PMID- 30387321 OWN - NLM STAT- MEDLINE DCOM- 20200415 LR - 20210109 IS - 1582-4934 (Electronic) IS - 1582-1838 (Print) IS - 1582-1838 (Linking) VI - 23 IP - 1 DP - 2019 Jan TI - Dynein axonemal intermediate chain 2 plays a role in gametogenesis by activation of Stat3. PG - 417-425 LID - 10.1111/jcmm.13945 [doi] AB - We previously identified the mouse dynein axonemal intermediate chain 2 (Dnaic2) gene. This gene expresses a component of the axonemal dynein complex that functions in cilia or flagella. We found that overexpression of Dnaic2 results in female subfertility and male infertility. In this study, we generated Dnaic2 knockdown (KD) mice and identified the potential regulatory mechanisms involved in Dnaic2 function. For phenotype analysis, we found that body weight was lighter and size was smaller in Dnaic2 KD mice than in wild-type mice. A total of 45% of these Dnaic2 KD mice were infertile due to sperm abnormalities in males, or had oocyte abnormalities and pathological changes in the tunica mucosa in the oviduct of females. Moreover, Dnaic2 overexpression enhanced the expression of proliferating cell nuclear antigen (PCNA) in the ovaries, which suggested that Dnaic2 stimulated proliferation of cells in the ovaries. However, PCNA expression in the testis of Dnaic2-overexpressed mice was lower than that in controls. Additionally, the ratio of Bax/B-cell lymphoma-2(Bcl-2) in the testis of Dnaic2-overexpressed mice was higher than that in controls, which suggested that Dnaic2 inhibited cellular proliferation in the testis. To examine the molecular action of Dnaic2, immunoprecipitation analysis was used and showed that Dnaic2 protein interacted with signal transducer and activator of transcription 3 (Stat3). Molecular modelling analysis showed that Dnaic2 bound with the linker and SH2 domains of Stat3. Furthermore, overexpression of Dnaic2 promoted phosphorylation of Stat3. In conclusion, our study suggests that Dnaic2 plays a role in oogenesis and spermatogenesis by activation of Stat3. CI - (c) 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. FAU - Yang, Zhaojuan AU - Yang Z AD - Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China. FAU - Xu, Bo AU - Xu B AD - Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China. FAU - Hu, Xiaopeng AU - Hu X AD - Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China. FAU - Yao, Xiaoying AU - Yao X AD - Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China. FAU - Tang, Yunhui AU - Tang Y AD - Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China. FAU - Qian, Cuifeng AU - Qian C AD - Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China. FAU - Wang, Shuzeng AU - Wang S AD - Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China. FAU - Chen, Haifeng AU - Chen H AD - School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. FAU - Bai, Xiaohui AU - Bai X AD - School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. FAU - Wu, Ji AU - Wu J AUID- ORCID: 0000-0002-6424-9783 AD - Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China. AD - Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, China. AD - Shanghai Key Laboratory of Reproductive Medicine, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181101 PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 RN - 0 (Dnaic2 protein, mouse) RN - 0 (STAT3 Transcription Factor) RN - 0 (Stat3 protein, mouse) RN - EC 3.6.4.2 (Axonemal Dyneins) SB - IM MH - Animals MH - Axonemal Dyneins/*metabolism MH - Cell Line MH - Cell Proliferation/physiology MH - Cilia/metabolism/physiology MH - Female MH - Gametogenesis/*physiology MH - HEK293 Cells MH - Humans MH - Infertility, Male/metabolism/physiopathology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - NIH 3T3 Cells MH - Ovary/metabolism/physiology MH - STAT3 Transcription Factor/*metabolism MH - Spermatogenesis/physiology MH - Testis/metabolism PMC - PMC6307815 OTO - NOTNLM OT - Dnaic2 OT - Stat3 OT - oogenesis OT - spermatogenesis EDAT- 2018/11/06 06:00 MHDA- 2020/04/16 06:00 PMCR- 2019/01/01 CRDT- 2018/11/03 06:00 PHST- 2018/07/09 00:00 [received] PHST- 2018/09/10 00:00 [accepted] PHST- 2018/11/06 06:00 [pubmed] PHST- 2020/04/16 06:00 [medline] PHST- 2018/11/03 06:00 [entrez] PHST- 2019/01/01 00:00 [pmc-release] AID - JCMM13945 [pii] AID - 10.1111/jcmm.13945 [doi] PST - ppublish SO - J Cell Mol Med. 2019 Jan;23(1):417-425. doi: 10.1111/jcmm.13945. Epub 2018 Nov 1.