Teratozoospermia Research Articles

A Compound Heterozygous Pathogenic Variant in ZP2 Gene Causes Female Infertility.

The oocyte maturation defect 6 is an autosomal recessive hereditary disease caused by a homozygous variant in ZP2 gene. It is characterized by female primary infertility due to an abnormally thin zona pellucida (ZP) and defective sperm binding. Here we identified a compound heterozygous variant (c.1924C > T and c.1695-2A > G) in ZP2 gene in a Chinese Han family. Quantitative real-time PCR showed that the variant c.1924C > T significantly decreased the expression of truncated ZP2message RNA by the nonsense-mediated decay pathway. Minigene assays showed the c.1695-2A > G variant led to an extra-61-nt preservation of intron 15 at the junction between exons 15 and 16 during transcription. Both variants (c.1924C > T and c.1695-2A > G) resulted in truncated ZP2 proteins (p.R642X and p.C566Hfs*2) that lost the transmembrane domain, which prevented the secretion of the mutant ZP2 proteins and produced a structurally abnormal ZP, thus resulting in female infertility. This study further elucidated the pathogenic mechanism of these two variants and provided new support for the genetic diagnosis of female infertility.

Genetic etiological spectrum of sperm morphological abnormalities.

Male infertility manifests in the form of a reduction in sperm count, sperm motility, or the loss of fertilizing ability. While the loss of sperm production can have mixed reasons, sperm structural defects, cumulatively known as teratozoospermia, have predominantly genetic bases. The aim of the present review is to undertake a comprehensive analysis of the genetic mutations leading to sperm morphological deformities/teratozoospermia. We undertook literature review for genes involved in sperm morphological abnormalities. The genes were classified according to the type of sperm defects they cause and on the basis of the level of evidence determined by the number of human studies and the availability of a mouse knockout. Mutations in the SUN5, CEP112, BRDT, DNAH6, PMFBP1, TSGA10, and SPATA20 genes result in acephalic sperm; mutations in the DPY19L2, SPATA16, PICK1, CCNB3, CHPT1, PIWIL4, and TDRD9 genes cause globozoospermia; mutations in the AURKC gene cause macrozoospermia; mutations in the WDR12 gene cause tapered sperm head; mutations in the RNF220 and ADCY10 genes result in small sperm head; mutations in the AMZ2 gene lead to vacuolated head formation; mutations in the CC2D1B and KIAA1210 genes lead to pyriform head formation; mutations in the SEPT14, ZPBP1, FBXO43, ZCWPW1, KATNAL2, PNLDC1, and CCIN genes cause amorphous head; mutations in the SEPT12, RBMX, and ACTL7A genescause deformed acrosome formation; mutations in the DNAH1, DNAH2, DNAH6, DNAH17, FSIP2, CFAP43, AK7, CHAP251, CFAP65, ARMC2 and several other genes result in multiple morphological abnormalities of sperm flagella (MMAF). Altogether, mutations in 31 genes have been reported to cause head defects and mutations in 62 genes are known to cause sperm tail defects.

Morphological characterization of spermatozoa in Apis mellifera and the effect of processing and semen storage

The aim of this study was to establish a standardized approach for evaluating sperm morphology in the honey bee and to investigate the impact of processing techniques and semen storage on the incidence of sperm morphoanomalies. The first experiment was designed to characterize the sperm morphoanomalies in unaltered honey bee semen, examining if they are compatible with sperm motility and viability and determining their occurrence in the ejaculates of mature and healthy honey bee drones. The different forms of sperm morphoanomalies were described in detail. In the morphological analysis of fresh drone ejaculates, 7.77% of spermatozoa showed abnormal morphology on average, with 2.20%, 4.75% and 0.81% of head, tail and multiple defects, respectively. The method also allowed us to determine the status of acrosome integrity. The second experiment was designed to assess the impact of smearing and air-drying on the occurrence of sperm morphoanomalies, showing a significant increase in the incidence of both head and tail sperm defects when comparing to wet samples. In the third and fourth experiments, the effect of semen storage at room temperature and semen cryopreservation, respectively, on the occurrence of sperm morphoanomalies were investigated. The preservation of semen at 22 °C led to a significant increase in spermatozoa with coiled tails after day 1, whereas the remaining anomalies did not exhibit significant variations over time. The freezing-thawing process showed a more pronounced effect on the incidence of morphological defects, with an increase in the percentage of spermatozoa with deformed heads and coiled tails.

Study the Different Antioxidants Effects on Serum Quality in Dogs

Dogs frequently have subfertility linked to poor semen quality (high percentage of morphologically defective spermatozoa, low rate of gradual mobility and total number of sperm .To examine the anti-oxidative effect of various concentratuons of NAC on cryopreservation in dogs sperm.The animals are divided into three groups: C0, C1 and C2. C0 receives the 0mM NAC, C1 receives 0.35mM and C2 receives 0.85mM. The physical characteristics studied of the spêrm include ejaculated volume, semen color, motility of sperms, percentage of dead sperms and abnormal sperms. After physical evaluation, the samples are diluted with Tri’s diluter. The tris diluter is egg-yolk glycerol. The samples are then cryopreserved in liquid nitrogen (-196 C) from October to December. A total of 50 samples are calculated and prepared for freezing in the following way:The motility of sperm is high for 0.35mM dose of NAC, and not very different in the control group and 0.85mM NAC group. The motility is significantly different for 0.35NAC as compared to the other two groups. The p-value (< 0.05) shows the significant difference between the motility of 0.35 NAC and other groups. The sperm viability is highest in the 0.35mM NAC group (30.34). The viability of sperm is highest at 0.85mM. The membrane integrity is highest in 0.35mM NAC, while lowest in the control group( p<0.05).In conclusion, dogs sperm cells can be shielded from oxidative stress by using moderate dosages of NAC supplied in Tris extender without negatively affecting dog semen's ability to freeze.

A novel homozygous splicing mutation in AK7 causes multiple morphological abnormalities of sperm flagella in patients from consanguineous Pakistani families.

Multiple morphological abnormalities of the flagella (MMAF) represent a severe form of sperm defects leading to asthenozoospermia and male infertility. In this study, we identified a novel homozygous splicing mutation (c.871-4 ACA>A) in the adenylate kinase 7 (AK7) gene by whole-exome sequencing in infertile individuals. Spermatozoa from affected individuals exhibited typical MMAF characteristics, including coiled, bent, short, absent, and irregular flagella. Transmission electron microscopy analysis showed disorganized axonemal structure and abnormal mitochondrial sheets in sperm flagella. Immunofluorescence staining confirmed the absence of AK7 protein from the patients' spermatozoa, validating the pathogenic nature of the mutation. This study provides direct evidence linking the AK7 gene to MMAF-associated asthenozoospermia in humans, expanding the mutational spectrum of AK7 and enhancing our understanding of the genetic basis of male infertility.

Role of varicocelectomy in infertile patients with clinical varicocele and isolated sperm defects

ObjectiveThis study investigated the outcomes of microsurgical subinguinal varicocelectomy (MV) on semen and hormonal parameters in cases with isolated sperm defects (oligo-, astheno-, or terato-zoospermia). MethodsRetrospective review of charts of patients who underwent MV for clinically palpable varicocele between 2011 and 2019 at our institution was undertaken. All patients diagnosed with isolated oligo-, astheno-, or terato-zoospermia in the preoperative semen analysis were included. Men with azoospermia, history of genitourinary infection, or utilizing peri-operative fertility medications were excluded. Collected data included patient demographics, and results of routine semen analysis, DNA fragmentation, and hormone parameters (follicle stimulating hormone, luteinizing hormone, testosterone, and estradiol) before MV and up to 6 months postoperatively. ResultsA total of 331 patients with isolated sperm defects were included. Postoperatively, 83.3 % of isolated oligozoospermic patients showed a significant improvement in sperm concentration. Among isolated asthenozoospermic men, 76.7 % and 66.0 % showed postoperative significant improvement of total and progressive motility, respectively. For the teratozoospermic group, 70 % of patients showed a significant improvement in normal morphology. No changes were observed in other semen or hormone parameters that were examined. ConclusionMV is a valid and effective treatment modality for patients with isolated sperm defects that significantly corrects their respective semen abnormality and improves their chances of natural conception.

The Role of Selected Elements in Oxidative Stress Protection: Key to Healthy Fertility and Reproduction.

Oxidative stress and its relationship to fertility and reproduction is a topic of interest in medicine, especially in the context of the effects of trace elements and micronutrients. Oxidative stress occurs when there is an excess of free radicals in the body, which can lead to cell and tissue damage. Free radicals are reactive oxygen species (ROS) that can be formed as a result of normal metabolic processes, as well as under the influence of external factors such as environmental pollution, UV radiation, and diet. Oxidative stress has a significant impact on fertility. In men, it can lead to DNA damage in sperm, which can result in reduced semen quality, reduced sperm motility and increased numbers of defective sperm, and free radical damage to sperm cell membranes causing a reduction in the number of available sperm. In women, oxidative stress can affect the quality of female reproductive cells, which can lead to problems with their maturation and with embryo implantation in the uterus and can also affect ovarian function and disrupt hormonal regulation of the menstrual cycle. A proper balance of trace elements and micronutrients is key to protecting against oxidative stress and maintaining reproductive health. Supplementation with appropriate elements such as zinc, selenium, copper, manganese, chromium, and iron can help reduce oxidative stress and improve fertility. This work discusses the effects of selected elements on oxidative stress parameters specifically in terms of fertility and reproduction.

Effect of access to natural shade on scrotal thermoregulatory capacity, integrity of the testicular parenchyma and sperm morphology of Nelore (Bos indicus) and Canchim (Bos taurus x Bos indicus) bulls.

The objective of this work was to evaluate the effect of using naturally shaded pastures on scrotal thermoregulatory capacity, testicular echotexture, and sperm morphology of Nelore (Bos indicus) and Canchim (5/8 Bos taurus x 3/8 Bos indicus) bulls in a tropical climate region. Sixty-four adult Nelore and Canchim bulls were used, equally allocated in Full Sun (FS, n = 32) or Crop-Livestock-Forestry (CLF, n = 32) pasture systems. During five consecutive climate seasons, the bulls underwent monthly breeding soundness evaluations and the biometeorological variables in the systems were continuously monitored. Microclimate was significantly different between systems. CLF system had lower BGHI than FS throughout the experimental period. No triple interaction (Season x Breed x Treatment, P > 0.05) was observed for any of the variables. Animals in CLF showed lower body temperature in Summer (FS:39.41 ± 0.05 vs. CLF:39.30 ± 0.05°C; P = 0.005) and in Autumn (FS:39.54 ± 0.05 vs. CLF:39.35 ± 0.05°C; P = 0.005). Access to shading did not determine differences in the evolution of scrotal biometry, temperatures, and scrotal thermal gradients (P > 0.05). Regardless of breed, animals in CLF showed greater right testicular volume (FS:247.5 ± 5.7 vs. CLF:259.0 ± 5.7cm³; P < 0.05), more suitable parenchyma echotexture, and fewer microlithiasis spots in the Spring and Summer. Testosterone concentration was higher in FS (FS:2.6 ± 0.2 vs. CLF:2.1 ± 0.2 ng/mL; P = 0.035). Canchim bulls presented higher total sperm defects during the Autumn and Winter (P = 0.010), but the total defects levels for Canchim and Nelore bulls were in normal range for adult bulls. Thus, the natural shade in CLF system was effective in improving the microclimate of pastures and minimizing adverse environmental effects on some reproductive features of interest in beef cattle.

Relationship between season and spermatozoa traits of captive-reared agoutis from Brazilian semiarid.

For the development of efficient management and conservation strategies for wild rodent species, understanding the aspects related to their reproduction, including the interaction of this physiological function with the environment, is essential. This study aimed to evaluate the impacts of weather changes derived from a semiarid region's dry and rainy seasons on the epididymal sperm characteristics of red-rumped agouti (Dasyprocta leporina), a histricognath rodent, still little studied, which inhabits the Brazilian Caatinga. The sperm from the epididymal cauda of 14 agoutis were collected, seven individuals per season (dry and rainy). Samples were evaluated for kinetic parameters, membrane structural and functional integrity, mitochondrial activity, morphology, and morphometry. The environmental variables were measured: maximum air temperature, relative humidity, wind speed, solar radiation, and the total rainfall for dry and rainy seasons were, respectively, 36.2 and 34.1°C, 66.8 and 80.1%, 4.0 and 1.9m/s, 527.3 and 441.8 W/m2, and 0.2 and 517.7mm. There were strong correlations between some sperm parameters and environmental variables, mainly those related to the acquisition of sperm mobility. Sperm concentration and the number of sperm collected were higher in the dry (1028.7 sperm/mL × 10⁶ and 1361.2 × 106 sperm) than in the rainy season (758.9 sperm × 10⁶/mL and 714.6 sperm × 106). During the rainy season, there were fewer sperm defects, higher sperm metrics, and higher membrane structural integrity with mitochondrial activity. Regarding motility patterns, the increases during the rainy season stand out in total and progressive motility, VAP, VSL, VCL, and subpopulations of rapid sperm. In summary, our results suggest that the adverse climatic conditions of the dry season in the semiarid region, mainly high solar radiation and temperature, considerably impair the epididymal sperm quality of red-rumped agoutis. On the contrary, the largest amount of sperm was obtained during this season, probably due to compensatory and adaptive mechanisms of the species to enable its reproduction throughout the year.

AXDND1 is required to balance spermatogonial commitment and for sperm tail formation in mice and humans

Dynein complexes are large, multi-unit assemblies involved in many biological processes via their critical roles in protein transport and axoneme motility. Using next-generation sequencing of infertile men presenting with low or no sperm in their ejaculates, we identified damaging variants in the dynein-related gene AXDND1. We thus hypothesised that AXDND1 is a critical regulator of male fertility. To test this hypothesis, we produced a knockout mouse model. Axdnd1−/− males were sterile at all ages but presented with an evolving testis phenotype wherein they could undergo one round of histologically replete spermatogenesis followed by a rapid depletion of the seminiferous epithelium. Marker experiments identified a role for AXDND1 in maintaining the balance between differentiation-committed and self-renewing spermatogonial populations, resulting in disproportionate production of differentiating cells in the absence of AXDND1 and increased sperm production during initial spermatogenic waves. Moreover, long-term spermatogonial maintenance in the Axdnd1 knockout was compromised, ultimately leading to catastrophic germ cell loss, destruction of blood–testis barrier integrity and immune cell infiltration. In addition, sperm produced during the first wave of spermatogenesis were immotile due to abnormal axoneme structure, including the presence of ectopic vesicles and abnormalities in outer dense fibres and microtubule doublet structures. Sperm output was additionally compromised by a severe spermiation defect and abnormal sperm individualisation. Collectively these data identify AXDND1 as an atypical dynein complex-related protein with a role in protein/vesicle transport of relevance to spermatogonial function and sperm tail formation in mice and humans. This study underscores the importance of studying the consequences of gene loss-of-function on both the establishment and maintenance of male fertility.

P-058 The role of sperm selection in improving embryo euploidy rate: a comparison between Swim-up and Microfluidic Sperm Selection

Abstract Study question Does Microfluidic Sperm Selection (MSS) improve the blastocysts’ development rate and the euploidy rate compared to Swim-up sperm selection? Summary answer MSS doesn’t improve the rate of blastocyst development and euploidy compared to Swim-up. Furthermore, in women age ≥ 37 years D6 aneuploid blastocyst rate increases What is known already Sperm defects have been shown to have a negative impact on embryo quality and development. MSS was introduced as an alternative to traditional centrifugation-based sperm preparation techniques to efficiently isolate highly motile and healthy spermatozoa. Centrifugation has been suggested to compromise membrane integrity, motility, mitochondrial energy production, and DNA structure. Less DNA fragmentation and ROS formation was observed in spermatozoa isolated with MSS compared to standard techniques. Our study aims to analyze whether MSS also improves biological outcomes. Study design, size, duration In a prospective study of 51 ICSI/PGT-A cycles performed between September 2022 and November 2023, freshly ejaculated semen sample was divided into two aliquots and processed by Swim-up and MSS. Split sperm sample was used to inject siblings’ mature oocytes (249 vs 274 oocytes in Swim-up vs MSS groups). Inclusion criteria: retrieved MII oocytes ≥8, oligoteratozoospermic and normozoospermic semen. Results were analyzed according to women’s age &amp;lt;37 years (21 cycles) and ≥37 years (30 cycles). Participants/materials, setting, methods Spermatozoa were selected using either conventional Swim-up or a microfluidics device (ZyMōtTM). Post treatment sperm parameters (sperm count; total sperm motility; progressive motility and hyperactivated motility) were examined for both. Embryo culture was performed in Irvine Continuous Culture-NX media until day5 or day6 and biopsy was performed at the blastocyst stage by next generation sequencing. Primary endpoint was fertilization rate, blastocyst development and usable blastocysts rate. Chi-square analysis was performed and p &amp;lt; 0.05 was considered significant Main results and the role of chance There is no significant differences overall between Swim-up and MSS in fertilization rate (73% vs 75%), blastocyst development rate (47% vs 54%) and ploidy rate: aneuploid (47% vs 50%), usable blastocyst (i.e. euploid+mosaics) (53% vs 50%). When considering female age, no significant difference is observed in the primary endpoints in the &amp;lt;37 years group. However, in women aged ≥37 years, the rate of blastocyst development is similar in the two sperm preparation groups, but a significant difference is observed in the timing of blastocyst development: The percentage of blastocysts formed on day 6 in the MSS group is significantly higher than in the Swim-up group (43% vs. 19% p &amp;lt; 0.05). In addition, the aneuploidy rate of blastocysts on day 6 is also significantly higher than in the Swim-up group (79% vs. 50% respectively, p &amp;lt; 0.05). The concentration of sperm recovered post-treatment was similar in Swim-up vs MSS (23 x106 vs 19 x106); total motility and progressive motility were similar in Swim-up compared to MSS (92.7% vs. 95.3% and 85% vs. 87% respectively). Only hyperactivated motility assessed with the SCASCOPE CASA System (Microptic) was significantly higher in MSS vs Swim-up 41% vs 4% respectively (p &amp;lt; 0.0005). Limitations, reasons for caution Our study included couples with different infertility diagnosis and semen parameters. Further studies with an increased number of patients may provide more comprehensive data to better evaluate biological and clinical outcomes to eventually suggest the use of MSS in laboratory routines Wider implications of the findings Recently, some studies reported that microfluidic-sorted sperm showed significantly less ROS formation and DNA fragmentation compared to those treated with conventional Swim-up method. Nevertheless, our data does not currently show the expected increase in embryo euploidy rate to justify the routine use of these expensive devices in male infertility treatment Trial registration number non applicabile

P-001 Comparing two monomorphic teratozoospermia syndromes in terms of ICSI outcomes - Round vs. pin-head

Abstract Study question Whether ART clinical outcomes are affected at extremes of morphological presentations, in samples where typical forms are unavailable for ICSI. Summary answer The study found no correlation between the severity of sperm defect and ICSI results. What is known already One of the challenging topics in the field of Andrology is the predictive role of monomorphic teratozoospermia, specifically head defects, in assisted reproductive technology (ART) outcomes. The definitive requirement of conducting intracytoplasmic sperm injection (ICSI) is the presence of at least one motile spermatozoon. Two schools of thought provide contradicting views; some believe that sperm morphology can significantly predict fertilization, clinical pregnancy, and live birth rates in fresh ICSI cycles and others support that the degree or nature of sperm morphological dysfunction lacks a significant impact on the outcome of ICSI outcomes. Study design, size, duration This retrospective cohort study was included 7,881 couples with male factor infertility who underwent 11,536 IVF/ICSI cycles at a tertiary referral fertility center over a 13-year period. Participants/materials, setting, methods From this cohort, 10 cases were identified with &amp;gt;90% acephalic sperm syndrome and 11 patients had &amp;gt;90% globozoospermic sperm. The implantation rate, pregnancy, and live birth rates per initiated cycle (iC) and per patient were compared between the two groups. The rates were also compared between each group with the general ICSI population. Main results and the role of chance The data analysis suggests no statistically significant differences between the two patient groups. Implantation was 20% versus 15.1% (95% CI, 0.33 to 5.97; OR, 1.4) for round and pin-head groups. The pregnancy per iC and patient were 25% vs 23.1% (95% CI, 0.25 to 9.5; OR, 1.55) and 27.3% vs 30% (95% CI, 0.13 to 5.8; OR, 0.87) for round-head and pin-head groups, respectively. The live birth rates matched the pregnancy rates. For the general ICSI population the rates were as follows: implantation rate was 17.3%; pregnancy rate (per iC and per patient) was 27.2% and 44.7%; and live birth rate (per iC and per patient) was 23.2% and 38.2%. The study found no significant differences between the outcomes for the general ICSI population and the two groups. Limitations, reasons for caution It is uncertain whether this lack of association is genuine or whether it is affected by the limited number of cases with extreme monomorphic abnormalities. The absence of evidence should not be taken as evidence of absence. Wider implications of the findings Conducting such studies should be encouraged to provide insight by informing systematic reviews. A significant portion of existing literature on teratozoospermia comprises of case reports, which are rationally excluded from systematic reviews and meta-analyses. Additional research is warranted to definitively establish the investigated relationships. Trial registration number not applicable

Effects of an Anti-Fertility Product on Reproductive Structures of Common Vole Males and Residues of Compounds.

Some rodent species cause significant damage to agriculture and forestry, and some can transmit pathogens to humans and livestock. The common vole (Microtus arvalis) is widespread in Europe, and its population outbreaks have resulted in massive crop loss. Bait-based fertility control could contribute to rodent pest management. Bait containing 4-vinylcyclohexene diepoxide (VCD) and triptolide (TP), registered as ContraPest®, was delivered to male common voles for 14 or 28 consecutive days. The effects on reproductive structures and residues in the liver and testes were assessed. There was no effect on testis weight, sperm viability, sperm motility and oxidative stress in sperm cells. Results regarding the mitochondrial membrane potential of sperm, DNA fragmentation and progressively motile sperm cells were inconclusive. However, there was an increase in morphological sperm defects in voles treated for 14/28 days and fewer normal sperm cells in voles treated for 28 days. There were no TP residues in the testes, few and low TP residues and no VCD residues in liver tissues, making considerable secondary exposure to non-target species unlikely. Treatments with VCD + TP seemed to have minor effects on the reproductive organs of males. Further studies should evaluate the effect of VCD + TP on females and on the reproductive success of common voles and other pest rodent species.

Evaluation of the testicular artery Doppler velocimetry and its correlation with sperm defects in domestic cats

Several studies have demonstrated the correlation between Doppler velocimetric parameters of testicular artery and semen quality in domestic species, but in felines data are scarce. This study aimed to correlate the Doppler velocimetry of the testicular artery with sperm kinetics and sperm defects, in sedated and non-sedated cats. Forty tomcats were divided into two groups: sedated (SG; n=20) with dexmedetomidine (10 µm/kg) and ketamine (12 mg/kg), and non-sedated (NSG; n=20). The animals were subjected to ultrasound Doppler velocimetry of the distal supratesticular and marginal region of the testicular artery and subsequently orchiectomized. Epididymal tail spermatozoa were recovered and analyzed using a CASA system for motility, and morphology took place. Animals of SG presented a significantly higher velocity in the marginal region of the cat’s testicular artery [peak systolic velocity (PSV) 11.51 cm/s; end-diastolic velocity (EDV) 7.72 cm/s] compared to NSG (PSV 7.72 cm/s, P < 0.001; EDV 4.93 cm/s, P < 0.001). Sedated cats presented higher pulsatility and resistivity indexes than non-sedated cats. The supratesticular PSV of NSG was moderately correlated with major (rs = 0621; P < 0.001) and total sperm defects (rs = 0614; P < 0001). Doppler velocimetry was fairly correlated with minor, major, and total sperm defects. In conclusion, Doppler velocimetric evaluation emerges as an important possibility in the reproductive evaluation of tomcats, once the testicular artery hemodynamics were associated with sperm defects. However, it is advisable to carry out this evaluation in non-sedated animals. If sedation is necessary, peripheral vasoconstriction should be considered.

High percentage of morphological defects in sperm of the Zemplin rabbit breed: A major obstacle to fertility?

High percentage of morphological defects in sperm of the Zemplin rabbit breed: A major obstacle to fertility?

Reversible male contraception by targeted inhibition of serine/threonine kinase 33.

Men or mice with homozygous serine/threonine kinase 33 (STK33) mutations are sterile owing to defective sperm morphology and motility. To chemically evaluate STK33 for male contraception with STK33-specific inhibitors, we screened our multibillion-compound collection of DNA-encoded chemical libraries, uncovered potent STK33-specific inhibitors, determined the STK33 kinase domain structure bound with a truncated hit CDD-2211, and generated an optimized hit CDD-2807 that demonstrates nanomolar cellular potency (half-maximal inhibitory concentration = 9.2 nanomolar) and favorable metabolic stability. In mice, CDD-2807 exhibited no toxicity, efficiently crossed the blood-testis barrier, did not accumulate in brain, and induced a reversible contraceptive effect that phenocopied genetic STK33 perturbations without altering testis size. Thus, STK33 is a chemically validated, nonhormonal contraceptive target, and CDD-2807 is an effective tool compound.

Genetic Causes of Qualitative Sperm Defects: A Narrative Review of Clinical Evidence.

Several genes are implicated in spermatogenesis and fertility regulation, and these genes are presently being analysed in clinical practice due to their involvement in male factor infertility (MFI). However, there are still few genetic analyses that are currently recommended for use in clinical practice. In this manuscript, we reviewed the genetic causes of qualitative sperm defects. We distinguished between alterations causing reduced sperm motility (asthenozoospermia) and alterations causing changes in the typical morphology of sperm (teratozoospermia). In detail, the genetic causes of reduced sperm motility may be found in the alteration of genes associated with sperm mitochondrial DNA, mitochondrial proteins, ion transport and channels, and flagellar proteins. On the other hand, the genetic causes of changes in typical sperm morphology are related to conditions with a strong genetic basis, such as macrozoospermia, globozoospermia, and acephalic spermatozoa syndrome. We tried to distinguish alterations approved for routine clinical application from those still unsupported by adequate clinical studies. The most important aspect of the study was related to the correct identification of subjects to be tested and the correct application of genetic tests based on clear clinical data. The correct application of available genetic tests in a scenario where reduced sperm motility and changes in sperm morphology have been observed enables the delivery of a defined diagnosis and plays an important role in clinical decision-making. Finally, clarifying the genetic causes of MFI might, in future, contribute to reducing the proportion of so-called idiopathic MFI, which might indeed be defined as a subtype of MFI whose cause has not yet been revealed.

High percentage of midpiece defects in Brangus bull sperm with no reduction in sperm kinematics.

The study investigated midpiece defects in sperm from a 5-year-old Brangus bull with a high rate of semen batch rejection, due to morphologically abnormal sperm, with no reduction in sperm kinematics. A comprehensive evaluation was conducted over a 16-month period, involving 28 ejaculates. Notably, despite the high proportion of midpiece defects (average 37.73%, from 3% to 58%), the study revealed stable sperm production, with no discernible differences in the kinematic data before and after cryopreservation. Electron microscopy identified discontinuities in the mitochondrial sheath, characteristic of midpiece aplasia (MPA). The anomalies were attributed to be of genetic origin, as other predisposing factors were absent. Additionally, the electron microscopy unveiled plasma membrane defects, vacuoles and chromatin decondensation, consistent with previous findings linking acrosome abnormalities with midpiece defects. The findings underscored the necessity of conducting thorough laboratory evaluations before releasing cryopreserved semen for commercialization. Despite substantial morphological alterations, the initial semen evaluation data indicated acceptable levels of sperm kinematics, emphasizing the resilience of sperm production to severe morphological changes. This case report serves as a contribution to the understanding of midpiece defects in bull sperm, emphasizing the need for meticulous evaluation and quality control in semen processing and commercialization.

Identification of a novel MYO1D variant associated with laterality defects, congenital heart diseases, and sperm defects in humans.

The establishment of left-right asymmetry is a fundamental process in animal development. Interference with this process leads to a range of disorders collectively known as laterality defects, which manifest as abnormal arrangements of visceral organs. Among patients with laterality defects, congenital heart diseases (CHD) are prevalent. Through multiple model organisms, extant research has established that myosin-Id (MYO1D) deficiency causes laterality defects. This study investigated over a hundred cases and identified a novel biallelic variant of MYO1D (NM_015194: c.1531G>A; p.D511N) in a consanguineous family with complex CHD and laterality defects. Further examination of the proband revealed asthenoteratozoospermia and shortened sperm. Afterward, the effects of the D511N variant and another known MYO1D variant (NM_015194: c.2293C>T; p.P765S) were assessed. The assessment showed that both enhance the interaction with β-actin and SPAG6. Overall, this study revealed the genetic heterogeneity of this rare disease and found that MYO1D variants are correlated with laterality defects and CHD in humans. Furthermore, this research established a connection between sperm defects and MYO1D variants. It offers guidance for exploring infertility and reproductive health concerns. The findings provide a critical basis for advancing personalized medicine and genetic counseling.

Cumulus matrix selection leads to isolation of spermatozoa with better motility, morphology, and lower DNA fragmentation.

The objective of this study was to compare the motility, morphology, and levels of DNA fragmentation of spermatozoa subjected to conventional swim-up or cumulus matrix (CM) sperm selection. Semen samples were collected from 60 normozoospermic men at a private hospital between December 2021 and March 2022. After liquefaction, semen samples were separated into two portions - one part was subjected to conventional swim-up preparation and the remaining spermatozoa were subjected to CM selection. The CM was obtained by mechanical isolation from healthy donor oocytes. Semen analysis and evaluation of sperm were performed according to WHO 6th Edition Laboratory Manual and Kruger's strict criteria, respectively. Sperm DNA fragmentation (SDF, %) of the two preparations was evaluated using Halosperm G2 detection kit (Halotech, Madrid, Spain). Wilcoxon rank-sum test was used to compare the characteristics of spermatozoa obtained by the two preparations. Spermatozoa selected by CM showed significantly better rapidly progressive motility (43.5% vs. 30.6%, respectively, p<0.001), higher percentage of morphologically normal forms (14.0% vs. 9.0%, respectively, p<0.05), and lower levels of SDF (26.0% vs. 45.0%, p<0.05) in comparison to those prepared by conventional swim-up. Moreover, the incidence of multiple sperm defects was considerably lower in the samples that underwent CM selection compared to those that did not (30.0% vs. 49.0%, respectively, p<0.05).The selection by CM significantly increases sperm motility and reduces morphologically abnormal spermatozoa and DNA fragmentation rates in comparison to the conventional swim-up preparation. The application of this selection technique may increase chances of successful IVF outcomes.