TY - JOUR
T1 - Dkk3/REIC Deficiency Impairs Spermiation, Sperm Fibrous Sheath Integrity and the Sperm Motility of Mice
AU - Xue, Ruizhi
AU - Lin, Wenfeng
AU - Fujita, Hirofumi
AU - Sun, Jingkai
AU - Kinoshita, Rie
AU - Ochiai, Kazuhiko
AU - Futami, Junichiro
AU - Watanabe, Masami
AU - Ohuchi, Hideyo
AU - Sakaguchi, Masakiyo
AU - Tang, Zhengyan
AU - Huang, Peng
AU - Nasu, Yasutomo
AU - Kumon, Hiromi
N1 - Funding Information:
This research was funded by the Ministry of Education, Culture, Sports, Science and Technology of Japan [grant No. 17K11138, 21K09371], the Project from National Health Commission of Hunan Province [grant No. B2019185] and the China Scholarship Council [grant No. 201906370192].
Funding Information:
Funding: This research was funded by the Ministry of Education, Culture, Sports, Science and Technology of Japan [grant No. 17K11138, 21K09371], the Project from National Health Commission of Hunan Province [grant No. B2019185] and the China Scholarship Council [grant No. 201906370192].
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/2
Y1 - 2022/2
N2 - The role of Dickkopf-3 (Dkk3)/REIC (The Reduced Expression in Immortalized Cells), a Wntsignaling inhibitor, in male reproductive physiology remains unknown thus far. To explore the functional details of Dkk3/REIC in the male reproductive process, we studied the Dkk3/REIC knockout (KO) mouse model. By examining testicular sections and investigating the sperm characteristics (count, vitality and motility) and ultrastructure, we compared the reproductive features between Dkk3/REIC-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 Dkk3/REIC-KO mice, and sperm from Dkk3/REIC-KO mice exhibited inferior motility (44.09 ± 8.12% vs. 23.26 ± 10.02%, p < 0.01). The Ultrastructure examination revealed defects in the sperm fibrous sheath of KO mice. Although the average count of Dkk3/REIC-KO epididymal sperm was less than that of the wild-types (9.30 ± 0.69 vs. 8.27 ± 0.87, ×106), neither the gap (p > 0.05) nor the difference in the sperm vitality rate (72.83 ± 1.55% vs. 72.50 ± 0.71%, p > 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 Dkk3/REIC is involved in the process of spermiation, fibrous sheath integrity maintenance and sperm motility of mice.
AB - The role of Dickkopf-3 (Dkk3)/REIC (The Reduced Expression in Immortalized Cells), a Wntsignaling inhibitor, in male reproductive physiology remains unknown thus far. To explore the functional details of Dkk3/REIC in the male reproductive process, we studied the Dkk3/REIC knockout (KO) mouse model. By examining testicular sections and investigating the sperm characteristics (count, vitality and motility) and ultrastructure, we compared the reproductive features between Dkk3/REIC-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 Dkk3/REIC-KO mice, and sperm from Dkk3/REIC-KO mice exhibited inferior motility (44.09 ± 8.12% vs. 23.26 ± 10.02%, p < 0.01). The Ultrastructure examination revealed defects in the sperm fibrous sheath of KO mice. Although the average count of Dkk3/REIC-KO epididymal sperm was less than that of the wild-types (9.30 ± 0.69 vs. 8.27 ± 0.87, ×106), neither the gap (p > 0.05) nor the difference in the sperm vitality rate (72.83 ± 1.55% vs. 72.50 ± 0.71%, p > 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 Dkk3/REIC is involved in the process of spermiation, fibrous sheath integrity maintenance and sperm motility of mice.
KW - Dkk3/REIC
KW - Fibrous sheath
KW - Knock-out
KW - RNA-seq
KW - Sperm motility
KW - Spermiation
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U2 - 10.3390/genes13020285
DO - 10.3390/genes13020285
M3 - Article
C2 - 35205329
AN - SCOPUS:85124082838
SN - 2073-4425
VL - 13
JO - Genes
JF - Genes
IS - 2
M1 - 285
ER -