Abstract
d-Aspartate is a natural d-amino acid endogenously present in animal tissues and able to bind to NMDA receptors. The biological actions of d-aspartate have been demonstrated in the central nervous system and in peripheral tissue where the amino acid is under the tight control of two enzymes responsible for its synthesis and degradation, d-aspartate racemase and d-aspartate oxidase, respectively. Furthermore, d-aspartate intervenes on aromatase enzyme functioning.
In the last 20 years, many reports have pointed out this d-amino acid as mediators of critical signals involved together with sex hormones in various aspects of animal and human reproduction. Although mammalian models have been mainly used in the investigation of the role of d-aspartate in reproduction, this amino acid has also been identified in the gonads of nonmammalian animals, in particular in amphibians, reptiles, and birds.
The identification of its occurrence in reproductive cells and organs of vertebrates highlights the key role played by these endogenous compounds along the evolutionary axis. In this review we have summarized the current knowledge of the main actions of d-aspartate on female and male reproductive processes along the evolutionary axis of nonmammalian animals, focusing on the endocrine activity and discussing the interplay between d-aspartate functions and steroid hormones in regulating the reproduction.
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References
Assisi L, Botte V, D’Aniello A, Di Fiore MM (2001) Enhancement of aromatase activity by d-aspartic acid in the ovary of the lizard Podarcis s. sicula. Reproduction 121(5):803–808
Burrone L, Di Giovanni M, Di Fiore MM, Baccari GC, Santillo A (2010) Effects of d-aspartate treatment on d-aspartate oxidase, superoxide dismutase, and caspase 3 activities in frog (Rana esculenta) tissues. Chem Biodivers 7(6):1459–1466
Burrone L, Raucci F, Di Fiore MM (2012a) Steroidogenic gene expression following d-aspartate treatment in frog testis. Gen Comp Endocrinol 175(1):109–117
Burrone L, Santillo A, Pinelli C, Baccari GC, Di Fiore MM (2012b) Induced synthesis of P450 aromatase and 17β-estradiol by d-aspartate in frog brain. J Exp Biol 215(Pt 20):3559–3565
Cangialosi MV, Puccia E, Mazzola A, Mansueto V, Arukwe A (2010) Screening of ovarian steroidogenic pathway in Ciona intestinalis and its modulation after tributyltin exposure. Toxicol Appl Pharmacol 245(1):124–133
D’Aniello A (2007) d-Aspartic acid: an endogenous amino acid with an important neuroendocrine role. Brain Res Rev 53(2):215–234
D’Aniello A, Di Fiore MM, Fisher GH, Milone A, Seleni A, D’Aniello S, Perna AF, Ingrosso D (2000a) Occurrence of d-aspartic acid and N-methyl-d-aspartic acid in rat neuroendocrine tissues and their role in the modulation of luteinizing hormone and growth hormone release. FASEB J 14:699–714
D’Aniello G, Tolino A, D’Aniello A, Errico F, Fisher GH, Di Fiore MM (2000b) The role of d-aspartic acid and N-Methyl-d-Aspartic acid in the regulation of prolactin release. Endocrinology 141:3862–3870
D’Aniello G, Ronsini S, Guida F, Spinelli P, D’Aniello A (2005) Occurrence of d-aspartic acid in human seminal plasma and spermatozoa: possible role in reproduction. Fertil Steril 84(5):1444–1449
D’Aniello G, Grieco N, Di Filippo MA, Cappiello F, Topo E, D’Aniello E, Ronsini S (2007) Reproductive implication of d-aspartic acid in human pre-ovulatory follicular fluid. Hum Reprod 22(12):3178–3183
D’Aniello G, Ronsini S, Notari T, Grieco N, Infante V, D’Angelo N, Mascia F, Di Fiore MM, Fisher G, D’Aniello A (2012) d-Aspartate, a key element for the improvement of sperm quality. Adv Sex Med 2:47–53
D’Aniello A, Di Fiore MM, D’Aniello G, Colin FE, Lewis G, Setchell BP (1998) Secretion of d-aspartic acid by the rat testis and its role in endocrinology of the testis and spermatogenesis. FEBS Lett 436(1):23–27
D’Aniello A, Spinelli P, De Simone A, D’Aniello S, Branno M, Aniello F, Fisher GH, Di Fiore MM, Rastogi RK (2003) Occurrence and neuroendocrine role of d-aspartic acid and N-methyl-d-aspartic acid in Ciona intestinalis. FEBS Lett 552(2–3):193–198
Delrio G, d’Istria M, Milone M, Chieffi G (1971) Identification and biosynthesis of steroid hormones in the gonads of Ciona intestinalis. Experientia 27(11):1348–1350
Di Fiore MM, Perrone L, D’Aniello A (1997) Presence of a human-like thyroid stimulating hormone (TSH) in Ciona intestinalis. Life Sci 61(6):623–629
Di Fiore MM, Assisi L, Botte V, D’Aniello A (1998) d-aspartic acid is implicated in the control of testosterone production by the vertebrate gonad. Studies on the female green frog, Rana esculenta. J Endocrinol 157(2):199–207
Di Fiore MM, Rastogi RK, Ceciliani F, Messi E, Botte V, Botte L, Pinelli C, D’Aniello B, D’Aniello A (2000) Mammalian and chicken I forms of gonadotropin-releasing hormone in the gonads of a protochordate, Ciona intestinalis. Proc Natl Acad Sci U S A 97(5):2343–2348
Di Fiore MM, Lamanna C, Assisi L, Botte V (2008) Opposing effects of d-aspartic acid and nitric oxide on tuning of testosterone production in mallard testis during the reproductive cycle. Reprod Biol Endocrinol 6:28
Di Fiore MM, Santillo A, Chieffi G (2014) Current knowledge of d-aspartate in glandular tissues. Amino Acids 46(8):1805–1818. doi:10.1007/s00726-014-1759-2
Di Giovanni M, Burrone L, Chieffi Baccari G, Topo E, Santillo A (2010) Distribution of free d-aspartic acid and d-aspartate oxidase in frog Rana esculenta tissues. J Exp Zool A Ecol Genet Physiol 313(3):137–143
Falvo S, Di Fiore MM, Burrone L, Baccari GC, Longobardi S, Santillo A (2015) Androgen and oestrogen modulation by d-aspartate in rat epididymis. Reprod Fertil Dev. doi:10.1071/RD15092
Homma H (2007) Biochemistry of d-aspartate in mammalian cells. Amino Acids 32(1):3–11
Huang AS, Beigneux A, Weil ZM, Kim PM, Molliver ME, Blackshaw S, Nelson RJ, Young SG, Snyder SH (2006) d-aspartate regulates melanocortin formation and function: behavioral alterations in d-aspartate oxidase-deficient mice. J Neurosci 26(10):2814–2819
Ishio S, Yamada H, Hayashi M, Yatsushiro S, Noumi T, Yamaguchi A, Moriyama Y (1998) d-aspartate modulates melatonin synthesis in rat pinealocytes. Neurosci Lett 249(2–3):143–146
Lamanna C, Assisi L, Botte V, Di Fiore MM (2006) Endogenous testicular d-aspartic acid regulates gonadal aromatase activity in boar. J Endocrinol Invest 29(2):141–146
Lamanna C, Assisi L, Botte V, Di Fiore MM (2007a) Involvement of D-Asp in P450 aromatase activity and estrogen receptors in boar testis. Amino Acids 32(1):45–51
Lamanna C, Assisi L, Vittoria A, Botte V, Di Fiore MM (2007b) d-Aspartic acid and nitric oxide as regulators of androgen production in boar testis. Theriogenology 67(2):249–254
Ota N, Shi T, Sweedler JV (2012) d-Aspartate acts as a signaling molecule in nervous and neuroendocrine systems. Amino Acids 43(5):1873–1886
Raucci F, Di Fiore MM (2009) The reproductive activity in the testis of Podarcis s. sicula involves d-aspartic acid: a study on c-kit receptor protein, tyrosine kinase activity and PCNA protein during annual sexual cycle. Gen Comp Endocrinol 161(3):373–383
Raucci F, Di Fiore MM (2010) The maturation of oocyte follicular epithelium of Podarcis s. sicula is promoted by d-aspartic acid. J Histochem Cytochem 58(2):157–171
Raucci F, Di Fiore MM (2011) d-Asp: a new player in reproductive endocrinology of the amphibian Rana esculenta. J Chromatogr B Analyt Technol Biomed Life Sci 879(29):3268–3276
Raucci F, Assisi L, D’Aniello S, Spinelli P, Botte V, Di Fiore MM (2004) Testicular endocrine activity is upregulated by d-aspartic acid in the green frog, Rana esculenta. J Endocrinol 182:365–376
Raucci F, D’Aniello S, Di Fiore MM (2005) Endocrine roles of d-Aspartic acid in the testis of lizard Podarcis s. sicula. J Endocrinol 187(3):347–359
Santillo A, Pinelli C, Burrone L, Chieffi Baccari G, Di Fiore MM (2013) d-Aspartic acid implication in the modulation of frog brain sex steroid levels. Gen Comp Endocrinol 181:72–76
Santillo A, Falvo S, Chieffi P, Burrone L, Chieffi Baccari G, Longobardi S, Di Fiore MM (2014) d-aspartate affects NMDA receptor-extracellular signal-regulated kinase pathway and upregulates androgen receptor expression in the rat testis. Theriogenology 81(5):744–751
Santillo A, Falvo S, Chieffi P, Di Fiore MM, Senese R, Chieffi Baccari G (2016) d-Aspartate induces proliferative pathways in spermatogonial GC-1 cells. J Cell Physiol 231(2):490–495
Simpson ER, Mahendroo MS, Means GD, Kilgore MW, Hinshelwood MM, Graham-Lorence S, Amarneh B, Ito Y, Fisher CR, Michael MD et al (1994) Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev 15:342–355
Takigawa Y, Homma H, Lee J-A, Fukushima T, Santa T, Iwatsubo T, Imai K (1998) d-Aspartate uptake into cultured rat pinealocytes and the concomitant effect on l-aspartate levels and melatonin secretion. Biochem Biophys Res Commun 248:641–647
Wang H, Wolosker H, Pevsner J, Snyder SH, Selkoe DJ (2000) Regulation of rat magnocellular neurosecretory system by d-aspartate: evidence for biological role(s) of a naturally occurring free d-amino acid in mammals. J Endocrinol 167(2):247–252
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Di Fiore, M.M., Burrone, L., Santillo, A., Chieffi Baccari, G. (2016). Endocrine Activity of d-Aspartate in Nonmammalian Animals. In: Yoshimura, T., Nishikawa, T., Homma, H. (eds) D-Amino Acids. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56077-7_11
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DOI: https://doi.org/10.1007/978-4-431-56077-7_11
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