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Existence and distribution of Niemann–Pick type 2C (NPC2) in prawn reproductive tract and its putative role as a cholesterol modulator during sperm transit in the vas deferens

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Abstract

Sequestering of cholesterol (CHO) is a hallmark molecular event that is known to be associated with sperm gaining their fertilizing ability in a broad array of animals. We have shown previously that the level of CHO declines in the Macrobrachium rosenbergii sperm membrane when they are migrating into the vas deferens, prompting us to search for CHO transporters, one of which is Niemann–Pick type 2C (NPC2), within the prawn male reproductive tract. Sequence comparison of MrNPC2 with other NPC2, from crustaceans to mammals, revealed its conserved features in the hydrophobic cavity with 3 amino acids forming a CHO lid that is identical in all species analyzed. Expressions of MrNPC2 transcript and protein were detected in testicular supporting and interstitial cells and along the epithelial cells of the vas deferens. As confirmed by live cell staining, the testicular sperm (Tsp) surface was devoid of MrNPC2 but it first existed on the vas deferens sperm, suggesting its acquisition from the luminal fluid, possibly through trafficking of multi-lamellar vesicles during sperm transit in the vas deferens. We further showed that recombinant MrNPC2 had a high affinity towards CHO in the lipid extracts, either from Tsp or from lipid vesicles in the vas deferens. Together, our results indicated the presence of MrNPC2 in the male reproductive tract, which may play an important role as a CHO modulator between the sperm membrane and vas deferens epithelial communication.

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References

  • Alfaro J, Ulate K, Vargas M (2007) Sperm maturation and capacitation in the open thelycum shrimp Litopenaeus (Crustacea: Decapoda: Penaeoidea). Aquaculture 270:436–442

    Google Scholar 

  • Asano A, Nelson JL, Zhang S, Travis AJ (2010) Characterization of the proteomes associating with three distinct membrane raft sub-types in murine sperm. Proteomics 10:3494–3505

    CAS  PubMed  PubMed Central  Google Scholar 

  • Aungsuchawan S, Browdy CL, Withyachumnarnkul B (2011) Sperm capacitation of the shrimp Litopenaeus vannamei. Aquac Res 42:188–195

    Google Scholar 

  • Bassols J, Bonet S, Belghazi M, Dacheux F, Dacheux JL (2007) Proteomic study of the establishment of boar epididymal cell cultures. Theriogenology 68:76–86

    CAS  PubMed  Google Scholar 

  • Brown DA, London E (1998) Functions of lipid rafts in biological membranes. Annu Rev Cell Dev Biol 14:111–136

    CAS  PubMed  Google Scholar 

  • Chotwiwatthanakun C, Sangatit J, Santimanawong W, Surinlert P, Prommoon J, Weerachatyanukul W, Vanichviriyakit R (2016) Expression of Penaeus monodon ortholog of Niemann–Pick type C-2 in the spermatic tract, and its role in sperm cholesterol removal. Mol Reprod Dev 15:213–227

    Google Scholar 

  • Cornwall GA (2009) New insights into epididymal biology and function. Hum Reprod 15:213–227

    CAS  Google Scholar 

  • Cross NL (1998) Role of cholesterol in sperm capacitation. Biol Reprod 59:7–11

    CAS  PubMed  Google Scholar 

  • Cross NL (2004) Reorganization of lipid rafts during capacitation of human sperm. Biol Reprod 71:1367–1373

    CAS  PubMed  Google Scholar 

  • Flesch FM, Brouwers JF, Nievelstein PF, Verkleij AJ, van Golde LM, Colenbrander B, Gadella BM (2001) Bicarbonate stimulated phospholipid scrambling induces cholesterol redistribution and enables cholesterol depletion in the sperm plasma membrane. J Cell Sci 114:3543–3555

    CAS  PubMed  Google Scholar 

  • Frenette G, Sullivan R (2001) Prostasome & hyphen; like particles are involved in the transfer of P25b from the bovine epididymal fluid to the sperm surface. Mol Reprod Dev 59:115–121

    CAS  PubMed  Google Scholar 

  • Frenette G, Girouard J, Sullivan R (2006) Comparison between epididymosomes collected in the intraluminal compartment of the bovine caput and cauda epididymis. Biol Reprod 75:885–890

    CAS  PubMed  Google Scholar 

  • Friedland N, Liou HL, Lobel P, Stock AM (2003) Structure of a cholesterol-binding protein deficient in Niemann–Pick type C2 disease. Proc Natl Acad Sci U S A 100:2512–2517

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fröhlich O, Young LG (1996) Molecular cloning and characterization of EPI-1, the major protein in chimpanzee (Pan troglodytes) cauda epididymal fluid. Biol Reprod 54:857–864

    PubMed  Google Scholar 

  • Girouard J, Frenette G, Sullivan R (2008) Seminal plasma proteins regulate the association of lipids and proteins within detergent-resistant membrane domains of bovine spermatozoa. Biol Reprod 78:921–931

    CAS  PubMed  Google Scholar 

  • Girouard J, Frenette G, Sullivan R (2011) Comparative proteome and lipid profiles of bovine epididymosomes collected in the intraluminal compartment of the caput and cauda epididymidis. Int J Androl 34:475–486

    Google Scholar 

  • Ishida Y, Tsuchiya W, Fujii T, Fujimoto Z, Miyazawa M, Ishibashi J, Matsuyama S, Ishikawa Y, Yamazaki T (2014) Niemann-Pick type C2 protein mediating chemical communication in the worker ant. PNAS 111:3847–3852

    CAS  PubMed  Google Scholar 

  • Ko DC, Binkley J, Sidow A, Scott MP (2003) The integrity of a cholesterol-binding pocket in Niemann–Pick C2 protein is necessary to control lysosome cholesterol levels. Proc Natl Acad Sci U S A 100:2518–2525

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kruevaisayawan H, Vanichviriyakit R, Weerachatyanukul W, Iamsaard S, Withyachumnarnkul B, Basak A, Tanphaichitr N, Sobhon P (2008) Induction of the acrosome reaction in black tiger shrimp (Penaeus monodon) requires sperm trypsin-like enzyme activity. Biol Reprod 79:134–141

    CAS  PubMed  Google Scholar 

  • Larsen LB, Ravn P, Boisen A, Berglund L, Petersen TE (1997) Primary structure of EPV20, a secretory glycoprotein containing a previously uncharacterized type of domain. Eur J Biochem 243:437–441

    CAS  PubMed  Google Scholar 

  • Légaré C, Verville N, Sullivan R (2004) Vasectomy influences expression of HE1 but not HE2 and HE5 genes in human epididymis. J Adrol 25:30–43

    Google Scholar 

  • Légaré C, Thabet M, Gatti JL, Sullivan R (2006) HE1/NPC2 status in human reproductive tract and ejaculated spermatozoa: consequence of vasectomy. Mol Hum Reprod 12:461–468

    PubMed  Google Scholar 

  • Nakamura Y, Takayama N, Minamitani T, Ikuta T, Ariga H, Mastumoto K (2000) Primary structure, genomic organization and expression of secretary protein of murine epididymis, ME1. Gene 251:55–62

    CAS  PubMed  Google Scholar 

  • Naureckiene S, Sleat DE, Lackland H, Fensom A, Vanier MT, Wattiaux R, Jadot M, Lobel P (2000) Identification of HE1 as the second gene of Niemann-Pick C disease. Science 290:2298–2301

    CAS  PubMed  Google Scholar 

  • Okamura N, Kiuchi S, Tamba M, Kashima T, Hiramoto S, Baba T, Dacheux F, Dacheux JL, Sugita Y, Jin YZ (1999) A porcine homolog of the major secretory protein of human epididymis, HE1, specifically binds cholesterol. BBA-Mol Cell Biol L 1438:377–387

    CAS  Google Scholar 

  • Shadan S, James PS, Howes EA, Jones R (2004) Cholesterol efflux alters lipid raft stability and distribution during capacitation of boar spermatozoa. Biol Reprod 71:253–265

    CAS  PubMed  Google Scholar 

  • Simons K, Toomre D (2000) Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 1:31–39

    CAS  PubMed  Google Scholar 

  • Storch J, Xu Z (2009) Niemann–Pick C2 (NPC2) and intracellular cholesterol trafficking. BBA-Mol Cell BiolL 1791:671–678

    CAS  Google Scholar 

  • Suphamungmee W, Weerachatyanukul W, Poomtong T, Hanna P, Sobhon P (2008) Morphological and biochemical alterations of abalone testicular germ cells and spawned sperm and their fertilizing ability. Mar Biotechnol 10:593–601

    CAS  Google Scholar 

  • Surinlert P, Asuvapongpatana S, Srakaew N, Daungchinda D, Setou M, Weerachatyanukul W (2016) Changes of fatty acids in phosphatidylcholine on sperm membrane during Macrobrachium rosenbergii sperm transit through spermatic duct and lipid analysis in spermatic vesicles. Aquaculture 456:62–69

    CAS  Google Scholar 

  • Tanphaichitr N, Tayabali A, Gradil A, Juneja S, Leveille M, Lingwood CA (1992) Role of a germ cell-specific sulfolipid-immobilizing protein (SLP1) in mouse in vivo fertilization. Mol Reprod Dev 32:17–22

    CAS  PubMed  Google Scholar 

  • Thimon V, Frenette G, Saez F, Thabet M, Sullivan R (2008) Protein composition of human epididymosomes collected during surgical vasectomy reversal: a proteomic and genomic approach. Hum Reprod 23:1698–1707

    CAS  PubMed  Google Scholar 

  • Tulsiani DRP, Zeng HT, Abou-Haila A (2007) Biology of sperm capacitation: evidence for multiple signaling pathways. Soc Reprod Fertil Suppl 63:257–272

    CAS  PubMed  Google Scholar 

  • Vacquier VD (1998) Evolution of gamete recognition proteins. Science 281:1995–1998

    CAS  PubMed  Google Scholar 

  • Vanichviriyakit R, Kruevaisayawan H, Weerachatyanukul W, Tawipreeda P, Withyachumnarnkul B, Pratoomchat B, Chavadej J, Sobhon P (2004) Molecular modification of Penaeus monodon sperm in female thelycum and its consequent responses. Mol Reprod Dev 69:356–363

    CAS  PubMed  Google Scholar 

  • Visconti PE, Ning X, Fornés MW, Alvarez JG, Stein P, Connors SA, Kopf GS (1999) Cholesterol efflux-mediated signal transduction in mammalian sperm: cholesterol release signals an increase in protein tyrosine phosphorylation during mouse sperm capacitation. Dev Biol 214:429–443

    CAS  PubMed  Google Scholar 

  • Weerachatyanukul W, Rattanachaiyanont M, Carmona E, Furimsky A, Mai A, Shoushtarian A, Sirichotiyakul S, Balakier H, Leader A, Tanphaichitr N (2001) Sulfogalactosylglycerolipid is involved in human gamete interaction. Mol Reprod Dev 60:569–578

    CAS  PubMed  Google Scholar 

  • Wheelwright M, Kim EW, Inkeles MS, De Leon A, Pellegrini M, Krutzik SR, Liu PT (2014) All-trans retinoic acid–triggered antimicrobial activity against Mycobacterium tuberculosis is dependent on NPC2. J Immunol 192:2280–2290

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wolfe CA, James PS, Mackie AR, Ladha S, Jones R (1998) Regionalized lipid diffusion in the plasma membrane of mammalian spermatozoa. Biol Reprod 59:1506–1514

    CAS  PubMed  Google Scholar 

  • Wüstner D, Solanko K (2015) How cholesterol interacts with proteins and lipids during its intracellular transport. Biochem Biophys Acta 1848:1908–1926

    PubMed  Google Scholar 

  • Xu S, Benoff B, Liou HL, Lobel P, Stock AM (2007) Structural basis of sterol binding by NPC2, a lysosomal protein deficient in Niemann-Pick type C2 disease. J Biol Chem 282:23525–23531

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yanagimachi R (1994) Fertility of mammalian spermatozoa: its development and relativity. Zygote 2:371–372

    CAS  PubMed  Google Scholar 

  • Zhang H, Jones R, Martin-DeLeon PA (2004) Expression and secretion of rat SPAM1 (2B1 or PH-20) in the epididymis: role of testicular lumicrine factors. Matrix Biol 22:653–661

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We appreciate the help from Dr. Thanapong Kruangkum and Dr. Saowaros Suwansa-ard for their bioinformatics analysis and Prof. David John Ruffolo for manuscript proofreading. We also thank the Center of Nanoimaging (CNI) and the Central Instrument Facility (CIF), Faculty of Science, Mahidol University, for providing instrumental support throughout this work.

Funding

This study was funded by Thammasat University (Grant No. 084/2561) and joint funding between the Thailand Research Fund and Mahidol University (Grant No. RSA5980029).

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Authors and Affiliations

  1. Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand

    Piyaporn Surinlert

  2. Center of Excellence for Shrimp Molecular Biology and Biotechnology, Mahidol University, Bangkok, Thailand

    Piyaporn Surinlert, Charoonroj Chotwiwatthanakun & Rapeepun Vanichviriyakit

  3. Department of Anatomy, Faculty of Science, Mahidol University, Rama 6 Rd., Ratchathewi, Bangkok, 10400, Thailand

    Chompoonut Sukonset, Thitiporn Khongkha, Rapeepun Vanichviriyakit, Wattana Weerachatyanukul & Somluk Asuvapongpatana

  4. Mahidol University, Nakhonsawan Campus, Nakhon Sawan, Thailand

    Charoonroj Chotwiwatthanakun

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  1. Piyaporn Surinlert
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Correspondence to Somluk Asuvapongpatana.

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All animal experiments were conducted in accordance with the guidelines of the Animal Care and Use Committee of Thammasart University (TU-ICUC, protocol no. 016/2561).

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Surinlert, P., Sukonset, C., Khongkha, T. et al. Existence and distribution of Niemann–Pick type 2C (NPC2) in prawn reproductive tract and its putative role as a cholesterol modulator during sperm transit in the vas deferens. Cell Tissue Res 382, 381–390 (2020). https://doi.org/10.1007/s00441-020-03225-6

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