SEPT12 gene mutation leads to asthenospermia and male infertility
10.19405/j.cnki.issn1000-1492.2024.06.003
- Author:
Senzhao Guo
1
,
2
;
Hui Yu
1
,
2
;
Meng Gu
1
,
2
;
Baoyan Wu
1
,
2
;
Kuokuo Li
1
,
2
;
Dongdong Tang
1
,
2
;
Xiaojin He
1
,
2
;
Yunxia Cao
1
,
2
;
Mingrong Lv
1
,
2
Author Information
1. Dept of Obstetrics and Gynecology, The First Afiliated Hospital of Anhui Medical University, Hefei 230032
2. National Health and Wellness Commission Key Laboratory of Gametes and Genital Tract Anomalies Research , Hefei 230032
- Publication Type:Journal Article
- Keywords:
male infertility;
asthenoteratozoospermia;
SEPT12;
whole exome sequencing
- From:
Acta Universitatis Medicinalis Anhui
2024;59(6):939-946
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To investigate the role of member septin family (SEPT12)in human spermatogenesis and its influence on sperm motility and sperm ultrastructure.
Methods :Whole exome sequencing (WES) was performed on peripheral blood DNA extracted from 375 patients with asthenoteratozoospermia , and a patient with idiopathic infertility carrying compound heterozygous mutation of SEPT12 was screened out. Sanger sequencing was performed to verify the mutation , and co⁃segregation analysis was performed in the family. The morphological abnormalities of sperm were analyzed by hematoxylin⁃eosin (HE) staining and scanning electron microscopy (SEM) , and the ultrastructural defects of sperm were analyzed by transmission electron microscopy (TEM) . Then the effects of the mutation on the level and position of the protein and the changes of the location and level of the defect structure markers were analyzed by Western blot and immune⁃fluorescence (IF) .
Results :The compound heterozygous mutations c.C332A (p. T111K) and c. 406_416 del TGCTCGTATTG (p. q136 VFS ∗39) in the SEPT12 gene were screened and identified in a patient with asthenoteratozoospermia. The mutations were verified by Sanger sequencing , which was consistent with the co⁃segregation genetic pattern of the family. The mutations resulted in loss of protein expression , decreased sperm motility and sperm morphological deformities , mainly including short tail , curly tail and irregular sperm head. The ultrastructure of sperm showed that the annulus between the mid⁃piece and the principlepiece was missing , the acrosome membrane of sperm head fell off and the nucleus contained vacuoles. In the midpiece of sperm flagella , the arrangement of mitochondrial sheath was disordered , most of flagella axoneme central pair was absent , microtubules doublet was missing or disordered , and some radical spoke was absent. By Western blot and IF , the marker proteins of related structural components were detected , and the results showed that the level of SEPT4 protein decreased , SEPT6 protein unchanged , acrosomal related proteins ACTL7A and ACROSIN protein missing , and the expression levels of mitochondrial and axoneme related proteins TOMM20 , SPAG6 and RSPH3 protein significantly decreased.
Conclusion :The deletion of SEPT12 protein caused by SEPT12 gene mutation leads to the deletion of the annulus between the mid⁃piece and the principle⁃piece , and the abnormal assembly of sperm acrosome , mitochondrial sheath and flagella.
- Full text:2024081420255182238SEPT12基因突变导致弱畸精子症引起男性不育_郭森朝.pdf
