Dkk3/REIC Deficiency Impairs Spermiation, Sperm Fibrous Sheath Integrity and the Sperm Motility of Mice

The role of <i>Dickkopf-3 (Dkk3)/REIC</i> (<i>The Reduced Expression in Immortalized Cells</i>), a Wnt-signaling inhibitor, in male reproductive physiology remains unknown thus far. To explore the functional details of <i>Dkk3/REIC</i> in the male reproductive pro...

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Main Authors: Ruizhi Xue, Wenfeng Lin, Hirofumi Fujita, Jingkai Sun, Rie Kinoshita, Kazuhiko Ochiai, Junichiro Futami, Masami Watanabe, Hideyo Ohuchi, Masakiyo Sakaguchi, Zhengyan Tang, Peng Huang, Yasutomo Nasu, Hiromi Kumon
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Language:English
Published: MDPI AG 2022-01-01
Series:Genes
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Online Access:https://www.mdpi.com/2073-4425/13/2/285
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author Ruizhi Xue
Wenfeng Lin
Hirofumi Fujita
Jingkai Sun
Rie Kinoshita
Kazuhiko Ochiai
Junichiro Futami
Masami Watanabe
Hideyo Ohuchi
Masakiyo Sakaguchi
Zhengyan Tang
Peng Huang
Yasutomo Nasu
Hiromi Kumon
author_facet Ruizhi Xue
Wenfeng Lin
Hirofumi Fujita
Jingkai Sun
Rie Kinoshita
Kazuhiko Ochiai
Junichiro Futami
Masami Watanabe
Hideyo Ohuchi
Masakiyo Sakaguchi
Zhengyan Tang
Peng Huang
Yasutomo Nasu
Hiromi Kumon
author_sort Ruizhi Xue
collection DOAJ
description The role of <i>Dickkopf-3 (Dkk3)/REIC</i> (<i>The Reduced Expression in Immortalized Cells</i>), a Wnt-signaling inhibitor, in male reproductive physiology remains unknown thus far. To explore the functional details of <i>Dkk3/REIC</i> in the male reproductive process, we studied the <i>Dkk3/REIC</i> knock-out (KO) mouse model. By examining testicular sections and investigating the sperm characteristics (count, vitality and motility) and ultrastructure, we compared the reproductive features between <i>Dkk3/REIC</i>-KO and wild-type (WT) male mice. To further explore the underlying molecular mechanism, we performed RNA sequencing (RNA-seq) analysis of testicular tissues. Our results showed that spermiation failure existed in seminiferous tubules of <i>Dkk3/REIC</i>-KO mice, and sperm from <i>Dkk3/REIC</i>-KO mice exhibited inferior motility (44.09 ± 8.12% vs. 23.26 ± 10.02%, <i>p</i> < 0.01). The Ultrastructure examination revealed defects in the sperm fibrous sheath of KO mice. Although the average count of <i>Dkk3/REIC</i>-KO epididymal sperm was less than that of the wild-types (9.30 ± 0.69 vs. 8.27 ± 0.87, ×10<sup>6</sup>), neither the gap (<i>p</i> > 0.05) nor the difference in the sperm vitality rate (72.83 ± 1.55% vs. 72.50 ± 0.71%, <i>p</i> > 0.05) were statistically significant. The RNA-seq and GO (Gene Oncology) enrichment results indicated that the differential genes were significantly enriched in the GO terms of cytoskeleton function, cAMP signaling and calcium ion binding. Collectively, our research demonstrates that <i>Dkk3/REIC</i> is involved in the process of spermiation, fibrous sheath integrity maintenance and sperm motility of mice.
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spelling doaj.art-b5cc07b06de54c64a992888e4b4d0ecd2023-11-23T20:04:29ZengMDPI AGGenes2073-44252022-01-0113228510.3390/genes13020285Dkk3/REIC Deficiency Impairs Spermiation, Sperm Fibrous Sheath Integrity and the Sperm Motility of MiceRuizhi Xue0Wenfeng Lin1Hirofumi Fujita2Jingkai Sun3Rie Kinoshita4Kazuhiko Ochiai5Junichiro Futami6Masami Watanabe7Hideyo Ohuchi8Masakiyo Sakaguchi9Zhengyan Tang10Peng Huang11Yasutomo Nasu12Hiromi Kumon13Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanLaboratory of Veterinary Hygiene, Nippon Veterinary and Life Science University, Tokyo 180-8602, JapanDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8530, JapanDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Urology, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanInnovation Center Okayama for Nanobio-Targeted Therapy, Okayama University, Okayama 700-8558, JapanThe role of <i>Dickkopf-3 (Dkk3)/REIC</i> (<i>The Reduced Expression in Immortalized Cells</i>), a Wnt-signaling inhibitor, in male reproductive physiology remains unknown thus far. To explore the functional details of <i>Dkk3/REIC</i> in the male reproductive process, we studied the <i>Dkk3/REIC</i> knock-out (KO) mouse model. By examining testicular sections and investigating the sperm characteristics (count, vitality and motility) and ultrastructure, we compared the reproductive features between <i>Dkk3/REIC</i>-KO and wild-type (WT) male mice. To further explore the underlying molecular mechanism, we performed RNA sequencing (RNA-seq) analysis of testicular tissues. Our results showed that spermiation failure existed in seminiferous tubules of <i>Dkk3/REIC</i>-KO mice, and sperm from <i>Dkk3/REIC</i>-KO mice exhibited inferior motility (44.09 ± 8.12% vs. 23.26 ± 10.02%, <i>p</i> < 0.01). The Ultrastructure examination revealed defects in the sperm fibrous sheath of KO mice. Although the average count of <i>Dkk3/REIC</i>-KO epididymal sperm was less than that of the wild-types (9.30 ± 0.69 vs. 8.27 ± 0.87, ×10<sup>6</sup>), neither the gap (<i>p</i> > 0.05) nor the difference in the sperm vitality rate (72.83 ± 1.55% vs. 72.50 ± 0.71%, <i>p</i> > 0.05) were statistically significant. The RNA-seq and GO (Gene Oncology) enrichment results indicated that the differential genes were significantly enriched in the GO terms of cytoskeleton function, cAMP signaling and calcium ion binding. Collectively, our research demonstrates that <i>Dkk3/REIC</i> is involved in the process of spermiation, fibrous sheath integrity maintenance and sperm motility of mice.https://www.mdpi.com/2073-4425/13/2/285<i>Dkk3/REIC</i>fibrous sheathknock-outRNA-seqspermiationsperm motility
spellingShingle Ruizhi Xue
Wenfeng Lin
Hirofumi Fujita
Jingkai Sun
Rie Kinoshita
Kazuhiko Ochiai
Junichiro Futami
Masami Watanabe
Hideyo Ohuchi
Masakiyo Sakaguchi
Zhengyan Tang
Peng Huang
Yasutomo Nasu
Hiromi Kumon
Dkk3/REIC Deficiency Impairs Spermiation, Sperm Fibrous Sheath Integrity and the Sperm Motility of Mice
Genes
<i>Dkk3/REIC</i>
fibrous sheath
knock-out
RNA-seq
spermiation
sperm motility
title Dkk3/REIC Deficiency Impairs Spermiation, Sperm Fibrous Sheath Integrity and the Sperm Motility of Mice
title_full Dkk3/REIC Deficiency Impairs Spermiation, Sperm Fibrous Sheath Integrity and the Sperm Motility of Mice
title_fullStr Dkk3/REIC Deficiency Impairs Spermiation, Sperm Fibrous Sheath Integrity and the Sperm Motility of Mice
title_full_unstemmed Dkk3/REIC Deficiency Impairs Spermiation, Sperm Fibrous Sheath Integrity and the Sperm Motility of Mice
title_short Dkk3/REIC Deficiency Impairs Spermiation, Sperm Fibrous Sheath Integrity and the Sperm Motility of Mice
title_sort dkk3 reic deficiency impairs spermiation sperm fibrous sheath integrity and the sperm motility of mice
topic <i>Dkk3/REIC</i>
fibrous sheath
knock-out
RNA-seq
spermiation
sperm motility
url https://www.mdpi.com/2073-4425/13/2/285
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