Deficiency of the <i>Tmem232</i> Gene Causes Male Infertility with Morphological Abnormalities of the Sperm Flagellum in Mice

The axoneme and accessory structures of flagella are critical for sperm motility and male fertilization. Sperm production needs precise and highly ordered gene expression to initiate and sustain the many cellular processes that result in mature spermatozoa. Here, we identified a testis enriched gene...

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Main Authors: Xiuqing He, Wenyu Mu, Ziqi Wang, Ke Xu, Yingying Yin, Gang Lu, Wai-Yee Chan, Hongbin Liu, Yue Lv, Shangming Liu
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/12/12/1614
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author Xiuqing He
Wenyu Mu
Ziqi Wang
Ke Xu
Yingying Yin
Gang Lu
Wai-Yee Chan
Hongbin Liu
Yue Lv
Shangming Liu
author_facet Xiuqing He
Wenyu Mu
Ziqi Wang
Ke Xu
Yingying Yin
Gang Lu
Wai-Yee Chan
Hongbin Liu
Yue Lv
Shangming Liu
author_sort Xiuqing He
collection DOAJ
description The axoneme and accessory structures of flagella are critical for sperm motility and male fertilization. Sperm production needs precise and highly ordered gene expression to initiate and sustain the many cellular processes that result in mature spermatozoa. Here, we identified a testis enriched gene transmembrane protein 232 (<i>Tmem232</i>), which is essential for the structural integrity of the spermatozoa flagella axoneme. <i>Tmem232</i> knockout mice were generated for in vivo analyses of its functions in spermatogenesis. Phenotypic analysis showed that deletion of <i>Tmem232</i> in mice causes male-specific infertility. Transmission electron microscopy together with scanning electron microscopy were applied to analyze the spermatozoa flagella and it was observed that the lack of TMEM232 caused failure of the cytoplasm removal and the absence of the 7th outer microtubule doublet with its corresponding outer dense fiber (ODF). Co-IP assays further identified that TMEM232 interacts with ODF family protein ODF1, which is essential to maintain sperm motility. In conclusion, our findings indicate that TMEM232 is a critical protein for male fertility and sperm motility by regulating sperm cytoplasm removal and maintaining axoneme integrity.
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spelling doaj.art-7d449684d8964442a2bd653f7669dfa92023-11-18T09:43:28ZengMDPI AGCells2073-44092023-06-011212161410.3390/cells12121614Deficiency of the <i>Tmem232</i> Gene Causes Male Infertility with Morphological Abnormalities of the Sperm Flagellum in MiceXiuqing He0Wenyu Mu1Ziqi Wang2Ke Xu3Yingying Yin4Gang Lu5Wai-Yee Chan6Hongbin Liu7Yue Lv8Shangming Liu9School of Basic Medical Sciences, Shandong University, Jinan 250012, ChinaCenter for Reproductive Medicine, Shandong University, Jinan 250012, ChinaCenter for Reproductive Medicine, Shandong University, Jinan 250012, ChinaCenter for Reproductive Medicine, Shandong University, Jinan 250012, ChinaCenter for Reproductive Medicine, Shandong University, Jinan 250012, ChinaCUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaCUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaCenter for Reproductive Medicine, Shandong University, Jinan 250012, ChinaCUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaSchool of Basic Medical Sciences, Shandong University, Jinan 250012, ChinaThe axoneme and accessory structures of flagella are critical for sperm motility and male fertilization. Sperm production needs precise and highly ordered gene expression to initiate and sustain the many cellular processes that result in mature spermatozoa. Here, we identified a testis enriched gene transmembrane protein 232 (<i>Tmem232</i>), which is essential for the structural integrity of the spermatozoa flagella axoneme. <i>Tmem232</i> knockout mice were generated for in vivo analyses of its functions in spermatogenesis. Phenotypic analysis showed that deletion of <i>Tmem232</i> in mice causes male-specific infertility. Transmission electron microscopy together with scanning electron microscopy were applied to analyze the spermatozoa flagella and it was observed that the lack of TMEM232 caused failure of the cytoplasm removal and the absence of the 7th outer microtubule doublet with its corresponding outer dense fiber (ODF). Co-IP assays further identified that TMEM232 interacts with ODF family protein ODF1, which is essential to maintain sperm motility. In conclusion, our findings indicate that TMEM232 is a critical protein for male fertility and sperm motility by regulating sperm cytoplasm removal and maintaining axoneme integrity.https://www.mdpi.com/2073-4409/12/12/1614TMEM232ODF1spermaxonemecytoplasm removal
spellingShingle Xiuqing He
Wenyu Mu
Ziqi Wang
Ke Xu
Yingying Yin
Gang Lu
Wai-Yee Chan
Hongbin Liu
Yue Lv
Shangming Liu
Deficiency of the <i>Tmem232</i> Gene Causes Male Infertility with Morphological Abnormalities of the Sperm Flagellum in Mice
Cells
TMEM232
ODF1
sperm
axoneme
cytoplasm removal
title Deficiency of the <i>Tmem232</i> Gene Causes Male Infertility with Morphological Abnormalities of the Sperm Flagellum in Mice
title_full Deficiency of the <i>Tmem232</i> Gene Causes Male Infertility with Morphological Abnormalities of the Sperm Flagellum in Mice
title_fullStr Deficiency of the <i>Tmem232</i> Gene Causes Male Infertility with Morphological Abnormalities of the Sperm Flagellum in Mice
title_full_unstemmed Deficiency of the <i>Tmem232</i> Gene Causes Male Infertility with Morphological Abnormalities of the Sperm Flagellum in Mice
title_short Deficiency of the <i>Tmem232</i> Gene Causes Male Infertility with Morphological Abnormalities of the Sperm Flagellum in Mice
title_sort deficiency of the i tmem232 i gene causes male infertility with morphological abnormalities of the sperm flagellum in mice
topic TMEM232
ODF1
sperm
axoneme
cytoplasm removal
url https://www.mdpi.com/2073-4409/12/12/1614
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