D-Aspartic Acid in Vertebrate Reproduction: Animal Models and Experimental Designs ‡
Abstract
:1. Introduction
2. Wild Animals
2.1. In Vivo Experiments
2.2. In Vitro Experiments
3. Laboratory Animals
3.1. In Vivo Experiments
3.2. In Vitro Experiments
4. Livestock Animals
4.1. In Vivo Experiments
4.2. In Vitro Experiments
5. Primates
6. Humans
7. Conclusions and Future Perspectives
Author Contributions
Funding
Conflicts of Interest
References
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BREEDING SEASON | OUT-OF-BREEDING SEASON | ||||||||
---|---|---|---|---|---|---|---|---|---|
a) Long-term experiments | |||||||||
Injections of 2 µmol/g b.w./d D-Asp for 10–15 days | D-Asp uptake | Increase/Decrease | D-Asp uptake | Increase/Decrease | References | ||||
P. esculentus ♂ | |||||||||
Testis | +96% | >1000% E2 +19% StAR mRNA +80% P450 aro mRNA | +100% | +67% T −90% E2 +500% [D-AspO] +43% StAR mRNA +54% 5α-Red2 mRNA | Burrone et al. [33] | ||||
Brain | +450% | −60% T +100% E2 +43% P-CREB +40% P450 aro mRNA +175% P450 aro protein −25 % AR mRNA +25% ERα mRNA | +400% | +140% D-AspO activity +120% caspase 3 | Burrone et al. [36] Burrone et al. [33] Santillo et al. [35] | ||||
b) Short-term experiments | |||||||||
One Injection of 2 µmol/g b.w./ D-Asp | D-Asp uptake | Increase/Decrease | D-Asp uptake | Increase/Decrease | References | ||||
3 h | 6 h | 3 h | 6 h | 3 h | 6 h | 3 h | 6 h | ||
P. esculentus ♂ | |||||||||
Testis | +500% | +800% | +475% T | +25% T | Raucci et al. [40] | ||||
Serum | +255% T | +33% T | Raucci and Di Fiore [29] | ||||||
♀ | |||||||||
Ovary | +900% | +775% | −52% T | −21% T | Di Fiore et al. [31] | ||||
Serum | −82% T | −47% T | −50% T | −83% T | Raucci and Di Fiore [29] | ||||
P. s. sicula ♂ | |||||||||
Testis | +140% | +100% | +32% T −50% E2 | +20% T −37% E2 | +800% | +500% | +96% T −71% E2 +23% c-Kit −50% PK | +78% T −42% E2 +130% PTK +29% PCNA | Raucci et al. [27] Raucci and Di Fiore [28] |
Serum | +5% T −25% E2 | +23% T −75% E2 | +450% T −61% E2 | +1150% T −84% E2 | |||||
♀ | |||||||||
Ovary | >1000% | >1000% | −37% T +200% E2 | −12% T +80% E2 | Assisi et al. [30] | ||||
Serum | −42% T +300% E2 | −28% T +100% E2 | Raucci and Di Fiore [32] |
Incubation | Increase/Decrease | References | |
---|---|---|---|
P. esculentus (breeding season) | |||
Ovarian follicles | +2 μmol/mL D-Asp (3 h) | −62%T | Di Fiore et al. [31] |
Ovarian follicles + pituitary | +2 μmol/mL D-Asp (3 h) | −56%T | |
P. s. sicula (out-of-breeding season) | |||
Ovarian tissue | +2 μmol/mL D-Asp (3 h) | +700% Aromatase activity | Assisi et al. [30] |
Acetonic powder of ovarian follicles | +2 μmol/mL D-Asp (3 h) | +566% Aromatase activity | |
A. platyrhyncos (out-of-breeding season) | |||
Testis slices | +1–2 mM D-Asp (3 h) | +33–150% T | Di Fiore et al. [25] |
D-Asp Uptake | Increase/Decrease | References | |
---|---|---|---|
Sexually immature B6N Mice | +14–20% IVF | Raspa et al. [48] | |
20 mM D-Asp drinking solution for 1–6 weeks | |||
♂ | |||
Testis | +71% T +300–360% Epitestosterone +170% LH | ||
Serum | +25–46% T +36–81% Epitestosterone +36–46% LH | ||
Wistar Rats Prepubertal Injections of 100–500 mg/kg b.w./d D-Asp for 7 days | |||
♂ | |||
Testis | + 75% mitochondrial ROS +30% cytosol ROS +20–50% MDA, hydroperoxide levels, LPO, GSH, catalase activity, GPX, GST, LDH, 3β-HSD, NO, D-AspO −15% MDH | Chandrashakar and Muralidhara [49] | |
Sexually mature 20 mM D-Asp drinking solution | |||
♂ | |||
Testis (treatment for 12–15 days) | +460–720% | +70% T +80% Androstenedione +100–120% P-ERK1/2 +37% StAR (mRNA-protein) +33% P450scc mRNA +38% 3β-HSD mRNA −25% P450 aro protein +55% AR protein −47% ERα protein +130% NR1-NR2A mRNAs | Topo et al. [50] Raucci et al. [40] Santillo et al. [13] |
Pituitary (treatment for 12 days) | +580% | Topo et al. [50] | |
Serum (treatment for 12–15 days) | +100% | +100–120% T +51–128% LH +40% Androstenedione | Topo et al. [50] Raucci et al. [40] |
Brain (treatment for 30 days) | +100% | +40% P +110% T +35% E2 | Di Fiore et al. [51] |
D-Asp Uptake | Increase/Decrease | References | |||||
---|---|---|---|---|---|---|---|
30 min | 1–2 h | 5–8 h | 30 min | 1–2 h | 5–8 h | ||
Wistar Rats One injection of 2 µmol/g b.w. D-Asp | |||||||
♂ | |||||||
Testis | +133% | +311% | +150% NMDA | D’Aniello et al. [41,42] | |||
Adenohypophysis | >1000% | >1000% | +125–166% NMDA | ||||
Hypothalamus | +152% | +267% | +200–860% NMDA | ||||
Epididymis | +500% | +110% | +70% | + 900% T +62% DHT +100% E2 +111 % AR mRNA +233% P450 aro mRNA +166% ERα mRNA | +600% T +62% DHT +80% E2 +200 % 5αRed1 mRNA +150% P450 aro mRNA +366% ERα mRNA | + 450% T +112% DHT +74% E2 +466 % 5αRed1 mRNA +78% % 5αRed2 mRNA +100% P450 aro mRNA +166% ERα | Falvo et al. [52] |
Serum | >1000% | >1000% | +145% PRL | +36% T +34% P +110% LH +200% PRL +97% GH | +236% T +172% P +145% LH +161% GH | D’Aniello et al. [41,42] | |
Brain | +288% | +288% | +211% | +26% T +28% E2 | +80% P +66% T +42% E2 | +90% P +93% T +85% E2 | Di Fiore et al. [51] |
Incubation | Increase/Decrease | References | |
---|---|---|---|
Mouse | |||
Cultured ICR testis tissue | +1–10 mM D-Asp (4 wks) | −21–71% Acr-GFP | Tomita et al [56] |
GC-1 spermatogonia | +200 µM D-Asp (0.5-2 h) | +60–100% GluA1 +157% GluA2/3 +83% P-ERK1/2 +183% P-Akt +29% PCNA +84% AuroraB +266% P450 aro mRNA +62% P450 aro protein +112% ERβ | Santillo et al. [14,57] |
+50 µM NMDA (0.5–4 h) | +66–116% GluA1 +63–75% GluA2/3 +66–133% P-ERK1/2 +33–133% P-ERK2 +40–50% PCNA +40% AuroraB | Santillo et al. [14] | |
Leydig cells | +0.1 nM D-Asp+10 ng/mL hCG (48 h) | +25% T + 83% StAR protein | Di Nisio et al. [58] |
Wistar Rat | |||
Prepubertal testis | +0–1 mM D-Asp (2 h) | +50–280% MDA (cytosol) +83–183% MDA (mitochondria) +143% ROS +332% LPO +82% HP | Chandrashakar and Muralidhara [49,59] |
Immature Leydig cells | +0.2 mM D-Asp (2–24 h) | +112% StAR mRNA +14% P450scc mRNA +33% 3β-HSD mRNA +36% StAR protein +100% Androstenedione release +185% T release | Raucci et al. [40] |
Mature Leydig cells | +200 µM D-Asp (16 h) +200 µM D-Asp (16 h)+ 5 mIU hCG/ml (2 h) | +50% T +250% StAR mRNA +90% StAR protein | Nagata et al. [60,61] |
+0.1 or 1.0 mM D-Asp (1h) | +142–200% T +200–325% cAMP | Topo et al. [50] | |
Hypothalamus | +1 mM D-Asp (0.5 h) | +105% oxytocin | Pampillo et al. [62] |
Adenohypophysis | +0.1–1 mM D-Asp (1 h) | +150–300% PRL +16% LH +166% GH + 150–200% cGMP | D’Aniello et al. [41,42] Topo et al. [50] |
+0.1 mM NMDA (1 h) | +185% GH +83% LH | ||
+0.1–1 mM D-Asp (4 h) (anterior and posterior hypophysis cell coltures) | +11–13% PRL | Pampillo et al. [63] | |
+0.1–1 mM D-Asp (4 h) (anterior hypophysis cell coltures) | +15–25 % PRL | ||
+ 0.01–0.1 mM NMDA (4 h) (anterior hypophysis cell coltures) | +71–110 % PRL | ||
Neurohypophysis | +0.1 mM D-Asp (0.5 h) +0.1 mM NMDA (0.5 h) | −35% oxytocin −45% oxytocin | Pampillo et al. [62] |
Adenohypophysis+ hypothalamus | +1 mM D-Asp (0.5–4 h) | +450% PRL +72% LH +33% GH | D’Aniello et al. [41,42] |
+0.1 mM NMDA (1 h) | +202% LH +87% GH |
a) Long-term experiments | D-Asp uptake | Increase/Decrease | References |
G. g. domesticus | |||
Oral administration of 100–200 mg D-Asp/kg for 12 wks | |||
Testis | +120–680% StAR mRNA +100–1000% P450scc mRNA +100–337% 3β-HSD mRNA +100–766% AR mRNA +120% LHR mRNA +100% Grin1 mRNA +300–1150% Grin2b mRNA +250–1800% PCNA mRNA | Ansari et al. [76] | |
Serum | +10–24% T | ||
Sperm | +sperm motility +Fertility +Hatchability +Plasma membrane integrity +Mitochondrial activity | Ansari et al. [77] | |
O. aries | |||
S.C. administration of 22.2 mg D-Asp/kg b.w. every 3 or 6 days for 1 month | |||
Serum | +40% LH | Boni et al. [67] | |
b) Short-term experiments | D-Asp uptake | Increase/Decrease | References |
O. aries | |||
S.C. injection of 44.4 mg D-Asp/kg b.w. | |||
Ovary | +650% (24 h) | Boni et al. [67] | |
Pituitary | >1000% (12–24 h) | +200% NMDA (12 h) | |
Brain | +125% (12–24 h) | +250% NMDA (12 h) | |
Serum | >1000% (3 h) | >1000% NMDA (5–12 h) +40% LH (2 h) |
Increase/Decrease | References | |
---|---|---|
Oral administration of: | ||
DADAVit® for 12 days | +33% LH +42% T | Topo et al. [50] |
6 g D-Asp for 14 days | −15% T in resistance trained men | Melville et al. [94] |
6 g D-Asp for 3 months | −95% E2 in resistance trained men No positively affecting training outcomes | Melville et al. [95] |
DADAVit® or GENADIS® for 3 months | +sperm concentration and motility in asthenozoospermic and oligoasthenozoospermic men +pregnancy rate | D’Aniello et al. [96] |
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Di Fiore, M.M.; Boni, R.; Santillo, A.; Falvo, S.; Gallo, A.; Esposito, S.; Chieffi Baccari, G. D-Aspartic Acid in Vertebrate Reproduction: Animal Models and Experimental Designs ‡. Biomolecules 2019, 9, 445. https://doi.org/10.3390/biom9090445
Di Fiore MM, Boni R, Santillo A, Falvo S, Gallo A, Esposito S, Chieffi Baccari G. D-Aspartic Acid in Vertebrate Reproduction: Animal Models and Experimental Designs ‡. Biomolecules. 2019; 9(9):445. https://doi.org/10.3390/biom9090445
Chicago/Turabian StyleDi Fiore, Maria Maddalena, Raffaele Boni, Alessandra Santillo, Sara Falvo, Alessandra Gallo, Sabrina Esposito, and Gabriella Chieffi Baccari. 2019. "D-Aspartic Acid in Vertebrate Reproduction: Animal Models and Experimental Designs ‡" Biomolecules 9, no. 9: 445. https://doi.org/10.3390/biom9090445
APA StyleDi Fiore, M. M., Boni, R., Santillo, A., Falvo, S., Gallo, A., Esposito, S., & Chieffi Baccari, G. (2019). D-Aspartic Acid in Vertebrate Reproduction: Animal Models and Experimental Designs ‡. Biomolecules, 9(9), 445. https://doi.org/10.3390/biom9090445