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.

The role of tyrosine phosphatase Shp2 in spermatogonial differentiation and spermatocyte meiosis / 亚洲男科学杂志(英文版)

The transition from spermatogonia to spermatocytes and the initiation of meiosis are key steps in spermatogenesis and are precisely regulated by a plethora of proteins. However, the underlying molecular mechanism remains largely unknown. Here, we report that Src homology domain tyrosine phosphatase 2 (Shp2; encoded by the protein tyrosine phosphatase, nonreceptor type 11 [Ptpn11] gene) is abundant in spermatogonia but markedly decreases in meiotic spermatocytes. Conditional knockout of Shp2 in spermatogonia in mice using stimulated by retinoic acid gene 8 (Stra8)-cre enhanced spermatogonial differentiation and disturbed the meiotic process. Depletion of Shp2 in spermatogonia caused many meiotic spermatocytes to die; moreover, the surviving spermatocytes reached the leptotene stage early at postnatal day 9 (PN9) and the pachytene stage at PN11-13. In preleptotene spermatocytes, Shp2 deletion disrupted the expression of meiotic genes, such as disrupted meiotic cDNA 1 (Dmc1), DNA repair recombinase rad51 (Rad51), and structural maintenance of chromosome 3 (Smc3), and these deficiencies interrupted spermatocyte meiosis. In GC-1 cells cultured in vitro, Shp2 knockdown suppressed the retinoic acid (RA)-induced phosphorylation of extracellular-regulated protein kinase (Erk) and protein kinase B (Akt/PKB) and the expression of target genes such as synaptonemal complex protein 3 (Sycp3) and Dmc1. Together, these data suggest that Shp2 plays a crucial role in spermatogenesis by governing the transition from spermatogonia to spermatocytes and by mediating meiotic progression through regulating gene transcription, thus providing a potential treatment target for male infertility.

Changes in Endosymbiotic Bacteria of Brown Planthoppers During the Process of Adaptation to Different Resistant Rice Varieties.

The specific primers of five species of endosymbiotic bacteria were designed to determine their numbers in three virulent populations of brown planthopper, Nilapavata lugens Stål, and to assess changes during adaptation to different resistant varieties using fluorescent quantitative PCR. The results showed that Chryseobacterium was the dominant bacteria in all three populations of brown planthopper, followed by Acinetobacter in TN1 population, Arsenophonus and Serratia in Mudgo population, and Arthrobacter and Acinetobacter in ASD7 population. When the TN1 population of brown planthopper was transferred to ASD7 (with resistant gene bph2) rice plants, Chryseobacterium was still the dominant bacteria, but the originally subdominant Acinetobacter declined to a level that was not significantly different from that of other endosymbiotic bacteria. After they were transferred to Mudgo (with resistant gene Bph1), Serratia and Arsenophonus increased significantly and became the dominant bacteria. However, they declined to a level that was not significantly different from that of the three other species after two generations. When ASD7 and Mudgo populations of brown planthopper were transferred to the susceptible variety TN1, the community of endosymbiotic bacteria in the ASD7 population of brown planthopper showed no significant changes. However, the numbers of Acinetobacter and Arthrobacter in the Mudgo population of brown planthopper exhibited a transient increase and returned to their original levels after two generations. After the Mudgo population of brown planthopper was transferred to ASD7 rice plants, the quantity of endosymbiotic bacteria fluctuated, but the bacterial structure did not change significantly. However, after the ASD7 population of brown planthopper was transferred to the Mudgo rice plants, the bacterial structure changed significantly. Serratia and Arsenophonus increased significantly and became dominant. Although Serratia and Arsenophonus decreased significantly after a generation, they were still greater than Chryseobacterium. It was presumed that Chryseobacterium was dominant in all three populations of virulent brown planthoppers, but had no significant effect on virulence variation of brown planthopper. However, Serratia and Arsenophonus might be correlated with virulence variation of brown planthopper.