ZHANG Tai-Yuan1, YUE Lin-Xiu1, ZHANG Xue-Lian1, TANG Qi1, LI Xin-Yi1, GUO Zhen-Gang1,2,3,*, PAN Chuan-Ying1,*
1 College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China;; 2 Animal Husbandry and Veterinary Science Institute of Bijie City, Bijie 551700, China; 3 Guizhou Xinwumeng Ecological Animal Husbandry Development Co., Ltd., Hezhang 553200, China
Abstract：Retinoic acid, an active metabolite of vitamin A, is the essential exogenous signal during spermatogenesis. However, the role and regulatory mechanism of retinoic acid signaling in spermatogenesis are not clear. In this review, the generation, transduction, receiving and remove of retinoic acid signal and downstream genes regulated by retinoic acid during spermatogenesis were summarized, which would not only provide some references for the further study of the regulation mechanism of retinoic acid signal in spermatogenesis, but also lay a theoretical foundation for ensuring and improving the fecundity of livestock.
[1] Abdulkareem T A, Al-Haboby A H, Al-Mjamei S M, et al.2005. Sperm abnormalities associated with vitamin A deficiency in rams[J]. Small Ruminant Research, 57(1):67~71. [2] Agrimson K S, Oatley M J, Mitchell D, et al.2017. Retinoic acid deficiency leads to an increase in spermatogonial stem number in the neonatal mouse testis, but excess retinoic acid results in no change[J]. Developmental Biology, 432(2): 229-236. [3] Agrimson K S, Onken J, Mitchell D, et al.2016. Characterizing the spermatogonial response to retinoic acid during the onset of spermatogenesis and following synchronization in the neonatal mouse testis[J], Biology of Reproduction, 95(4):81. [4] Akmal K M, Dufour J M, Kim K H.1997. Retinoic acid receptor alpha gene expression in the rat testis: Potential role during the prophase of meiosis and in the transition from round to elongating spermatids[J]. Biology of Reproduction, 56(2):549-556. [5] Albalat R.2009. The retinoic acid machinery in invertebrates: ancestral elements and vertebrate innovations[J]. Molecular and Cellular Endocrinology, 313(1-2):23-35. [6] Arnold S L, Kent T, Hogarth C A, et al.2015. Importance of ALDH1A enzymes in determining human testicular retinoic acid concentrations[J]. Journal of Lipid Research, 56(2): 342-357. [7] Balmer J E, Blomhoff R.2002. Gene expression regulation by retinoic acid[J]. Journal of Lipid Research, 43(11):1773-1808. [8] Bannister L A, Reinholdt L G, Munroe R J, et al.2004. Positional cloning and characterization of mouse mei8, a disrupted allelle of the meiotic cohesin Rec8[J]. Genesis, 40(3): 184-194. [9] Baroni T, Arato I, Mancuso F, et al.2019. On the origin of testicular germ cell tumors: From gonocytes to testicular cancer[J]. Frontiers in endocrinology, 10: 343. [10] Barua A B, Furr H C.1998. Properties of retinoids. Structure, handling, and preparation[J]. Molecular Biotechnology, 10(2):167-182. [11] Beedle M T, Stevison F, Zhong G, et al.2019. Sources of all-trans retinal oxidation independent of the aldehyde dehydrogenase 1A isozymes exist in the postnatal testis[J]. Biology of Reproduction, 100(2): 547-560. [12] Belyaeva O V, Adams M K, Wu L, et al.2017. The antagonistically bifunctional retinoid oxidoreductase complex is required for maintenance of all-trans-retinoic acid homeostasis[J]. The Journal of Biological Chemistry, 292(14): 5884-5897. [13] Chen Y, Ma L, Hogarth C, et al.2016. Retinoid signaling controls spermatogonial differentiation by regulating expression of replication-dependent core histone genes[J]. Development, 143(9): 1502-1511. [14] Cheng P, Chen H, Liu S R, et al.2013. SNPs in KIT and KITLG genes may be associated with oligospermia in Chinese population[J]. Biomarkers, 18(8): 650-654. [15] Chung S S, Wang X, Roberts S S, et al.2011. Oral administration of a retinoic acid receptor antagonist reversibly inhibits spermatogenesis in mice[J]. Endocrinology, 152(6): 2492-2502. [16] Chung S S, Wang X, Wolgemuth D J.2009. Expression of retinoic acid receptor alpha in the germline is essential for proper cellular association and spermiogenesis during spermatogenesis[J]. Development, 136(12): 2091-2100. [17] Chung S S, Wolgemuth D J.2004. Role of retinoid signaling in the regulation of spermatogenesis[J]. Cytogenetic and Genome Research, 105(2-4):189-202. [18] Comitato R, Esposito T, Cerbo G, et al.2006. Impairment of spermatogenesis and enhancement of testicular germ cell apoptosis induced by exogenous all-trans-retinoic acid in adult lizard Podarcis sicula[J]. Journal of Experimental Zoology. Part A, Comparative Experimental Biology, 305(3): 288-298. [19] Cool J, DeFalco T, Capel B.2012. Testis formation in the fetal mouse: Dynamic and complex de novo tubulogenesis[J]. Wiley Interdisciplinary Reviews. Developmental Biology, 1(6): 847-859. [20] Cunningham T J, Zhao X, Duester G.2011. Uncoupling of retinoic acid signaling from tailbud development before termination of body axis extension[J]. Genesis, 49(10):776-783. [21] Das B C, Thapa P, Karki R, et al.2014. Retinoic acid signaling pathways in development and diseases[J]. Bioorganic & Medicinal Chemistry, 22(2): 673-683. [22] de Rooij D G, Griswold M D.2012. Questions about spermatogonia posed and answered since 2000[J]. Journal of Andrology, 33(6): 1085-1095. [23] de Rooij D G.2001. Proliferation and differentiation of spermatogonial stem cells[J]. Reproduction, 121(3): 347-354. [24] Donovan M, Olofsson B, Gustafson A L, et al.1995. The cellular retinoic acid binding proteins[J]. The Journal of Steroid Biochemistry and Molecular Biology, 53(1-6):459-465. [25] Doyle T J, Braun K W, McLean D J, et al.2007. Potential functions of retinoic acid receptor A in Sertoli cells and germ cells during spermatogenesis[J]. Annals of the New York Academy of Sciences, 1120: 114-130. [26] Du G, Oatley M J, Law N C, et al.2021. Proper timing of a quiescence period in precursor prospermatogonia is required for stem cell pool establishment in the male germline[J]. Development, 148(9): dev194571. [27] Duester G.2008. Retinoic acid synthesis and signaling during early organogenesis[J]. Cell, 134(6): 921-931. [28] Dufour J M, Kim K H.1999. Cellular and subcellular localization of six retinoid receptors in rat testis during postnatal development: identification of potential heterodimeric receptors[J]. Biology of Reproduction, 61(5):1300-1308. [29] Ebata K T, Zhang X, Nagano M C, et al.2005. Expression patterns of cell-surface molecules on male germ line stem cells during postnatal mouse development[J]. Molecular Reproduction and Development, 72(2):171-181. [30] Ehmcke J, Wistuba J, Schlatt S.2006. Spermatogonial stem cells: Questions, models and perspectives[J]. Human Reproduction Update, 12(3): 275-282. [31] Endo T, Freinkman E, de Rooij D G, et al.2017. Periodic production of retinoic acid by meiotic and somatic cells coordinates four transitions in mouse spermatogenesis[J]. Proceedings of the National Academy of Sciences of the USA, 114(47): E10132-E10141. [32] Ferder I C, Fung L, Ohguchi Y, et al.2019. Meiotic gatekeeper STRA8 suppresses autophagy by repressing Nr1d1 expression during spermatogenesis in mice[J]. PLoS Genetics, 15(5): e1008084. [33] Galan J J, De Felici M, Buch B, et al.2006. Association of genetic markers within the KIT and KITLG genes with human male infertility[J]. Human Reproduction (Oxford, England), 21(12): 3185-3192. [34] Gely-Pernot A, Raverdeau M, Célébi C, et al.2012. Spermatogonia differentiation requires retinoic acid receptor γ[J]. Endocrinology, 153(1): 438-449. [35] Gilbert S F.2000. Developmental Biology. 6th edition[M]. Sunderland (MA): Sinauer Associates. Spermatogenesis. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10095/ [36] Goto S, Onishi A, Misaki K, et al.2018. Neural retina-specific Aldh1a1 controls dorsal choroidal vascular development via Sox9 expression in retinal pigment epithelial cells[J]. Elife, 7: e32358. [37] Griswold M D, Hogarth C.2018. Beyond stem cells: Commitment of progenitor cells to meiosis[J]. Stem Cell Research, 27: 169-171. [38] Hamer G, de Rooij D G.2018. Mutations causing specific arrests in the development of mouse primordial germ cells and gonocytes[J]. Biology of Reproduction, 99(1):75-86. [39] Hirota Y, Kurohmaru M, Matsumoto M, et al.1994. Stage-synchronization of the seminiferous tubules after vitamin A replacement in vitamin A deficient golden hamsters[J]. The Journal of Veterinary Medical Science, 56(3):439-442. [40] Hogarth C A, Arnold S, Kent T, et al.2015a. Processive pulses of retinoic acid propel asynchronous and continuous murine sperm production[J]. Biology of Reproduction, 92(2): 37. [41] Hogarth C A, Evans E, Onken J, et al.2015b. CYP26 enzymes are necessary within the postnatal seminiferous epithelium for normal murine spermatogenesis[J]. Biology of Reproduction, 93(1): 19. [42] Hogarth C A, Griswold M D.2010. The key role of vitamin A in spermatogenesis[J]. The Journal of clinical investigation, 120(4): 956-962. [43] Hwang Y S, Suzuki S, Seita Y, et al.2020. Reconstitution of prospermatogonial specification in vitro from human induced pluripotent stem cells[J]. Nature Communications, 11(1): 5656. [44] Ikami K, Tokue M, Sugimoto R, et al.2015. Hierarchical differentiation competence in response to retinoic acid ensures stem cell maintenance during mouse spermatogenesis[J]. Development, 142(9):1582-1592. [45] Imura-Kishi K, Uchida A, Tsunekawa N, et al.2021. Low retinoic acid levels mediate regionalization of the Sertoli valve in the terminal segment of mouse seminiferous tubules[J]. Scientific Reports, 11(1): 1110. [46] Ismail N, Morales C, Clermont Y.1990. Role of spermatogonia in the stage-synchronization of the seminiferous epithelium in vitamin-A-deficient rats[J]. The American Journal of Anatomy, 188(1): 57-63. [47] Isoherranen N, Zhong G.2019. Biochemical and physiological importance of the CYP26 retinoic acid hydroxylases[J]. Pharmacology & Therapeutics, 204: 107400. [48] Kastner P, Mark M, Leid M, et al.1996. Abnormal spermatogenesis in RXR beta mutant mice[J]. Genes & Development, 10(1): 80-92. [49] Kedishvili N Y.2013. Enzymology of retinoic acid biosynthesis and degradation[J]. Journal of Lipid Research, 54:1744-1760. [50] Kelly M, Widjaja-Adhi M A, Palczewski G, et al.2016. Transport of vitamin A across blood-tissue barriers is facilitated by STRA6[J]. FASEB Journal, 30(8): 2985-2995. [51] Koli S, Mukherjee A, Reddy K V R.2017. Retinoic acid triggers c-kit gene expression in spermatogonial stem cells through an enhanceosome constituted between transcription factor binding sites for retinoic acid response element (RARE), spleen focus forming virus proviral integration oncogene (SPFI1) (PU.1) and E26 transformation-specific (ETS)[J]. Reproduction, Fertility, and Development, 29(3): 521-543. [52] Koopman P, Gubbay J, Vivian N, et al.1991. Male development of chromosomally female mice transgenic for Sry[J]. Nature, 351: 117-121. [53] Koubova J, Hu Y C, Bhattacharyya T, et al.2014. Retinoic acid activates two pathways required for meiosis in mice[J]. PLoS Genetics, 10(8): e1004541. [54] Koubova J, Menke D B, Zhou Q, et al.2006. Retinoic acid regulates sex-specific timing of meiotic initiation in mice[J]. Proceedings of the National Academy of Sciences of the USA, 103(8): 2474-2479. [55] Krezel W, Ghyselinck N, Samad T A, et al.1998. Impaired locomotion and dopamine signaling in retinoid receptor mutant mice[J]. Science, 279(5352): 863-867. [56] Larsen R, Proue A, Scott E P, et al.2019. The thalamus regulates retinoic acid signaling and development of parvalbumin interneurons in postnatal mouse prefrontal cortex[J]. eNeuro, 6(1): ENEURO.0018-19.2019. [57] Lee K, Skromne I.2014. Retinoic acid regulates size, pattern and alignment of tissues at the head-trunk transition[J]. Development, 141(22): 4375-4384. [58] Li H, MacLean G, Cameron D, et al.2009. Cyp26b1 expression in murine Sertoli cells is required to maintain male germ cells in an undifferentiated state during embryogenesis[J]. PLoS One, 4(10): e7501. [59] Li X, Sun T, Wang X, et al.2019. Restore natural fertility of Kitw/Kitwv mouse with nonobstructive azoospermia through gene editing on SSCs mediated by CRISPR-Cas9[J]. Stem Cell Research & Therapy, 10(1): 271. [60] Liu R Z, Garcia E, Glubrecht D D, et al.2015. CRABP1 is associated with a poor prognosis in breast cancer: Adding to the complexity of breast cancer cell response to retinoic acid[J]. Molecular Cancer, 14: 129. [61] Lohnes D, Kastner P, Dierich A, et al.1993. Function of retinoic acid receptor gamma in the mouse[J]. Cell, 73(4):643-658. [62] Lord T, Oatley J M.2017. A revised Asingle model to explain stem cell dynamics in the mouse male germline[J]. Reproduction, 154(2): R55-R64. [63] Lord T, Oatley M J, Oatley J M.2018. Testicular architecture is critical for mediation of retinoic acid responsiveness by undifferentiated spermatogonial subtypes in the mouse[J]. Stem Cell Reports, 10(2): 538-552. [64] Lu C, Xu M, Wang Y, Qin Y, et al.2013. Genetic variants in meiotic program initiation pathway genes are associated with spermatogenic impairment in a Han Chinese population[J]. PLoS One, 8(1): e53443. [65] MacLean G, Li H, Metzger D, et al.2007. Apoptotic extinction of germ cells in testes of Cyp26b1 knockout mice[J]. Endocrinology, 148(10): 4560-4567. [66] Mangelsdorf D J, Borgmeyer U, Heyman R A, et al.1992. Characterization of three RXR genes that mediate the action of 9-cis retinoic acid[J]. Genes & Development, 6(3): 329-344. [67] Mark M, Jacobs H, Oulad-Abdelghani M, et al.2008. STRA8-deficient spermatocytes initiate, but fail to complete, meiosis and undergo premature chromosome condensation[J]. Journal of Cell Science, 121(Pt 19):3233-3242. [68] Mascrez B, Ghyselinck N B, Watanabe M, et al.2004. Ligand-dependent contribution of RXRbeta to cholesterol homeostasis in Sertoli cells[J]. EMBO Reports, 5(3):285-290. [69] McLaren A.1998. Gonad development: Assembling the mammalian testis[J]. Current Biology: CB, 8(5): R175-R177. [70] McLean D J, Russell L D, Griswold M D.2002. Biological activity and enrichment of spermatogonial stem cells in vitamin A-deficient and hyperthermia-exposed testes from mice based on colonization following germ cell transplantation[J]. Biology of Reproduction, 66(5): 1374-1379. [71] Morales C, Griswold M D.1987. Retinol-induced stage synchronization in seminiferous tubules of the rat[J]. Endocrinology, 121(1): 432-434. [72] Muciaccia B, Sette C, Paronetto M P, et al.2010. Expression of a truncated form of KIT tyrosine kinase in human spermatozoa correlates with sperm DNA integrity[J]. Human Reproduction (Oxford, England), 25(9):2188-2202. [73] Nicholls P K, Schorle H, Naqvi S, et al.2019. Mammalian germ cells are determined after PGC colonization of the nascent gonad[J]. Proceedings of the National Academy of Sciences of the USA, 116(51): 25677-25687. [74] Nihi F, Gomes M L M, Carvalho F A R, et al.2017. Revisiting the human seminiferous epithelium cycle[J]. Human Reproduction (Oxford, England), 32(6): 1170-1182. [75] Nourashrafeddin S, Hosseini Rashidi B, Plant T M, 2017. Stage-specific expression of CYP26B1 in the adult testis is responsible for pulsatile retinoic acid signaling in spermatogenesis[J]. Reproductive Biology, 1(1): 1-7. [76] Nourashrafeddin S, Hosseini Rashidi B.2018. Gonadotropin regulation of retinoic acid activity in the testis[J]. Acta Medica Iranica, 56(1): 34-42. [77] Orr-Urtreger A, Avivi A, Zimmer Y, et al.1990. Developmental expression of c-kit, a proto-oncogene encoded by the W locus[J]. Development, 109(4): 911-923. [78] Packer A I, Besmer P, Bachvarova R F, et al.1995. Kit ligand mediates survival of type A spermatogonia and dividing spermatocytes in postnatal mouse testes[J]. Molecular Reproduction and Development, 42(3): 303-310. [79] Prabhu SM, Meistrich M L, McLaughlin E A, et al.2006. Expression of c-Kit receptor mRNA and protein in the developing, adult and irradiated rodent testis[J]. Reproduction, 131(3): 489-499. [80] Rajan N, Kidd G L, Talmage D A, et al.1991. Cellular retinoic acid-binding protein messenger RNA: Levels in rat tissues and localization in rat testis[J]. Journal of Lipid Research, 32(7): 1195-1204. [81] Raverdeau M, Gely-Pernot A, Féret B, et al.2012. Retinoic acid induces Sertoli cell paracrine signals for spermatogonia differentiation but cell autonomously drives spermatocyte meiosis[J]. Proceedings of the National Academy of Sciences of the USA, 109(41): 16582-16587. [82] Rhinn M, Dollé P.2012. Retinoic acid signalling during development[J]. Development, 139(5): 843-858. [83] Samarut E, Fraher D, Laudet V, et al.2015. ZebRA: An overview of retinoic acid signaling during zebrafish development[J]. Biochimica et Biophysica Acta, 1849(2):73-83. [84] Schrans-Stassen B H, van de Kant H J, de Rooij D G, et al.1999. Differential expression of c-kit in mouse undifferentiated and differentiating type A spermatogonia[J]. Endocrinology, 140(12): 5894-5900. [85] Snyder E M, Davis J C, Zhou Q, et al.2011. Exposure to retinoic acid in the neonatal but not adult mouse results in synchronous spermatogenesis[J]. Biology of Reproduction, 84(5): 886-893. [86] Snyder E M, Small C, Griswold M D.2010. Retinoic acid availability drives the asynchronous initiation of spermatogonial differentiation in the mouse[J]. Biology of Reproduction, 83(5): 783-790. [87] Stoney P N, Fragoso Y D, Saeed R B, et al.2016. Expression of the retinoic acid catabolic enzyme CYP26B1 in the human brain to maintain signaling homeostasis[J]. Brain Structure & Function, 221(6): 3315-3326. [88] Subash S K, Kumar P G.2021. Spermatogonial stem cells: A story of self-renewal and differentiation[J]. Frontiers in bioscience (Landmark edition), 26: 163-205. [89] Tanaka S S, Nishinakamura R.2014. Regulation of male sex determination: Genital ridge formation and Sry activation in mice[J]. Cellular and Molecular Life Sciences, 71(24): 4781-4802. [90] Teletin M, Vernet N, Yu J, et al.2019. Two functionally redundant sources of retinoic acid secure spermatogonia differentiation in the seminiferous epithelium[J]. Development, 146(1): dev170225. [91] Theodosiou M, Laudet V, Schubert M.2010. From carrot to clinic: an overview of the retinoic acid signaling pathway[J]. Cellular and Molecular Life Sciences, 67(9):1423-1445. [92] Tian H, Billings T, Petkov P M.2021. EWSR1 affects PRDM9-dependent histone 3 methylation and provides a link between recombination hotspots and the chromosome axis protein REC8[J]. Molecular Biology of the Cell, 32(1): 1-14. [93] Tong M H, Yang Q E, Davis J C, et al.2013. Retinol dehydrogenase 10 is indispensible for spermatogenesis in juvenile males[J]. Proceedings of the National Academy of Sciences of the USA, 110(2): 543-548. [94] van Pelt A M, De Rooij D G.1990. Synchronization of the seminiferous epithelium after vitamin A replacement in vitamin A-deficient mice[J]. Biology of Reproduction, 43(3): 363-367. [95] Vermot J, Pourquié O.2005. Retinoic acid coordinates somitogenesis and left-right patterning in vertebrate embryos[J]. Nature, 435(7039): 215-220. [96] Vernet N, Dennefeld C, Guillou F, et al.2006a. Prepubertal testis development relies on retinoic acid but not rexinoid receptors in Sertoli cells[J]. The EMBO Journal, 25(24): 5816-5825. [97] Vernet N, Dennefeld C, Klopfenstein M, et al.2008. Retinoid X receptor beta (RXRB) expression in Sertoli cells controls cholesterol homeostasis and spermiation[J]. Reproduction, 136(5): 619-626. [98] Vernet N, Dennefeld C, Rochette-Egly C, et al.2006b. Retinoic acid metabolism and signaling pathways in the adult and developing mouse testis[J]. Endocrinology, 147(1):96-110. [99] Wang Z, Kim K H.1993. Vitamin A-deficient testis germ cells are arrested at the end of S phase of the cell cycle: A molecular study of the origin of synchronous spermatogenesis in regenerated seminiferous tubules[J]. Biology of Reproduction, 48(5): 1157-1165. [100] Wilson V, Olivera-Martinez I, Storey K G.2009. Stem cells, signals and vertebrate body axis extension[J]. Development, 136(10): 1591-1604. [101] Yang J, Wu C, Stefanescu I, et al.2017. Analysis of retinoic acid-induced neural differentiation of mouse embryonic stem cells in two and three-dimensional embryoid bodies[J]. Journal of Visualized Experiments, (122): 55621. [102] Ye L, Li X, Li L, et al.2017. Insights into the development of the adult leydig cell lineage from stem leydig cells[J]. Frontiers in Physiology, 8: 430. [103] Yokota S, Sekine N, Wakayama T, et al.2021. Impact of chronic vitamin A excess on sperm morphogenesis in mice[J]. Andrology, 9(5): 1579-1592. [104] Yokota S, Shirahata T, Yusa J, et al.2019. Long-term dietary intake of excessive vitamin A impairs spermatogenesis in mice[J]. The Journal of Toxicological Sciences, 44(4): 257-271. [105] Yoon S W, Lee M S, Xaver M, et al.2016. Meiotic prophase roles of Rec8 in crossover recombination and chromosome structure[J]. Nucleic Acids Research, 44(19): 9296-9314. [106] Yoshida S.2016. From cyst to tubule: Innovations in vertebrate spermatogenesis[J]. Wiley Interdisciplinary Reviews. Developmental Biology, 5(1): 119-131. [107] Yoshinaga K, Nishikawa S, Ogawa M, et al.1991. Role of c-kit in mouse spermatogenesis: identification of spermatogonia as a specific site of c-kit expression and function[J]. Development, 113(2): 689-699. [108] Yue F, Cheng Y, Breschi A, et al.2014. Mouse ENCODE Consortium. A comparative encyclopedia of DNA elements in the mouse genome[J]. Nature, 515(7527): 355-364. [109] Zhang M, Zhou H, Zheng C, et al.2014. The roles of testicular c-kit positive cells in de novo morphogenesis of testis[J]. Scientific Reports, 4: 5936. [110] Zheng W L, Bucco R A, Schmitt M C, et al.1996. Localization of cellular retinoic acid-binding protein (CRABP) II and CRABP in developing rat testis[J]. Endocrinology, 137(11): 5028-5035. [111] Zhou Q, Nie R, Li Y, et al.2008. Expression of stimulated by retinoic acid gene 8 (Stra8) in spermatogenic cells induced by retinoic acid: An in vivo study in vitamin A-sufficient postnatal murine testes[J]. Biology of Reproduction, 79(1): 35-42.
