Origin and Role of Testicular Macrophages in Testis Development, Steroidogenesis, and Spermatogenesis.
Gonad
Macrophage
Spermatogenesis
Steroidogenesis
Testis
Journal
Results and problems in cell differentiation
ISSN: 0080-1844
Titre abrégé: Results Probl Cell Differ
Pays: Germany
ID NLM: 0173555
Informations de publication
Date de publication:
2024
2024
Historique:
medline:
16
10
2024
pubmed:
16
10
2024
entrez:
15
10
2024
Statut:
ppublish
Résumé
Testicular macrophages are the principal immune cells in the testis. In addition to their classical immune roles, they regulate male hormone synthesis by Leydig cells, regeneration of Leydig cells, spermatogonia proliferation and differentiation, maintenance of testis-specific environment for sperm formation, and testis development. The juvenile and adult testes contain two distinct macrophage populations with unique tissue localization, genetic markers, morphology, and function. The interstitial macrophages are physically and functionally connected to Leydig cells, while the peritubular macrophages localize around the seminiferous tubules and are crucial for spermatogonia differentiation. Macrophages in the fetal testes regulate testis vasculature formation and clearance of mislocated cells. The origin of testicular macrophages is unclear. Some studies suggest their origin from the yolk sac and others from the bone marrow-derived monocytes. We discuss this issue at the end of this review article.
Identifiants
pubmed: 39406904
doi: 10.1007/978-3-031-65944-7_5
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
137-157Informations de copyright
© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.
Références
Aziz A, Soucie E, Sarrazin S, Sieweke MH (2009) MafB/c-Maf deficiency enables self-renewal of differentiated functional macrophages. Science 326(5954):867–871
doi: 10.1126/science.1176056
Bain CC, Bravo-Blas A, Scott CL, Perdiguero EG, Geissmann F, Henri S, Malissen B, Osborne LC, Artis D, Mowat AM (2014) Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. Nat Immunol 15(10):929–937
doi: 10.1038/ni.2967
Bergh A (1985) Effect of cryptorchidism on the morphology of testicular macrophages: evidence for a Leydig cell-macrophage interaction in the rat testis. Int J Androl 8(1):86–96
doi: 10.1111/j.1365-2605.1985.tb00821.x
Bergh A, Damber JE, Widmark A (1988) Hormonal control of testicular blood flow, microcirculation and vascular permeability. In: Cooke BA, Sharpe RM (eds) The molecular and cellular endocrinology of the testis, Serono Symposia Publication, vol 50. Raven Press, New York, pp 123–134
Bergh A, Damber JE, van Rooijen N (1993) Liposome-mediated macrophage depletion: an experimental approach to study the role of testicular macrophages in the rat. J Endocrinol 136(3):407–413
doi: 10.1677/joe.0.1360407
Bhushan S, Tchatalbachev S, Lu Y, Fröhlich S, Fijak M, Vijayan V, Chakraborty T, Meinhardt A (2015) Differential activation of inflammatory pathways in testicular macrophages provides a rationale for their subdued inflammatory capacity. J Immunol 194(11):5455–64. https://doi.org/10.4049/jimmunol.1401132
Bhushan S, Theas MS, Guazzone VA, Jacobo P, Wang M, Fijak M, Meinhardt A, Lustig L (2020) Immune cell subtypes and their function in the testis. Front Immunol 11:583304
doi: 10.3389/fimmu.2020.583304
Christensen AK, Gillman SW (1969) The correlation of fine structure and function in steroid-secreting cells, with emphasis on those of the gonads. In: McKerns KW (ed) The gonads. Appleton Century-Crofts, New York, pp 415–488
Cohen PE, Chisholm O, Arceci RJ, Stanley ER, Pollard JW (1996) Absence of colony-stimulating factor-1 in osteopetrotic (csfmop/csfmop) mice results in male fertility defects. Biol Reprod 55(2):310–317
doi: 10.1095/biolreprod55.2.310
Coveney D, Cool J, Oliver T, Capel B (2008) Four-dimensional analysis of vascularization during primary development of an organ, the gonad. Proc Natl Acad Sci USA 105(20):7212–7217
doi: 10.1073/pnas.0707674105
De Felici M, Klinger FG, Campolo F, Balistreri CR, Barchi M, Dolci S (2021) To be or not to be a germ cell: the extragonadal germ cell tumor paradigm. Int J Mol Sci 22(11):5982
doi: 10.3390/ijms22115982
DeFalco T, Bhattacharya I, Williams AV, Sams DM, Capel B (2014) Yolk-sac-derived macrophages regulate fetal testis vascularization and morphogenesis. Proc Natl Acad Sci USA 111(23):E2384–E2393
doi: 10.1073/pnas.1400057111
DeFalco T, Potter SJ, Williams AV, Waller B, Kan MJ, Capel B (2015) Macrophages contribute to the spermatogonial niche in the adult testis. Cell Rep 12(7):1107–1119
doi: 10.1016/j.celrep.2015.07.015
Fijak M, Meinhardt A (2006) The testis in immune privilege. Immunol Rev 213:66–81
doi: 10.1111/j.1600-065X.2006.00438.x
Frungieri MB, Calandra RS, Lustig L, Meineke V, Köhn FM, Vogt HJ, Mayerhofer A (2002) Number, distribution pattern, and identification of macrophages in the testes of infertile men. Fertil Steril 78(2):298–306
doi: 10.1016/S0015-0282(02)03206-5
Garcia-Alonso L, Lorenzi V, Mazzeo CI, Alves-Lopes JP, Roberts K, Sancho-Serra C, Engelbert J, Marečková M, Gruhn WH, Botting RA, Li T, Crespo B, van Dongen S, Kiselev VY, Prigmore E, Herbert M, Moffett A, Chédotal A, Bayraktar OA, Surani A, Haniffa M, Vento-Tormo R (2022) Single-cell roadmap of human gonadal development. Nature 607(7919):540–547
doi: 10.1038/s41586-022-04918-4
Gaytan F, Bellido C, Aguilar E, van Rooijen N (1994a) Requirement for testicular macrophages in Leydig cells proliferation and differentiation during prepubertal development in rats. J Reprod Fertil 102:393–399
doi: 10.1530/jrf.0.1020393
Gaytan F, Bellido C, Morales C, Reymundo C, Aguilar E, van Rooijen N (1994b) Selective depletion of testicular macrophages and prevention of Leydig cell repopulation after treatment with ethylene dimethane sulfonate in rats. J Reprod Fertil 101(1):175–182
doi: 10.1530/jrf.0.1010175
Gaytan F, Bellido C, Morales C, Reymundo C, Aguilar E, Van Rooijen N (1994c) Effects of macrophage depletion at different times after treatment with ethylene dimethane sulfonate (EDS) on the regeneration of Leydig cells in the adult rat. J Androl 15(6):558–564
Gaytan F, Bellido C, Aguilar E, van Rooijen N (1995a) Pituitary-testicular axis in rats lacking testicular macrophages. Eur J Endocrinol 132:218–222
doi: 10.1530/eje.0.1320218
Gaytan F, Bellido C, Morales C, Reymundo C, Aguilar E, van Rooijen N (1995b) Response to Leydig cell apoptosis in the absence of testicular macrophages. J Reprod Immunol 29(1):81–94
doi: 10.1016/0165-0378(95)00934-D
Gewiss RL, Schleif MC, Griswold MD (2021) The role of retinoic acid in the commitment to meiosis. Asian J Androl 23(6):549–554
doi: 10.4103/aja202156
Ginhoux F, Guilliams M (2016) Tissue-resident macrophage ontogeny and homeostasis. Immunity 44(3):439–449
doi: 10.1016/j.immuni.2016.02.024
Griswold MD, Bishop PD, Kim KH, Ping R, Siiteri JE, Morales C (1989) Function of vitamin A in normal and synchronized seminiferous tubules. Ann N Y Acad Sci 564:154–172
doi: 10.1111/j.1749-6632.1989.tb25895.x
Gu X, Heinrich A, Li SY, DeFalco T (2023) Testicular macrophages are recruited during a narrow fetal time window and promote organ-specific developmental functions. Nat Commun 14(1):1439
doi: 10.1038/s41467-023-37199-0
Hales DB (1992) Interleukin-l inhibits Leydig cell steroidogenesis primarily by decreasing 17alpha-hydroxylase/C17-20 lyase cytochrome P450 expression. Endocrinology 131:2165–2172
doi: 10.1210/endo.131.5.1425417
Hales DB (1996) Leydig cell-macrophage interactions: an overview. In: Payne AH, Hardy MP, Russell LD (eds) The Leydig cell. Cache River Press, Vienna, pp 451–466
Hales DB (2002) Testicular macrophage modulation of Leydig cell steroidogenesis. J Reprod Immunol 57(1-2):3–18
doi: 10.1016/S0165-0378(02)00020-7
Hedger MP, Qin JX, Robertson DM, de Kretser DM (1990) Intragonadal regulation of immune system functions. Reprod Fertil Dev 2:263–280
doi: 10.1071/RD9900263
Heidt T, Courties G, Dutta P, Sager HB, Sebas M, Iwamoto Y, Sun Y, Da Silva N, Panizzi P, van der Laan AM, Swirski FK, Weissleder R, Nahrendorf M (2014) Differential contribution of monocytes to heart macrophages in steady-state and after myocardial infarction. Circ Res 115(2):284–295
doi: 10.1161/CIRCRESAHA.115.303567
Hume DA, Halpin D, Charlton H, Gordon S (1984) The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80: macrophages of endocrine organs. Proc Natl Acad Sci USA 81(13):4174–4177
doi: 10.1073/pnas.81.13.4174
Hutson JC (1990) Changes in the concentration and size of testicular macrophages during development. Biol Reprod 43:885–890
doi: 10.1095/biolreprod43.5.885
Hutson JC (1993) Secretion of tumor necrosis factor alpha by testicular macrophages. J Reprod Immunol 23:63–72
doi: 10.1016/0165-0378(93)90027-F
Hutson JC (1994) Testicular macrophages. Int Rev Cytol 149:99–143
doi: 10.1016/S0074-7696(08)62087-2
Hutson JC (2006) Physiologic interactions between macrophages and Leydig cells. Exp Biol Med (Maywood) 231:1–7
doi: 10.1177/153537020623100101
Kern S, Maddocks S (1995) Indomethacin blocks the immunosuppressive activity of rat testicular macrophages cultured in vitro. J Reprod Immunol 28(3):189–201
doi: 10.1016/0165-0378(95)91391-Q
Kern S, Robertson SA, Mau VJ, Maddocks S (1995) Cytokine secretion by macrophages in the rat testis. Biol Reprod 53:1407–1416
doi: 10.1095/biolreprod53.6.1407
Kokkinaki M, Lee TL, He Z, Jiang J, Golestaneh N, Hofmann MC, Chan WY, Dym M (2009) The molecular signature of spermatogonial stem cells in the 6-day-old mouse testis. Biol Reprod 80:707–717
doi: 10.1095/biolreprod.108.073809
Larina IV, Shen W, Kelly OG, Hadjantonakis AK, Baron MH, Dickinson ME (2009) A membrane associated mCherry fluorescent reporter line for studying vascular remodeling and cardiac function during murine embryonic development. Anat Rec (Hoboken) 292(3):333–341
doi: 10.1002/ar.20821
Livera G, Delbes G, Pairault C, Rouiller-Fabre V, Habert R (2006) Organotypic culture, a powerful model for studying rat and mouse fetal testis development. Cell Tissue Res 324(3):507–521
doi: 10.1007/s00441-006-0167-7
Lokka E, Lintukorpi L, Cisneros-Montalvo S, Mäkelä JA, Tyystjärvi S, Ojasalo V, Gerke H, Toppari J, Rantakari P, Salmi M (2020) Generation, localization and functions of macrophages during the development of testis. Nat Commun 11(1):4375
doi: 10.1038/s41467-020-18206-0
Maddocks S, Setchell BP (1990) Recent evidence for immune privilege in the testis. J Reprod Immunol 18:9–18
doi: 10.1016/0165-0378(90)90021-W
Miller SC, Bowman BM, Rowland HG (1983) Structure, cytochemistry, endocytic activity and immunoglobulin(Fc) receptors of rat testicular interstitial-tissue macrophages. Am J Anat 168:1–13
doi: 10.1002/aja.1001680102
Mossadegh-Keller N, Sieweke MH (2018) Testicular macrophages: guardians of fertility. Cell Immunol 330:120–125
doi: 10.1016/j.cellimm.2018.03.009
Mossadegh-Keller N, Gentek R, Gimenez G, Bigot S, Mailfert S, Sieweke MH (2017) Developmental origin and maintenance of distinct testicular macrophage populations. J Exp Med 214(10):2829–2841
doi: 10.1084/jem.20170829
Naito M, Hirotaka N, Kawano S, Umezu H, Zhu H, Moriyama H, Yamomoto T, Takatsuka H, Takei Y (1996) Liposome-encapsulated dichloro-methylene diphosphonate induces macrophage apoptosis in vivo and in vitro. J Leukoc Biol 60:337–344
doi: 10.1002/jlb.60.3.337
Nes WD, Lukyanenko YO, Jia ZH, Quideau S, Howald WN, Pratum TK, West RR, Hutson JC (2000) Identification of the lipophilic factor produced by macrophages that stimulates steroidogenesis. Endocrinology 141(3):953–958
doi: 10.1210/endo.141.3.7350
Niemi M, Sharpe RM, Brown WR (1986) Macrophages in the interstitial tissue of the rat testis. Cell Tissue Res 243:337–344
doi: 10.1007/BF00251049
Oatley JM, Oatley MJ, Avarbock MR, Tobias JW, Brinster RL (2009) Colony stimulating factor 1 is an extrinsic stimulator of mouse spermatogonial stem cell self-renewal. Development 136(7):1191–1199
doi: 10.1242/dev.032243
Perdiguero EG, Geissmann F (2016) The development and maintenance of resident macrophages. Nat Immunol 17(1):2–8
doi: 10.1038/ni.3341
Pöllänen P, Niemi M (1987) Immunohistochemical identification of macrophages, lymphoid cells and HLA antigens in the human testis. Int J Androl 10(1):37–42
doi: 10.1111/j.1365-2605.1987.tb00163.x
Pöllänen P, von Euler M, Söder O (1990) Testicular immunoregulatory factors. J Reprod Immunol 18:51–76
doi: 10.1016/0165-0378(90)90024-Z
Pollard JW, Dominguez MG, Mocci S, Cohen PE, Stanley ER (1997) Effect of the colony-stimulating factor-1 null mutation, osteopetrotic (csfm(op)), on the distribution of macrophages in the male mouse reproductive tract. Biol Reprod 56(5):1290–1300
doi: 10.1095/biolreprod56.5.1290
Ponte R, Dupuy FP, Brimo F, Mehraj V, Brassard P, Belanger M, Yurchenko E, Jenabian MA, Bernard NF, Routy JP, ORCHID Study Group (2018) Characterization of myeloid cell populations in human testes collected after sex reassignment surgery. J Reprod Immunol 125:16–24
doi: 10.1016/j.jri.2017.10.043
Sauter KA, Pridans C, Sehgal A, Tsai YT, Bradford BM, Raza S, Moffat L, Gow DJ, Beard PM, Mabbott NA, Smith LB, Hume DA (2014) Pleiotropic effects of extended blockade of CSF1R signaling in adult mice. J Leukoc Biol 96(2):265–274
doi: 10.1189/jlb.2A0114-006R
Schlatt S, de Kretser DM, Hedger MP (1999) Mitosis of resident macrophages in the adult rat testis. J Reprod Fertil 116:223–228
doi: 10.1530/jrf.0.1160223
Setchell BP, Uksila J, Maddocks S, Pöllänen P (1990) Testis physiology relevant to immunoregulation. J Reprod Immunol 18:19–32
doi: 10.1016/0165-0378(90)90022-X
Sieweke MH, Allen JE (2013) Beyond stem cells: self-renewal of differentiated macrophages. Science 342(6161):1242974
doi: 10.1126/science.1242974
Stefater JA 3rd, Ren S, Lang RA, Duffield JS (2011) Metchnikoff’s policemen: macrophages in development, homeostasis and regeneration. Trends Mol Med 17:743–752
doi: 10.1016/j.molmed.2011.07.009
van Rooijen N, Sanders A (1994) Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. J Immunol Methods 174:83–93
doi: 10.1016/0022-1759(94)90012-4
Wang J, Wreford NGM, Lan HY, Atkins R, Hedger MP (1994) Leukocyte populations of the adult rat testis following removal of the Leydig cells by treatment with ethane dimethane sulfonate and subcutaneous testosterone implants. Biol Reprod 51:551–561
doi: 10.1095/biolreprod51.3.551
Wang M, Fijak M, Hossain H, Markmann M, Nüsing RM, Lochnit G, Hartmann MF, Wudy SA, Zhang L, Gu H, Konrad L, Chakraborty T, Meinhardt A, Bhushan S (2017) Characterization of the micro-environment of the testis that shapes the phenotype and function of testicular macrophages. J Immunol 198(11):4327–4340
doi: 10.4049/jimmunol.1700162
Wang M, Yang Y, Cansever D, Wang Y, Kantores C, Messiaen S, Moison D, Livera G, Chakarov S, Weinberger T, Stremmel C, Fijak M, Klein B, Pleuger C, Lian Z, Ma W, Liu Q, Klee K, Händler K, Ulas T, Schlitzer A, Schultze JL, Becher B, Greter M, Liu Z, Ginhoux F, Epelman S, Schulz C, Meinhardt A, Bhushan S (2021) Two populations of self-maintaining monocyte-independent macrophages exist in adult epididymis and testis. Proc Natl Acad Sci USA 118(1):e2013686117
doi: 10.1073/pnas.2013686117
Wilson L (1954) Sperm agglutinins in human semen and blood. Proc Soc Exp Biol Med 85(4):652–655
doi: 10.3181/00379727-85-20982
Winnall WR, Muir JA, Hedger MP (2011) Rat resident testicular macrophages have an alternatively activated phenotype and constitutively produce interleukin-10 in vitro. J Leukoc Biol 90:133–143
doi: 10.1189/jlb.1010557
Wynn TA, Chawla A, Pollard JW (2013) Macrophage biology in development, homeostasis and disease. Nature 496:445–455
doi: 10.1038/nature12034
Xiong Y, Hales DB (1993) The role of tumor necrosis factor-alpha in the regulation of mouse Leydig cell steroidogenesis. Endocrinology 132:2438–2444
doi: 10.1210/endo.132.6.8504748
Xiong Y, Hales DB (1994) Immune-endocrine interactions in the mouse testis: cytokine-mediated inhibition of Leydig cell steroidogenesis. Endocr J 9:1277–1283
Yee JB, Hutson JC (1983) Testicular macrophages: isolation, characterization and hormonal responsiveness. Biol Reprod 29:1319–1326
doi: 10.1095/biolreprod29.5.1319
Yee JB, Hutson JC (1985a) Effects of testicular macrophage-conditioned medium on Leydig cells in culture. Endocrinology 116(6):2682–2684
doi: 10.1210/endo-116-6-2682
Yee JB, Hutson JC (1985b) In vivo effects of FSH on testicular macrophages. Biol Reprod 32:880–883
doi: 10.1095/biolreprod32.4.880
Yee JB, Hutson JC (1985c) Biochemical consequences of FSH binding to testicular macrophages in culture. Biol Reprod 32:872–879
doi: 10.1095/biolreprod32.4.872