Occurrence of D-aspartic acid in human seminal plasma and spermatozoa: Possible role in reproduction

D’Aniello, Gemma; Ronsini, Salvatore; Guida, Francesco; Spinelli, Patrizia; D’Aniello, Antimo

doi:10.1016/j.fertnstert.2005.05.019

Cited by 80 publications

(58 citation statements)

References 21 publications

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“…Total RNA was extracted from the cells using the RNeasy Mini Kit (Qiagen, Hilden, Germany), according to the manufacturer's instructions. For first-strand cDNA synthesis, the RNA samples (5 µg) were reverse-transcribed in a 20 µL reaction mixture containing 200 units of SuperScript III Reverse Transcriptase and 0.5 µg of oligo(dT) [12][13][14][15][16][17][18] primer (Invitrogen, Carlsbad, CA, U.S.A.). After incubation at 50°C for 1 h, 1 µL (2 units) of RNaseH (Invitrogen) was added and the mixture was incubated at 37°C for 20 min.…”

Section: Methodsmentioning

confidence: 99%

“…[13][14][15] The amounts of D-Asp in human seminal plasma and spermatozoa are significantly lower in oligoasthenoteratospermic and azoospermic donors than normospermic donors. 16) Furthermore, in female patients undergoing in vitro fertilization, the D-Asp content of pre-ovulatory follicular fluid is lower in older patients than in younger patients; this decrease in D-Asp content appears to reflect a reduction in oocyte quality and fertilization competence. 17) Overall, current evidence suggests that decreases in D-Asp levels may be involved in the pathophysiology of infertility.…”

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confidence: 99%

“…DDO inhibitors may also be lead compounds for the development of new drugs to treat infertility since D-Asp is thought to be involved in the quality control of germ cells. 16,17) Overall, human DDO is an attractive therapeutic target and several compounds that inhibit the activity of mammalian DDO in vitro have been identified to date; however, the inhibitory potency of these compounds is limited. [28][29][30][31][32][33] Preclinical studies using experimental rodents are essential prerequisites for evaluating the in vivo effects of clinically useful enzyme inhibitors.…”

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confidence: 99%

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Characterization of the Enzymatic and Structural Properties of Human D-Aspartate Oxidase and Comparison with Those of the Rat and Mouse Enzymes

Katane

Kawata

Nakayama

et al. 2015

Biological & Pharmaceutical Bulletin

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Human DDO is considered an attractive therapeutic target, and DDO inhibitors may be potential lead compounds for the development of new drugs against the aforementioned diseases. However, human DDO has not been characterized in detail and, although preclinical studies using experimental rodents are prerequisites for evaluating the in vivo effects of potential inhibitors, the existence of species-specific differences in the properties of human and rodent DDOs is still unclear. Here, the enzymatic activity and characteristics of purified recombinant human DDO were analyzed in detail. The kinetic and inhibitor-binding properties of this enzyme were also compared with those of purified recombinant rat and mouse DDOs. In addition, structural models of human, rat, and mouse DDOs were generated and compared. It was found that the differences among these DDO proteins occur in regions that appear involved in migration of the substrate/product in and out of the active site. In summary, detailed characterization of human DDO was performed and provides useful insights into the use of rats and mice as experimental models for evaluating the in vivo effects of DDO inhibitors. Alzheimer's disease, 9,10) and amyotrophic lateral sclerosis. Key words 11,12)Unlike the tissue-specific expression of D-Ser, substantial amounts of free D-Asp are present in a wide variety of mammalian tissues and cells, particularly those of the central nervous, neuroendocrine, and endocrine systems. Several lines of evidence suggest that D-Asp plays an important role in regulating developmental processes, hormone secretion, and steroidogenesis. [13][14][15] The amounts of D-Asp in human seminal plasma and spermatozoa are significantly lower in oligoasthenoteratospermic and azoospermic donors than normospermic donors. 16) Furthermore, in female patients undergoing in vitro fertilization, the D-Asp content of pre-ovulatory follicular fluid is lower in older patients than in younger patients; this decrease in D-Asp content appears to reflect a reduction in oocyte quality and fertilization competence. 17) Overall, current evidence suggests that decreases in D-Asp levels may be involved in the pathophysiology of infertility. Furthermore, D-Asp stimulates the NMDA receptor by acting as an agonist that binds to the L-Glu-binding site of the receptor. 18,19) Recent studies have suggested that, similar to D-Ser, D-Asp acts as a signaling molecule in nervous and neuroendocrine systems, at least in part, by binding to the NMDA receptor, and plays an important role in the regulation of brain functions. 14,15,20) In support of this proposal, it was reported recently that D-Asp levels in the prefrontal cortex and striatum of post-mortem brains of schizophrenic patients are significantly lower than those of non-psychiatrically ill individuals. 21) In mammalian tissues, two types of degradative enzymes that are stereospecific for D-amino acids have been identified, namely, D-amino acid oxidase (DAO, also abbreviated as DAAO; EC 1.4.3.3) and D-Asp oxidase (DDO, also ab...

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Characterization of the Enzymatic and Structural Properties of Human D-Aspartate Oxidase and Comparison with Those of the Rat and Mouse Enzymes

Katane

Kawata

Nakayama

et al. 2015

Biological & Pharmaceutical Bulletin

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“…These observations suggest that D-Asp is an important regulatory molecule of gonads. In addition, it was recently shown that the amount of D-Asp in human seminal plasma and spermatozoa is significantly reduced in oligoasthenoteratospermic and/or azoospermic donors compared with normospermic donors (14). Moreover, in human female patients undergoing in vitro fertilization, the D-Asp content of the preovulatory follicular fluid is lower in older patients than in younger ones (15).…”

mentioning

confidence: 99%

Spatiotemporal Localization of d-Amino Acid Oxidase and d-Aspartate Oxidases during Development in Caenorhabditis elegans

Saitoh

Katane

Kawata

et al. 2012

Molecular and Cellular Biology

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(58,61). Its concentration in the blood of silkworms was reported to increase during particular stages of metamorphosis, although the physiological role of D-Ser in metamorphosis remains unclear (11). It is also present in the mammalian forebrain, where it persists at high concentrations throughout the life of the animal. DSer is now considered a neuromodulator that binds to the glycinebinding site of the N-methyl-D-Asp (NMDA) receptor, a subtype of the L-glutamate (L-Glu) receptor, and potentiates glutamatergic neurotransmission in the central nervous system (51,60,68). In fact, astroglia-derived D-Ser has been shown to regulate NMDA receptor-dependent long-term potentiation and/or long-term depression, which are basic processes of learning and memory, in the hypothalamic and hippocampal excitatory synapses (25,54). In addition, D-Ser is also found in the cerebellum during the early postnatal period, and it was recently reported that D-Ser derived from the Bergmann glia serves as an endogenous ligand for the ␦2 L-Glu receptor to regulate long-term depression at synapses between parallel fibers and Purkinje cells in the immature cerebellum but not the mature one (31). These lines of evidence suggest the physiological significance of D-Ser in the regulation of higher brain functions through the L-Glu receptors, and indeed, perturbation of D-Ser levels in the central nervous system has now been implicated in the pathophysiology of various neuropsychiatric disorders, including schizophrenia (4, 23, 24, 71), Alzheimer's disease (28, 70), and amyotrophic lateral sclerosis (59).Unlike the tissue-specific expression of D-Ser, substantial amounts of free D-Asp are present in a wide variety of tissues and cells in invertebrates and vertebrates, particularly in the central nervous, neuroendocrine, and endocrine systems. D-Asp is proposed to play an important role in regulating developmental processes, hormone secretion, and steroidogenesis (12,26,35). For instance, it has been reported that in male lizards, intraperitoneally administered D-Asp is taken up rapidly by the testis, which induces a significant increase in testosterone levels and a significant decrease in 17␤-estradiol levels in the testis and plasma (57). Interestingly, a reverse relationship is found between males and females; specifically, in female lizards, exogenous D-Asp induces a significant decrease in testosterone levels in the ovary and plasma, while it enhances follicular production of 17␤-estradiol by upregulating the local aromatase activity (2). Similar findings have also been reported in studies of the green frog (16, 56). These observations suggest that D-Asp is an important regulatory molecule of gonads. In addition, it was recently shown that the amount of D-Asp in human seminal plasma and spermatozoa is significantly reduced in oligoasthenoteratospermic and/or azoospermic donors compared with normospermic donors (14). Moreover, in human female patients undergoing in vitro fertilization, the D-Asp content of the preovulatory follicular fluid ...

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“…For instance, it is involved in cerebral hormone secretion in the mammalian brain. 2) In the genital tract, it is probably related to fertilization processes, 3) and is involved in the acceleration of testosterone synthesis in the testis. 4) A variety of foods have been reported to contain significant amounts of D-amino acids.…”

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confidence: 99%

Enzymatic Assay forD-Aspartic Acid UsingD-Aspartate Oxidase and Oxaloacetate Decarboxylase

Kato

Ikuta

Hemmi

et al. 2012

Bioscience, Biotechnology, and Biochemistry

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Occurrence of D-aspartic acid in human seminal plasma and spermatozoa: Possible role in reproduction

Cited by 80 publications

References 21 publications

Characterization of the Enzymatic and Structural Properties of Human D-Aspartate Oxidase and Comparison with Those of the Rat and Mouse Enzymes

Characterization of the Enzymatic and Structural Properties of Human D-Aspartate Oxidase and Comparison with Those of the Rat and Mouse Enzymes

Spatiotemporal Localization of d-Amino Acid Oxidase and d-Aspartate Oxidases during Development in Caenorhabditis elegans

Enzymatic Assay forD-Aspartic Acid UsingD-Aspartate Oxidase and Oxaloacetate Decarboxylase

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