Idiopathic oligoasthenoteratozoospermia （iOAT） affects approximately 30% of all infertile men. This mini-review discussed recent data in this field. Age, non-inflammatory functional alterations in post-testicular or...Idiopathic oligoasthenoteratozoospermia （iOAT） affects approximately 30% of all infertile men. This mini-review discussed recent data in this field. Age, non-inflammatory functional alterations in post-testicular organs, infective agents （Chlamydia trachomatis, herpes virus and adeno-associated viruses）, alterations in gamete genome, mitochondrial alterations, environmental pollutants and ＂subde＂ hormonal alterations are all considered possible causes of iOAT. Increase of reactive oxygen species in tubules and in seminal plasma and of apoptosis are reputed to affect sperm concentration, motility and morphology, iOAT is commonly diagnosed by exclusion, nevertheless spectral traces of the main testicular artery may be used as a diagnostic tool for iOAT. The following can be considered therapies for iOAT： 1） tamoxifen citrate （20 mg/d） ＋ testosterone undecanoate （120 mg/d） （pregnancy rate per couple/month [prcm]： 3.8%）; 2） folic acid （66 mg/d） ＋ zinc sulfate （5 mg/d）; 3） L-carnitine （2 g/d） alone or in combination with acetyl-L- canitine （1 g/d） （prcm： 2.3%）; and 4） both camitines ＋ one 30 mg cinnoxicam suppository every 4 days （prcm： 8.5%）. Alpha-blocking drugs improved sperm concentration but not morphology, motility or pregnancy rate. Tranilast （300 mg/d） increased sperm parameters and pregnancy rates in an initial uncontrolled study. Its efficacy on sperm concentration （but not on sperm motility, morphology or prcm） was confirmed in subsequent published reports. The efficacy of tamoxifen ＋ testosterone undecanoate, tamoxifen alone, and recombinant follicle-stimulating hormone is still a matter for discussion. （Asian J Andro12006 Mar; 8： 143-157）展开更多
To evaluate the level of antisperm antibody （ASA） in infertile men with oligoasthenoteratozoospermia （OAT）. Methods Forty-six infertile men with OAT were enrolled into this study. Sperm samples were screened by th...To evaluate the level of antisperm antibody （ASA） in infertile men with oligoasthenoteratozoospermia （OAT）. Methods Forty-six infertile men with OAT were enrolled into this study. Sperm samples were screened by the direct immunobead test for ASA type IgG and lgA according to the WHO laboratory manual. Results Of the 46 patients with OAT assessed for ASA-IgG, 2 had immunobead binding which were 22% and 27%, respectively, and the sub-positive rate was 4.3%. No case had the clinical positive level according to the WHO criteria （ ≥ 50% of the motile sperm with immunobead binding）. ASA-IgA was not detected in all cases. Conclusion A significant incidence or high level of ASA could not be found in infertile men with OAT, which suggests that ASA is not associated with the pathogenesis of infertile men with OAT.展开更多
Male infertility is a worldwide health issue,affecting 8%–12%of the global population.Oligoasthenoteratozoospermia(OAT)represents a severe type of male infertility,characterized by reduced sperm count and motility an...Male infertility is a worldwide health issue,affecting 8%–12%of the global population.Oligoasthenoteratozoospermia(OAT)represents a severe type of male infertility,characterized by reduced sperm count and motility and an increased frequency of sperm with aberrant morphology.Using whole-exome sequencing,this study identified a novel missense mutation(c.848C>A,p.A283E)in the coiled-coil domain-containing 34 gene(CCDC34)in a consanguineous Pakistani family.This rare mutation was predicted to be deleterious and to affect the protein stability.Hematoxylin and eosin staining of spermatozoa from the patient with OAT revealed multiple morphological abnormalities of the flagella and transmission electron microscopy indicated axonemal ultrastructural defects with a lack of outer dynein arms.These findings indicated that CCDC34 plays a role in maintaining the axonemal ultrastructure and the assembly or stability of the outer dynein arms,thus expanding the phenotypic spectrum of CCDC34 missense mutations.展开更多
Oxidative stress is one of the main mechanisms responsible for male infertility.Various conditions such as varicocele,obesity,advanced age,and lifestyle can lead to an increase in reactive oxygen species,causing an ox...Oxidative stress is one of the main mechanisms responsible for male infertility.Various conditions such as varicocele,obesity,advanced age,and lifestyle can lead to an increase in reactive oxygen species,causing an oxidative imbalance in the reproductiveenvironment.Spermatozoa are sensitive to reactive oxygen species and require energy to carry out their main function of fertilizingthe egg.Excessive reactive oxygen species can affect sperm metabolism,leading to immobility,impaired acrosome reaction,and celldeath,thereby impairing reproductive success.This double-blind randomized study evaluated the effect of supplementation withL-carnitine,acetyl-L-carnitine,vitamins,and other nutrients on semen quality in 104 infertile patients with or without varicocele,while also investigating the impact of factors such as obesity and advanced age on treatment.Sperm concentration significantlyincreased in the supplemented group compared to the placebo group(P=0.0186).Total sperm count also significantly increasedin the supplemented group(P=0.0117),as did sperm motility(P=0.0120).The treatment had a positive effect on patients upto 35 years of age in terms of sperm concentration(P=0.0352),while a body mass index(BMI)above 25 kg m^(−2) had a negativeeffect on sperm concentration(P=0.0110).Results were not showing a net benefit in stratifying patients in accordance withtheir BMI since sperm quality increase was not affected by this parameter.In conclusion,antioxidant supplementation may bebeneficial for infertile patients and has a more positive effect on younger patients with a normal weight.展开更多
Glutathione peroxidase (GPx) is an antioxidant that plays an important role in the maintenance of male fertility. The aim of this study was to compare the profile of enzymatic activity of glutathione peroxidase in the...Glutathione peroxidase (GPx) is an antioxidant that plays an important role in the maintenance of male fertility. The aim of this study was to compare the profile of enzymatic activity of glutathione peroxidase in the seminal plasma of normozoosperm and those of pathological sperm. Thus, the activity of glutathione peroxidase was determined in the seminal plasma of 20 normozoosperms, 9 azoosperms and 31 oligoasthenoteratozoosperms. It was 37.58 ± 3.14 U/L in normozoosperms, 39.39 ± 2.27 U/L in oligoasthenoteratozoosperms, and 29.77 ± 2.62 U/L in azoosperms. The mean GPx enzyme activity of normozoosperms did not differ significantly from that of oligoasthenoteratozoosperms and azoosperms. In contrast, comparison of enzyme activity between abnormal sperms gave a significant difference. This study showed that glutathione peroxidase enzymatic activity is not related to sperm quality.展开更多
Aims: To determine the impact of varicocele on the result of the spermogram in a group of hypo-fertile or infertile men. Patients and Method: This was a cross-sectional, descriptive study concerning 264 men collected ...Aims: To determine the impact of varicocele on the result of the spermogram in a group of hypo-fertile or infertile men. Patients and Method: This was a cross-sectional, descriptive study concerning 264 men collected between February 2020 and March 2022 at the Fertilia medical clinic in Bamako. The study population consisted of consenting male subjects presenting for infertility. All of our patients had already done a spermogram, they then benefited from a scrotal Doppler ultrasound. The scrotal echo-doppler was completed by an abdominal and pelvic echography in search of a possible etiology, in particular a renal cancer, a thrombosis of the renal or spermatic vein, a retroperitoneal mass or a nutcraker syndrome. Testicular volume was measured on ultrasound according to Lambert’s formula (length × width × height × 0.71). A volume = 16 ml was considered normal. Results: 264 patients were recruited in ours. The average age was 33 years with extremes ranging from 25 to 65 years. 149 patients or 56.44% were between 30 and 45 years old. 213 patients or 80.68% had primary infertility. All the patients, i.e. 100%, had a sperm anomaly and dilation of the pampiniform plexus veins. The most common sperm abnormalities were oligoasthenoteratozoospermia, which concerned 214 patients, or 81%, followed by azoospermia (40 patients, or 15%) and oligospermia (10 patients, or 4%). 213 patients or 80.68% had a Hirshen grade II varicocele, 45 patients or 17% had grade I and 06 patients or 2.27% had grade III. Among the 6 patients, 04 had left testicular atrophy and 2 bilateral atrophy. The venous reflux was more accentuated on the left than on the right. Conclusion: Varicocele is significantly found in men with infertility. Sperm alterations concern both the concentration of spermatozoa, their mobility and their vitality. Even if the mechanism of alteration of the sperm parameters is not well elucidated, our study made it possible to make the link between the dilation of the veins of the pampiniform plexus and the sperm abnormal展开更多
Infertility represents a significant health concern,with sperm quantity and quality being crucial determinants of male fertility.Oligoasthenoteratozoospermia(OAT)is characterized by reduced sperm motility,lower sperm ...Infertility represents a significant health concern,with sperm quantity and quality being crucial determinants of male fertility.Oligoasthenoteratozoospermia(OAT)is characterized by reduced sperm motility,lower sperm concentration,and morphological abnormalities in sperm heads and flagella.Although variants in several genes have been implicated in OAT,its genetic etiologies and pathogenetic mechanisms remain inadequately understood.In this study,we identified a homozygous nonsense mutation(c.916C>T,p.Arg306*)in the coiled-coil domain containing 146(CCDC146)gene in an infertile male patient with OAT.This mutation resulted in the production of a truncated CCDC146 protein(amino acids 1-305),retaining only two out of five coiled-coil domains.To validate the pathogenicity of the CCDC146 mutation,we generated a mouse model(Ccdc146^(mut/mut))with a similar mutation to that of the patient.Consistently,the Ccdc146mut/mut mice exhibited infertility,characterized by significantly reduced sperm counts,diminished motility,and multiple defects in sperm heads and flagella.Furthermore,the levels of axonemal proteins,including DNAH17,DNAH1,and SPAG6,were significantly reduced in the sperm of Ccdc146^(mut/mut) mice.Additionally,both human and mouse CCDC146 interacted with intraflagellar transport protein 20(IFT20),but this interaction was lost in the mutated versions,leading to the degradation of IFT20.This study identified a novel deleterious homozygous nonsense mutation in CCDC146 that causes male infertility,potentially by disrupting axonemal protein transportation.These findings offer valuable insights for genetic counseling and understanding the mechanisms underlying CCDC146 mutant-associated infertility in human males.展开更多
Oligoasthenoteratozoospermia is an important factor affecting male fertility and has been found to be associated with genetic factors.However,there are stll a proportion of oligoasthenoteratozoospermia cases that cann...Oligoasthenoteratozoospermia is an important factor affecting male fertility and has been found to be associated with genetic factors.However,there are stll a proportion of oligoasthenoteratozoospermia cases that cannot be explained by known pathogenic genetic variants.Here,we perform genetic analyses and identify bi-allelic loss-of-function variants of MFSD6L from an oligoasthenoteratozoospermia-affected family.Mfsd6l knock-out male mice also present male subfertility with reduced sperm concentration,motility,and deformed acrosomes.Further mechanistic analyses reveal that MFsD6L,as an acrosome membrane protein,plays an important role in the formation of acrosome by interacting with the inner acrosomal membrane protein SPACA1.Moreover,poor embryonic development is consistently observed after intracytoplasmic sperm injection treatment using spermatozoa from the MFSD6L-deficient man and male mice.Collectively,our findings reveal that MFSD6L is required for the anchoring of sperm acrosome and head shaping.The deficiency of MFsD6L affects male fertility and causes oligoasthenoter-atozoospermia in humans and mice.展开更多
Intracytoplasmic sperm injection(ICSI)efficiently addresses male factor infertility.However,the occurrence of abnormal fertilization,mainly characterized by abnormal pronuclei(PN)patterns,merits investigation.To inves...Intracytoplasmic sperm injection(ICSI)efficiently addresses male factor infertility.However,the occurrence of abnormal fertilization,mainly characterized by abnormal pronuclei(PN)patterns,merits investigation.To investigate abnormal fertilization patterns following ICSI and identify their respective associations with abnormal parameters in semen analysis(SA),a retrospective observational study including 1855 cycles was performed.Male infertility diagnosis relied on the 2010 WHO criteria.The population was divided into groups based on their SA results.The presence of 2PNs and extrusion of the second polar body(PB)indicated normal fertilization.A Kruskal–Wallis test along with a Wilcoxon post hoc evaluation and Bonferroni correction was employed for comparison among the groups.For the pregnancy rate,logistic regression was employed.No correlation was established between the SA abnormalities and the 1PN or 3PN formation rates.The highest and lowest 0PN rates were reported for the oligoasthenoteratozoospermic and normal groups,respectively.The lowest cleavage formation rates were identified in the oligoasthenozoospermic and oligoasthenoteratozoospermic groups.The aforementioned groups along with the oligoteratozoospermic group similarly presented the lowest blastocyst formation rates.For the clinical pregnancy rate,no statistically significant difference was observed.In conclusion,the incidence of two or more abnormal SA parameters–with the common denominator being oligozoospermia–may jeopardize normal fertilization,cleavage,and blastocyst rates.Once the developmental milestone of achieving blastocyst stage status was achieved,only oligoasthenozoospermia and oligoasthenoteratozoospermia were associated with lower rates.Interestingly,following adjustment for the number of blastocysts,no statistically significant differences were observed.展开更多
Oligoasthenoteratozoospermia(OAT)refers to the combination of various sperm abnormalities,including a decreased sperm count,reduced motility,and abnormal sperm morphology.Only a few genetic causes have been shown to b...Oligoasthenoteratozoospermia(OAT)refers to the combination of various sperm abnormalities,including a decreased sperm count,reduced motility,and abnormal sperm morphology.Only a few genetic causes have been shown to be associated with OAT.Herein,we identified a novel homozygous frameshift mutation in meiosis-specific nuclear structural 1(MNS1;NM_018365:c.603_604insG:p.Lys202Glufs*6)by whole-exome sequencing in an OAT proband from a consanguineous Chinese family.Subsequent variant screening identified four additional heterozygous MNS1 variants in 6/219 infertile individuals with oligoasthenospermia,but no MNS1 variants were observed among 223 fertile controls.Immunostaining analysis showed MNS1 to be normally located in the whole-sperm flagella,but was absent in the proband's sperm.Expression analysis by Western blot also confirmed that MNS1 was absent in the proband's sperm.Abnormal flagellum morphology and ultrastructural disturbances in outer doublet microtubules were observed in the proband's sperm.A total of three intracytoplasmic sperm injection cycles were carried out for the proband's wife,but they all failed to lead to a successful pregnancy.Overall,this is the first study to report a loss-of-function mutation in MNS1 causing OAT in a Han Chinese patient.展开更多
文摘Idiopathic oligoasthenoteratozoospermia （iOAT） affects approximately 30% of all infertile men. This mini-review discussed recent data in this field. Age, non-inflammatory functional alterations in post-testicular organs, infective agents （Chlamydia trachomatis, herpes virus and adeno-associated viruses）, alterations in gamete genome, mitochondrial alterations, environmental pollutants and ＂subde＂ hormonal alterations are all considered possible causes of iOAT. Increase of reactive oxygen species in tubules and in seminal plasma and of apoptosis are reputed to affect sperm concentration, motility and morphology, iOAT is commonly diagnosed by exclusion, nevertheless spectral traces of the main testicular artery may be used as a diagnostic tool for iOAT. The following can be considered therapies for iOAT： 1） tamoxifen citrate （20 mg/d） ＋ testosterone undecanoate （120 mg/d） （pregnancy rate per couple/month [prcm]： 3.8%）; 2） folic acid （66 mg/d） ＋ zinc sulfate （5 mg/d）; 3） L-carnitine （2 g/d） alone or in combination with acetyl-L- canitine （1 g/d） （prcm： 2.3%）; and 4） both camitines ＋ one 30 mg cinnoxicam suppository every 4 days （prcm： 8.5%）. Alpha-blocking drugs improved sperm concentration but not morphology, motility or pregnancy rate. Tranilast （300 mg/d） increased sperm parameters and pregnancy rates in an initial uncontrolled study. Its efficacy on sperm concentration （but not on sperm motility, morphology or prcm） was confirmed in subsequent published reports. The efficacy of tamoxifen ＋ testosterone undecanoate, tamoxifen alone, and recombinant follicle-stimulating hormone is still a matter for discussion. （Asian J Andro12006 Mar; 8： 143-157）
文摘To evaluate the level of antisperm antibody （ASA） in infertile men with oligoasthenoteratozoospermia （OAT）. Methods Forty-six infertile men with OAT were enrolled into this study. Sperm samples were screened by the direct immunobead test for ASA type IgG and lgA according to the WHO laboratory manual. Results Of the 46 patients with OAT assessed for ASA-IgG, 2 had immunobead binding which were 22% and 27%, respectively, and the sub-positive rate was 4.3%. No case had the clinical positive level according to the WHO criteria （ ≥ 50% of the motile sperm with immunobead binding）. ASA-IgA was not detected in all cases. Conclusion A significant incidence or high level of ASA could not be found in infertile men with OAT, which suggests that ASA is not associated with the pathogenesis of infertile men with OAT.
基金supported by the National Natural Science Foundation of China(No.82071709,No.32070850,and No.82171601)the National Key Research and Developmental Program of China(2022YFC2702601 and 2022YFA0806303)the Joint Fund for New Medicine of USTC(YD9100002034).
文摘Male infertility is a worldwide health issue,affecting 8%–12%of the global population.Oligoasthenoteratozoospermia(OAT)represents a severe type of male infertility,characterized by reduced sperm count and motility and an increased frequency of sperm with aberrant morphology.Using whole-exome sequencing,this study identified a novel missense mutation(c.848C>A,p.A283E)in the coiled-coil domain-containing 34 gene(CCDC34)in a consanguineous Pakistani family.This rare mutation was predicted to be deleterious and to affect the protein stability.Hematoxylin and eosin staining of spermatozoa from the patient with OAT revealed multiple morphological abnormalities of the flagella and transmission electron microscopy indicated axonemal ultrastructural defects with a lack of outer dynein arms.These findings indicated that CCDC34 plays a role in maintaining the axonemal ultrastructure and the assembly or stability of the outer dynein arms,thus expanding the phenotypic spectrum of CCDC34 missense mutations.
文摘Oxidative stress is one of the main mechanisms responsible for male infertility.Various conditions such as varicocele,obesity,advanced age,and lifestyle can lead to an increase in reactive oxygen species,causing an oxidative imbalance in the reproductiveenvironment.Spermatozoa are sensitive to reactive oxygen species and require energy to carry out their main function of fertilizingthe egg.Excessive reactive oxygen species can affect sperm metabolism,leading to immobility,impaired acrosome reaction,and celldeath,thereby impairing reproductive success.This double-blind randomized study evaluated the effect of supplementation withL-carnitine,acetyl-L-carnitine,vitamins,and other nutrients on semen quality in 104 infertile patients with or without varicocele,while also investigating the impact of factors such as obesity and advanced age on treatment.Sperm concentration significantlyincreased in the supplemented group compared to the placebo group(P=0.0186).Total sperm count also significantly increasedin the supplemented group(P=0.0117),as did sperm motility(P=0.0120).The treatment had a positive effect on patients upto 35 years of age in terms of sperm concentration(P=0.0352),while a body mass index(BMI)above 25 kg m^(−2) had a negativeeffect on sperm concentration(P=0.0110).Results were not showing a net benefit in stratifying patients in accordance withtheir BMI since sperm quality increase was not affected by this parameter.In conclusion,antioxidant supplementation may bebeneficial for infertile patients and has a more positive effect on younger patients with a normal weight.
文摘Glutathione peroxidase (GPx) is an antioxidant that plays an important role in the maintenance of male fertility. The aim of this study was to compare the profile of enzymatic activity of glutathione peroxidase in the seminal plasma of normozoosperm and those of pathological sperm. Thus, the activity of glutathione peroxidase was determined in the seminal plasma of 20 normozoosperms, 9 azoosperms and 31 oligoasthenoteratozoosperms. It was 37.58 ± 3.14 U/L in normozoosperms, 39.39 ± 2.27 U/L in oligoasthenoteratozoosperms, and 29.77 ± 2.62 U/L in azoosperms. The mean GPx enzyme activity of normozoosperms did not differ significantly from that of oligoasthenoteratozoosperms and azoosperms. In contrast, comparison of enzyme activity between abnormal sperms gave a significant difference. This study showed that glutathione peroxidase enzymatic activity is not related to sperm quality.
文摘Aims: To determine the impact of varicocele on the result of the spermogram in a group of hypo-fertile or infertile men. Patients and Method: This was a cross-sectional, descriptive study concerning 264 men collected between February 2020 and March 2022 at the Fertilia medical clinic in Bamako. The study population consisted of consenting male subjects presenting for infertility. All of our patients had already done a spermogram, they then benefited from a scrotal Doppler ultrasound. The scrotal echo-doppler was completed by an abdominal and pelvic echography in search of a possible etiology, in particular a renal cancer, a thrombosis of the renal or spermatic vein, a retroperitoneal mass or a nutcraker syndrome. Testicular volume was measured on ultrasound according to Lambert’s formula (length × width × height × 0.71). A volume = 16 ml was considered normal. Results: 264 patients were recruited in ours. The average age was 33 years with extremes ranging from 25 to 65 years. 149 patients or 56.44% were between 30 and 45 years old. 213 patients or 80.68% had primary infertility. All the patients, i.e. 100%, had a sperm anomaly and dilation of the pampiniform plexus veins. The most common sperm abnormalities were oligoasthenoteratozoospermia, which concerned 214 patients, or 81%, followed by azoospermia (40 patients, or 15%) and oligospermia (10 patients, or 4%). 213 patients or 80.68% had a Hirshen grade II varicocele, 45 patients or 17% had grade I and 06 patients or 2.27% had grade III. Among the 6 patients, 04 had left testicular atrophy and 2 bilateral atrophy. The venous reflux was more accentuated on the left than on the right. Conclusion: Varicocele is significantly found in men with infertility. Sperm alterations concern both the concentration of spermatozoa, their mobility and their vitality. Even if the mechanism of alteration of the sperm parameters is not well elucidated, our study made it possible to make the link between the dilation of the veins of the pampiniform plexus and the sperm abnormal
基金supported by the National Key Research and Developmental Program of China(2021YFC2700202,2022YFC2702601,2019YFA0802600,2022YFA0806303)National Natural Science Foundation of China(32470915,32000587,32270901,82171601)+1 种基金Global Select Project(DJK-LX-2022010)of the Institute of Health and Medicine,Hefei Comprehensive National Science Center,Joint Fund for New Medicine of USTC(YD9100002034)Scientific Research Foundation for Scholars of the First Affiliated Hospital of USTC(RC2023054)。
文摘Infertility represents a significant health concern,with sperm quantity and quality being crucial determinants of male fertility.Oligoasthenoteratozoospermia(OAT)is characterized by reduced sperm motility,lower sperm concentration,and morphological abnormalities in sperm heads and flagella.Although variants in several genes have been implicated in OAT,its genetic etiologies and pathogenetic mechanisms remain inadequately understood.In this study,we identified a homozygous nonsense mutation(c.916C>T,p.Arg306*)in the coiled-coil domain containing 146(CCDC146)gene in an infertile male patient with OAT.This mutation resulted in the production of a truncated CCDC146 protein(amino acids 1-305),retaining only two out of five coiled-coil domains.To validate the pathogenicity of the CCDC146 mutation,we generated a mouse model(Ccdc146^(mut/mut))with a similar mutation to that of the patient.Consistently,the Ccdc146mut/mut mice exhibited infertility,characterized by significantly reduced sperm counts,diminished motility,and multiple defects in sperm heads and flagella.Furthermore,the levels of axonemal proteins,including DNAH17,DNAH1,and SPAG6,were significantly reduced in the sperm of Ccdc146^(mut/mut) mice.Additionally,both human and mouse CCDC146 interacted with intraflagellar transport protein 20(IFT20),but this interaction was lost in the mutated versions,leading to the degradation of IFT20.This study identified a novel deleterious homozygous nonsense mutation in CCDC146 that causes male infertility,potentially by disrupting axonemal protein transportation.These findings offer valuable insights for genetic counseling and understanding the mechanisms underlying CCDC146 mutant-associated infertility in human males.
基金This study was supported by the National Key Research and Development Program of China(2021YFC2701400 and 2023YFC2705600)the National Natural Science Foundation of China(32288101,32100480,32370654,82271639,32322017,and32200485).
文摘Oligoasthenoteratozoospermia is an important factor affecting male fertility and has been found to be associated with genetic factors.However,there are stll a proportion of oligoasthenoteratozoospermia cases that cannot be explained by known pathogenic genetic variants.Here,we perform genetic analyses and identify bi-allelic loss-of-function variants of MFSD6L from an oligoasthenoteratozoospermia-affected family.Mfsd6l knock-out male mice also present male subfertility with reduced sperm concentration,motility,and deformed acrosomes.Further mechanistic analyses reveal that MFsD6L,as an acrosome membrane protein,plays an important role in the formation of acrosome by interacting with the inner acrosomal membrane protein SPACA1.Moreover,poor embryonic development is consistently observed after intracytoplasmic sperm injection treatment using spermatozoa from the MFSD6L-deficient man and male mice.Collectively,our findings reveal that MFSD6L is required for the anchoring of sperm acrosome and head shaping.The deficiency of MFsD6L affects male fertility and causes oligoasthenoter-atozoospermia in humans and mice.
文摘Intracytoplasmic sperm injection(ICSI)efficiently addresses male factor infertility.However,the occurrence of abnormal fertilization,mainly characterized by abnormal pronuclei(PN)patterns,merits investigation.To investigate abnormal fertilization patterns following ICSI and identify their respective associations with abnormal parameters in semen analysis(SA),a retrospective observational study including 1855 cycles was performed.Male infertility diagnosis relied on the 2010 WHO criteria.The population was divided into groups based on their SA results.The presence of 2PNs and extrusion of the second polar body(PB)indicated normal fertilization.A Kruskal–Wallis test along with a Wilcoxon post hoc evaluation and Bonferroni correction was employed for comparison among the groups.For the pregnancy rate,logistic regression was employed.No correlation was established between the SA abnormalities and the 1PN or 3PN formation rates.The highest and lowest 0PN rates were reported for the oligoasthenoteratozoospermic and normal groups,respectively.The lowest cleavage formation rates were identified in the oligoasthenozoospermic and oligoasthenoteratozoospermic groups.The aforementioned groups along with the oligoteratozoospermic group similarly presented the lowest blastocyst formation rates.For the clinical pregnancy rate,no statistically significant difference was observed.In conclusion,the incidence of two or more abnormal SA parameters–with the common denominator being oligozoospermia–may jeopardize normal fertilization,cleavage,and blastocyst rates.Once the developmental milestone of achieving blastocyst stage status was achieved,only oligoasthenozoospermia and oligoasthenoteratozoospermia were associated with lower rates.Interestingly,following adjustment for the number of blastocysts,no statistically significant differences were observed.
基金This study was supported by grants from the National Key Science Program S&T Program(2018YFC1004900 to YQT)the National Natural Science Foundation of China(81971447 to YQT)+1 种基金the Science and Technology Major Project of the Ministry of Science and Technology of Hunan Province(2017SK1030 to YQT)Graduate Research and Innovation Projects of Central South University(2019zzts734 to YL and 2019zzts322 to WLW)。
文摘Oligoasthenoteratozoospermia(OAT)refers to the combination of various sperm abnormalities,including a decreased sperm count,reduced motility,and abnormal sperm morphology.Only a few genetic causes have been shown to be associated with OAT.Herein,we identified a novel homozygous frameshift mutation in meiosis-specific nuclear structural 1(MNS1;NM_018365:c.603_604insG:p.Lys202Glufs*6)by whole-exome sequencing in an OAT proband from a consanguineous Chinese family.Subsequent variant screening identified four additional heterozygous MNS1 variants in 6/219 infertile individuals with oligoasthenospermia,but no MNS1 variants were observed among 223 fertile controls.Immunostaining analysis showed MNS1 to be normally located in the whole-sperm flagella,but was absent in the proband's sperm.Expression analysis by Western blot also confirmed that MNS1 was absent in the proband's sperm.Abnormal flagellum morphology and ultrastructural disturbances in outer doublet microtubules were observed in the proband's sperm.A total of three intracytoplasmic sperm injection cycles were carried out for the proband's wife,but they all failed to lead to a successful pregnancy.Overall,this is the first study to report a loss-of-function mutation in MNS1 causing OAT in a Han Chinese patient.
