The essential role of intraflagellar transport protein IFT81 in male mice spermiogenesis and fertility.


  • 影响因子:3.35
  • DOI:10.1152/ajpcell.00450.2019
  • 作者列表:"Qu W","Yuan S","Quan C","Huang Q","Zhou Q","Yap Y","Shi L","Zhang D","Guest T","Li W","Yee SP","Zhang L","Cazin C","Hess RA","Ray PF","Kherraf ZE","Zhang Z
  • 发表时间:2020-06-01

:Intraflagellar transport (IFT) is an evolutionarily conserved mechanism that is indispensable for the formation and maintenance of cilia and flagella; however, the implications and functions of IFT81 remain unknown. In this study, we disrupted IFT81 expression in male germ cells starting from the spermatocyte stage. As a result, homozygous mutant males were completely infertile and displayed abnormal sperm parameters. In addition to oligozoospermia, spermatozoa presented dysmorphic and nonfunctional flagella. Histological examination of testes from homozygous mutant mice revealed abnormal spermiogenesis associated with sloughing of germ cells and the presence of numerous multinucleated giant germ cells (symblasts) in the lumen of seminiferous tubules and epididymis. Moreover, only few elongated spermatids and spermatozoa were seen in analyzed cross sections. Transmission electron microscopy showed a complete disorganization of the axoneme and para-axonemal structures such as the mitochondrial sheath, fibrous sheath, and outer dense fibers. In addition, numerous vesicles that contain unassembled microtubules were observed within developing spermatids. Acrosome structure analysis showed normal appearance, thus excluding a crucial role of IFT81 in acrosome biogenesis. These observations showed that IFT81 is an important member of the IFT process during spermatogenesis and that its absence is associated with abnormal flagellum formation leading to male infertility. The expression levels of several IFT components in testes, including IFT20, IFT25, IFT27, IFT57, IFT74, and IFT88, but not IFT140, were significantly reduced in homozygous mutant mice. Overall, our study demonstrates that IFT81 plays an essential role during spermatogenesis by modulating the assembly and elongation of the sperm flagella.


: 层内运输 (IFT) 是一种进化上保守的机制,对于纤毛和鞭毛的形成和维持是不可或缺的; 然而,IFT81的含义和功能仍然未知。在这项研究中,我们从精母细胞阶段开始破坏了IFT81在雄性生殖细胞中的表达。结果,纯合突变男性完全不育,并显示出异常的精子参数。除少精子症外,精子呈畸形和无功能性鞭毛。对纯合突变小鼠睾丸的组织学检查显示,精子生成异常与生殖细胞脱落有关,生精小管和附睾腔内存在大量多核巨生殖细胞 (幼细胞)。此外,在分析的横截面中仅观察到少数伸长的精子细胞和精子。透射电镜显示轴突和副轴突结构如线粒体鞘、纤维鞘和外致密纤维完全紊乱。此外,在发育中的精子细胞内观察到许多含有未组装的微管的囊泡。顶体结构分析显示外观正常,因此排除了IFT81在顶体生物发生中的关键作用。这些观察结果表明,IFT81是精子发生过程中IFT过程的重要成员,其缺失与导致男性不育的异常鞭毛形成有关。在纯合子突变小鼠中,睾丸中包括IFT20、IFT25、IFT27、IFT57、IFT74和IFT88但非IFT140的几种IFT组分的表达水平显著降低。总的来说,我们的研究表明IFT81通过调节精子鞭毛的组装和伸长在精子发生过程中起重要作用。



作者列表:["Hekim N","Gure MA","Metin Mahmutoglu A","Gunes S","Asci R","Henkel R"]

METHODS::1. Glutathione S-transferases (GST) and cytochrome P450s (CYPs) are xenobiotic metabolizing enzymes participating in the protection of cell. The present study aimed to investigate the relationship between polymorphisms of glutathione S-transferase M1 (GSTM1) null, glutathione S-transferase T1 (GSTT1) null, glutathione S-transferase P1 (GSTP1) Ile105Val, cytochrome P450 1A2 (CYP1A2) 734 C→A, cytochrome P450 2D6 (CYP2D6) 1934 G→A and male infertility.2. A total of 306 azoospermic or oligozoospermic infertile men and 129 normozoospermic or fertile controls were enrolled in the study. Multiplex polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism methods were used for genotyping. There was a significant relationship between male infertility and CYP2D6 GG genotype (p < 0.001). CYP1A2 AA genotype was slightly higher in the infertile group (p = 0.056).3. There was no association between GSTT1 null polymorphisms and male infertility (p = 0.068), GSTM1 null (p = 0.843) and GSTP1 Ile105Val (p = 0.192) genes. GSTM1 null genotype frequency was higher in azoospermic men (p = 0.009). Men carrying CYP1A2 AA genotype had higher risk of infertility risk (OR = 3.14; %95 CI = 1.16-8.54) in the smoker group.4. Our results demonstrated that polymorphisms of CYP2D6 and CYP1A2 may play a role in idiopathic male infertility in our sample population.

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作者列表:["Safaei Nezhad A","Ebrahimi L","Vakili MM","Kharaghani R"]

METHODS:PURPOSE:This study evaluated the effect of counseling based on the choice theory on irrational parenthood cognition (IPC)- and marital quality in infertile women. DESIGN AND METHODS:This randomized controlled trial was conducted on 50 primary infertile women in Zanjan, Iran. Stratified block randomization was used to allocate participants to groups. The intervention group received counseling, but the control group received routine care. Data were collected using the IPC and marital relationships quality based on the Glasser's choice theory. FINDINGS:A statistically significant difference was found between the groups in IPC (P = 0.005), but the difference in marital quality was not statically significant ( P = 0.085). PRACTICE IMPLICATIONS:Counseling can be used for decreasing IPC, but more interventions are needed to increase marital quality.

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作者列表:["Liu D","Yan J","Qiao J"]

METHODS::A decrease in cancer deaths has resulted in the possibility of child bearing for many young adult cancer survivors. Most antitumor treatment modalities are detrimental to female fertility, and methods for fertility preservation before gonadotoxic treatment, including cryopreservation of oocytes, embryos and ovarian tissue, have therefore been developed. This review focuses on the ovarian function of cancer patients, the safety and efficacy of fertility preservation methods, and the pregnancy outcomes of these patients. Breast cancer and hematological tumors constitute the majority of cancers in reproductive-aged female oncology patients. Ovarian function may not be impacted by breast cancer cells, while in patients with hematological malignancies, decreases in anti-Müllerian hormone and antral follicle counts have been demonstrated. In most cases, patients can undergo ovarian stimulation without delaying treatment, and a new stimulation protocol known as dual stimulation, which may be more efficient, has now been developed. Birth outcomes are also acceptable in cancer patients.

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