies suggested sperm with damaged DNA permits fertilization but may lead to failure of embryo implantation following blastocyst formation. Quantitative correlations between DNA damage and risk of implantation failure have, however, so far not been performed. The aim of this study was to investigate two FSHR gene polymorphisms G919A (Ala307Thr) and A2039G (Asn680Ser) in Eastern Ukrainian Caucasian men with abnormally low fertility. The molecular genetic analysis was performed by real-time PCR, with the level of DNA fragmentation measured by the sperm chromatin dispersion (SCD) method. The relationship between DNA fragmentation in sperm and these genetic polymorphisms was estimated. Compared to homozygotes, the risk of high-level DNA fragmentation (>20%) increased in men up to age 35 years 16-fold for heterozygotes GA of polymorphic variant G919A, 28-fold for homozygotes AA of polymorphic variant G919A;and 16-fold for heterozygotes GG of polymorphic variant A2039G. A statistically significant positive correlation between number of alternative alleles of the FSHR gene in genotype and degree of DNA fragmentation is proved (rs = 0.70, P < 0.01).