Biallelic mutations in spermatogenesis and centriole-associated 1 like (SPATC1L) cause acephalic spermatozoa syndrome and male infertility / 亚洲男科学杂志(英文版)

Acephalic spermatozoa syndrome is a rare type of teratozoospermia that severely impairs the reproductive ability of male patients, and genetic defects have been recognized as the main cause of acephalic spermatozoa syndrome. Spermatogenesis and centriole-associated 1 like (SPATC1L) is indispensable for maintaining the integrity of sperm head-to-tail connections in mice, but its roles in human sperm and early embryonic development remain largely unknown. Herein, we conducted whole-exome sequencing (WES) of 22 infertile men with acephalic spermatozoa syndrome. An in silico analysis of the candidate variants was conducted, and WES data analysis was performed using another cohort consisting of 34 patients with acephalic spermatozoa syndrome and 25 control subjects with proven fertility. We identified biallelic mutations in SPATC1L (c.910C>T:p.Arg304Cys and c.994G>T:p.Glu332X) from a patient whose sperm displayed complete acephalia. Both SPATC1L variants are rare and deleterious. SPATC1L is mainly expressed at the head-tail junction of elongating spermatids. Plasmids containing pathogenic variants decreased the level of SPATC1L in vitro. Moreover, none of the patient's four attempts at intracytoplasmic sperm injection (ICSI) resulted in a transplantable embryo, which suggests that SPATC1L defects might affect early embryonic development. In conclusion, this study provides the first identification of SPATC1L as a novel gene for human acephalic spermatozoa syndrome. Furthermore, WES might be applied for patients with acephalic spermatozoa syndrome who exhibit reiterative ICSI failures.

Neuronal plasticity of otolith-related vestibular system / 中国医学科学院学报

This review focuses on our effort in addressing the development and lesion-induced plasticity of the gravity sensing system. After severance of sensory input from one inner ear, there is a bilateral imbalance in response dynamics and spatial coding behavior between neuronal subpopulations on the two sides. These data provide the basis for deranged spatial coding and motor deficits accompanying unilateral labyrinthectomy. Recent studies have also confirmed that both glutamate receptors and neurotrophin receptors within the bilateral vestibular nuclei are implicated in the plasticity during vestibular compensation and development. Changes in plasticity not only provide insight into the formation of a spatial map and recovery of vestibular function but also on the design of drugs for therapeutic strategies applicable to infants or vestibular disorders such as vertigo and dizziness.

Localization of vesicular glutamate transporters in the peripheral vestibular system of rat / 神经科学通报·英文版

<p><b>OBJECTIVE</b>To examine the vesicular glutamate transporters (VGluTs: VGluT1-VGluT3) in the peripheral vestibular system.</p><p><b>METHODS</b>The vestibular structures, including Scarpa's ganglion (vestibular ganglion, VG), maculae of utricle and saccule, and ampullary cristae, from normal Sprague-Dawley rats were processed immunohistochemically for VGluTs, by avidin-biotinylated peroxidase complex method, with 3-3'-diaminobenzidine (DAB) as chromogen.</p><p><b>RESULTS</b>(1) VGluT1 was localized to partial neurons of VG and to the putative primary afferent fibers innervating vestibular end-organs. (2) Intense VGluT3 immunoreactivity was detected in large number of sensory epithelia cells, and weak labeling of VGluT3-positive afferent fibers was in the maculae and ampullary cristae. (3) No or very weak VGluT2 immunoreactivity was observed in the VG and acoustic maculae.</p><p><b>CONCLUSION</b>These results provide the morphological support that glutamate exists in the peripheral vestibular system, and it may play an important role in the centripetal vestibular transmission.</p>

Vesicular glutamate transporter-immunoreactivities in the vestibular nuclear complex of rat / 神经科学通报·英文版

Objective Aims to delineate the distribution profile of three isoforms of vesicular glutamate transporter (VGluT), viz. VGluT1-3, and their cellular localization within vestibular nuclear complex (VNC). Methods Brain sections from normal Sprague-Dawley rats were processed immunohistochemically for VGluT detection, employing avidin-biotinylated peroxidase complex method with 3-3'-diaminobenzidine (DAB) as chromogen. Results The whole VNC expressed all of the three transporters that were observed to be localized to the fiber endings. Compared with VGluT1 and VGluT3, VGluT2 demonstrated a relatively homogeneous distribution, with much higher density in VNC. VGluT3 displayed the highest density in lateral vestibular nucleus and group X, contrasting with the sparse immunostained puncta within vestibular medial and inferior nuclei. Conclusion Glutamtatergic pathways participate in the processing of vestibular signals within VNC mainly through the re-uptake of glutamate into synaptic vesicles by VGluT1 and 2, whereas VGluT3 may play a similar role mainly in areas other than medial and inferior nuclei of VNC.