PMID- 31134714 OWN - NLM STAT- MEDLINE DCOM- 20200618 LR - 20200618 IS - 1098-2795 (Electronic) IS - 1040-452X (Linking) VI - 86 IP - 8 DP - 2019 Aug TI - Functional importance of palmitoyl protein thioesterase 1 (PPT1) expression by Sertoli cells in mediating cholesterol metabolism and maintenance of sperm quality. PG - 984-998 LID - 10.1002/mrd.23173 [doi] AB - Sertoli cells are a type of nurse cell in the seminiferous epithelium that are crucial for sustaining spermatogenesis by extending nutritional and energy support to the developing germ cells. Dysfunction of Sertoli cells could cause disordered spermatogenesis and reduced fertility in males. In this study, we focused on the expression and function of palmitoyl protein thioesterase 1 (PPT1), a lysosomal depalmitoylating enzyme, in Sertoli cells. Here, we show that PPT1 expression in Sertoli cells is responsive to cholesterol treatment and that specific knockout of Ppt1 in Sertoli cells causes male subfertility associated with poor sperm quality and a high ratio of sperm deformity. Specifically, Ppt1 deficiency leads to poor cell variably accompanied with abnormal lysosome accumulation and increased cholesterol levels in Sertoli cells. Further, Ppt1 deficiency results in poor adhesion of developing germ cells to Sertoli cells in the seminiferous epithelium, which is likely to be responsible for the reduced male fertility as a consequence of declines in sperm count and motility as well as a high incidence of sperm head deformity. In summary, PPT1 affects sperm quality and male fertility through regulating lysosomal function and cholesterol metabolism in Sertoli cells. CI - (c) 2019 Wiley Periodicals, Inc. FAU - Zhao, Wenzhen AU - Zhao W AD - Department of Histology and Embryology, School of Basic Medical Science, Dali University, Yunnan, China. AD - Institute of Reproductive Medicine, Dali University, Yunnan, China. FAU - Su, Juan AU - Su J AD - Department of Physiology and Pathophysiology, School of Basic Medical Science, Dali University, Yunnan, China. FAU - Wang, Yuntao AU - Wang Y AD - Department of Histology and Embryology, School of Basic Medical Science, Dali University, Yunnan, China. FAU - Qian, Tijun AU - Qian T AD - Vector Laboratory, Institute of Pathogens and Vectors, Dali University, Yunnan, China. FAU - Liu, Yue AU - Liu Y AUID- ORCID: 0000-0002-2700-922X AD - Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190527 PL - United States TA - Mol Reprod Dev JT - Molecular reproduction and development JID - 8903333 RN - 97C5T2UQ7J (Cholesterol) RN - EC 3.1.2.- (Thiolester Hydrolases) RN - EC 3.1.2.22 (palmitoyl-protein thioesterase) SB - IM MH - Animals MH - Cholesterol/*metabolism MH - *Fertility MH - *Gene Expression Regulation, Enzymologic MH - Male MH - Mice MH - Seminiferous Tubules/cytology/enzymology MH - Sertoli Cells/cytology/*enzymology MH - Sperm Count MH - Spermatozoa/cytology/*enzymology MH - Thiolester Hydrolases/*biosynthesis OTO - NOTNLM OT - PPT1 OT - Sertoli cell OT - cholesterol metabolism OT - lysosome OT - sperm quality EDAT- 2019/05/28 06:00 MHDA- 2020/06/19 06:00 CRDT- 2019/05/29 06:00 PHST- 2018/12/10 00:00 [received] PHST- 2019/04/23 00:00 [revised] PHST- 2019/05/01 00:00 [accepted] PHST- 2019/05/28 06:00 [pubmed] PHST- 2020/06/19 06:00 [medline] PHST- 2019/05/29 06:00 [entrez] AID - 10.1002/mrd.23173 [doi] PST - ppublish SO - Mol Reprod Dev. 2019 Aug;86(8):984-998. doi: 10.1002/mrd.23173. Epub 2019 May 27.