PMID- 35106541 OWN - NLM STAT- MEDLINE DCOM- 20220307 LR - 20230202 IS - 1945-7170 (Electronic) IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 163 IP - 4 DP - 2022 Apr 1 TI - PCP Protein Inversin Regulates Testis Function Through Changes in Cytoskeletal Organization of Actin and Microtubules. LID - 10.1210/endocr/bqac009 [doi] LID - bqac009 AB - Inversin is an integrated component of the Frizzled (Fzd)/Dishevelled (Dvl)/Diversin planar cell polarity (PCP) complex that is known to work in concert with the Van Gogh-like protein (eg, Vangl2)/Prickle PCP complex to support tissue and organ development including the brain, kidney, pancreas, and others. These PCP protein complexes are also recently shown to confer developing haploid spermatid PCP to support spermatogenesis in adult rat testes. However, with the exception of Dvl3 and Vangl2, other PCP proteins have not been investigated in the testis. Herein, we used the technique of RNA interference (RNAi) to examine the role of inversin (Invs) in Sertoli cell (SC) and testis function by corresponding studies in vitro and in vivo. When inversin was silenced by RNAi using specific small interfering RNA duplexes by transfecting primary cultures of SCs in vitro or testes in vivo, it was shown that inversin knockdown (KD) perturbed the SC tight junction-barrier function in vitro and in vivo using corresponding physiological and integrity assays. More important, inversin exerted its regulatory effects through changes in the organization of the actin and microtubule cytoskeletons, including reducing the ability of their polymerization. These changes, in turn, induced defects in spermatogenesis by loss of spermatid polarity, disruptive distribution of blood-testis barrier-associated proteins at the SC-cell interface, appearance of multinucleated round spermatids, and defects in the release of sperm at spermiation. CI - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Li, Linxi AU - Li L AUID- ORCID: 0000-0003-4021-4102 AD - The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. FAU - Gao, Sheng AU - Gao S AD - Institute of Reproductive Medicine, Nantong University School of Medicine, Nantong, Jiangsu 226001, China. FAU - Wang, Lingling AU - Wang L AD - Institute of Reproductive Medicine, Nantong University School of Medicine, Nantong, Jiangsu 226001, China. FAU - Bu, Tiao AU - Bu T AD - Institute of Reproductive Medicine, Nantong University School of Medicine, Nantong, Jiangsu 226001, China. FAU - Chu, Jinjin AU - Chu J AD - The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. FAU - Lv, Lixiu AU - Lv L AD - The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. FAU - Tahir, Anam AU - Tahir A AD - The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. FAU - Mao, Baiping AU - Mao B AD - The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. FAU - Li, Huitao AU - Li H AD - The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. FAU - Li, Xiaoheng AU - Li X AD - The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. FAU - Wang, Yiyan AU - Wang Y AD - The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. FAU - Wu, Xiaolong AU - Wu X AUID- ORCID: 0000-0003-3050-0324 AD - Institute of Reproductive Medicine, Nantong University School of Medicine, Nantong, Jiangsu 226001, China. FAU - Ge, Renshan AU - Ge R AD - The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. FAU - Cheng, C Yan AU - Cheng CY AUID- ORCID: 0000-0003-3117-3791 AD - The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. AD - Institute of Reproductive Medicine, Nantong University School of Medicine, Nantong, Jiangsu 226001, China. AD - Department of Urology and Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China. LA - eng GR - R01 HD056034/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (Actins) RN - 0 (Transcription Factors) SB - IM MH - Actins/*metabolism MH - Animals MH - Blood-Testis Barrier/metabolism MH - Cytoskeleton/*metabolism MH - Male MH - Microtubules/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Sertoli Cells/metabolism MH - Spermatids/metabolism MH - Spermatogenesis/physiology MH - Testis/*metabolism MH - Transcription Factors/*metabolism PMC - PMC8870424 OTO - NOTNLM OT - Sertoli cells OT - inversin OT - planar cell polarity OT - spermatogenesis OT - testis EDAT- 2022/02/03 06:00 MHDA- 2022/03/08 06:00 PMCR- 2023/02/01 CRDT- 2022/02/02 05:35 PHST- 2021/11/24 00:00 [received] PHST- 2022/02/03 06:00 [pubmed] PHST- 2022/03/08 06:00 [medline] PHST- 2022/02/02 05:35 [entrez] PHST- 2023/02/01 00:00 [pmc-release] AID - 6519617 [pii] AID - bqac009 [pii] AID - 10.1210/endocr/bqac009 [doi] PST - ppublish SO - Endocrinology. 2022 Apr 1;163(4):bqac009. doi: 10.1210/endocr/bqac009.