FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4310264110> ?p ?o ?g. }

• W4310264110 abstract "Abstract STUDY QUESTION Is Tcte1 mutation causative for male infertility? SUMMARY ANSWER Collected data underline the complex and devastating effect of the single-gene mutation on testicular molecular network, leading to male reproductive failure. WHAT IS KNOWN ALREADY Latest data revealed mutations in genes related to axonemal dynein arms as causative for morphology and motility abnormalities in spermatozoa of infertile males, including dysplasia of fibrous sheath (DFS) and multiple morphological abnormalities in the sperm flagella (MMAF). The nexin-dynein regulatory complex (N-DRC) coordinates the dynein arm activity, and is built from DRC1-DRC7 proteins. DRC5 (TCTE1) – one of N-DRC element, has been already reported as a candidate for abnormal sperm flagella beating, however, only in restricted manner with no clear explanation of respective observations. STUDY DESIGN, SIZE, DURATION Using CRISPR/Cas9 genome editing technique, mouse knockout line of Tcte1 gene was created on the basis of C57Bl/6J strain. Then, the mouse reproductive potential, semen characteristics, testicular gene expression level, sperm ATP and testis apoptosis level measurements have been performed, followed by visualization of N-DRC proteins in sperm, and protein modeling in silico . Also, a pilot genomic sequencing study of samples from human infertile males (n=248) was applied for screening of TCTE1 variants. PARTICIPANTS/MATERIALS, SETTING, METHODS To check the reproductive potential of KO mice, adult animals were crossed for delivery of three litters per caged pair, but no longer than for 6 months, in various combinations of zygosity. All experiments were performed for wild type (WT – control group), heterozygous Tcte1 +/− , and homozygous Tcte1 −/− male mice. Gross anatomy was performed on testis and epididymis, followed by semen analysis. Sequencing of RNA (RNAseq; Illumina) has been done for mice testis tissues. STRING interactions have been checked for protein-protein interactions, based on changed expression level of corresponding genes identified in the mouse testis RNAseq experiments. Immunofluorescence in situ staining was performed to detect the N-DRC complex proteins: Tcte1 (Drc5), Drc7, Fbxl13 (Drc6), and Eps8l1 (Drc3) in mouse spermatozoa. To determine the ATP amount in spermatozoa, the luminescence level was measured. Also, immunofluorescent in situ staining was performed to check the level of apoptosis via caspase 3 visualization on mouse testis samples. DNA from whole blood samples of infertile males (n=137 non-obstructive azoospermia or cryptozoospermia, n=111 samples with spectrum of oligoasthenoteratozoospermia, including n=47 with asthenozoospermia) has been extracted to perform genomic sequencing (WGS, WES or Sanger). Protein prediction modeling of human identified variants and the exon 3 structure deleted in mouse knockout has been also performed. MAIN RESULTS AND THE ROLE OF CHANCE No progeny at all was found for homozygous males with revealed oligoasthenoteratozoospermia, while heterozygous animals (fertile) manifested oligozoospermia, suggesting haploinsufficiency. RNA-sequencing of the testicular tissue showed the influence of Tcte1 mutations on the expression pattern of 21 genes responsible for mitochondrial ATP processing, linked with apoptosis, or spermatogenesis. In Tcte1 −/− males the protein revealed only residual amounts in sperm head nucleus, and was not transported to sperm flagella, as other N-DRC components. Decreased ATP level (2.4-fold lower) was found in spermatozoa of homozygous mice, together with disturbed tail:midpiece ratio, leading to abnormal sperm tail beating. Casp3-positive signals (indicating apoptosis) were observed in spermatogonia only, at similar level in all three mouse genotypes. Mutation screening of human infertile males revealed 1 novel and 5 ultrarare heterogeneous variants (predicted as disease causing) in 6.05% of patients studied. Protein prediction modeling of identified variants revealed changes in the protein surface charge potential, leading to disruption in helix flexibility or its dynamics, thus, suggesting the disrupted TCTE1 interaction with its binding partners located within the axoneme." @default.
• W4310264110 created "2022-11-30" @default.
• W4310264110 creator A5023795089 @default.
• W4310264110 creator A5027324063 @default.
• W4310264110 creator A5031104979 @default.
• W4310264110 creator A5040047607 @default.
• W4310264110 creator A5048151028 @default.
• W4310264110 creator A5052710276 @default.
• W4310264110 creator A5053383712 @default.
• W4310264110 creator A5060184451 @default.
• W4310264110 creator A5061522801 @default.
• W4310264110 creator A5065661122 @default.
• W4310264110 creator A5067786510 @default.
• W4310264110 date "2022-11-25" @default.
• W4310264110 modified "2023-10-16" @default.
• W4310264110 title "<i>Tcte1</i>knockout influence on energy chain transportation, apoptosis and spermatogenesis – implications for male infertility" @default.
• W4310264110 cites W1502562917 @default.
• W4310264110 cites W1555768307 @default.
• W4310264110 cites W1579924187 @default.
• W4310264110 cites W1730440878 @default.
• W4310264110 cites W1803102843 @default.
• W4310264110 cites W1874377842 @default.
• W4310264110 cites W1969127101 @default.
• W4310264110 cites W1970501568 @default.
• W4310264110 cites W1973632178 @default.
• W4310264110 cites W1981045929 @default.
• W4310264110 cites W1987134040 @default.
• W4310264110 cites W1988089345 @default.
• W4310264110 cites W1992323427 @default.
• W4310264110 cites W1994605453 @default.
• W4310264110 cites W2002376660 @default.
• W4310264110 cites W2013799999 @default.
• W4310264110 cites W2014213609 @default.
• W4310264110 cites W2037312364 @default.
• W4310264110 cites W2047481197 @default.
• W4310264110 cites W2051978340 @default.
• W4310264110 cites W2075529993 @default.
• W4310264110 cites W2082248345 @default.
• W4310264110 cites W2088115212 @default.
• W4310264110 cites W2088290371 @default.
• W4310264110 cites W2088819598 @default.
• W4310264110 cites W2094458603 @default.
• W4310264110 cites W2108999119 @default.
• W4310264110 cites W2118233937 @default.
• W4310264110 cites W2122603396 @default.
• W4310264110 cites W2122896661 @default.
• W4310264110 cites W2123500593 @default.
• W4310264110 cites W2124026197 @default.
• W4310264110 cites W2125850072 @default.
• W4310264110 cites W2126451116 @default.
• W4310264110 cites W2130814155 @default.
• W4310264110 cites W2144998676 @default.
• W4310264110 cites W2148748454 @default.
• W4310264110 cites W2152956782 @default.
• W4310264110 cites W2263101679 @default.
• W4310264110 cites W2298446724 @default.
• W4310264110 cites W2325121937 @default.
• W4310264110 cites W2326112268 @default.
• W4310264110 cites W2417483443 @default.
• W4310264110 cites W2473351708 @default.
• W4310264110 cites W2484590415 @default.
• W4310264110 cites W2498082946 @default.
• W4310264110 cites W2515630929 @default.
• W4310264110 cites W2521967673 @default.
• W4310264110 cites W2545963653 @default.
• W4310264110 cites W2555800265 @default.
• W4310264110 cites W2591563147 @default.
• W4310264110 cites W2611030203 @default.
• W4310264110 cites W2617453476 @default.
• W4310264110 cites W2620185811 @default.
• W4310264110 cites W2654333968 @default.
• W4310264110 cites W2667603345 @default.
• W4310264110 cites W2736831818 @default.
• W4310264110 cites W2743747099 @default.
• W4310264110 cites W2762968408 @default.
• W4310264110 cites W2766802654 @default.
• W4310264110 cites W2768294698 @default.
• W4310264110 cites W2770976914 @default.
• W4310264110 cites W2781818691 @default.
• W4310264110 cites W2784187266 @default.
• W4310264110 cites W2789804657 @default.
• W4310264110 cites W2790887288 @default.
• W4310264110 cites W2806611600 @default.
• W4310264110 cites W2900569176 @default.
• W4310264110 cites W2901634281 @default.
• W4310264110 cites W2903902122 @default.
• W4310264110 cites W2906063165 @default.
• W4310264110 cites W2914553708 @default.
• W4310264110 cites W2914997541 @default.
• W4310264110 cites W2929590081 @default.
• W4310264110 cites W2951501862 @default.
• W4310264110 cites W2967730711 @default.
• W4310264110 cites W2969453130 @default.
• W4310264110 cites W2979535373 @default.
• W4310264110 cites W2982503296 @default.
• W4310264110 cites W2989859078 @default.
• W4310264110 cites W3000595084 @default.
• W4310264110 cites W3002838491 @default.
• W4310264110 cites W3013139790 @default.
• W4310264110 cites W3015870595 @default.

• next