Selenium (Se) is an important trace mineral having many essential roles at the cellular and organismal levels in animal and human health. The biological effects of Se are mainly carried out by selenoproteins (encoded by 25 genes in humans and 24 in mice). As an essential component of selenoproteins, Se performs structural and enzymic roles; in the latter context it is well known for its catalytic and antioxidative functions. Studies involving different animal models have added great value to our understanding regarding the potential implications of Se and selenoproteins in mammalian fertility and reproduction.
Selenoprotein Gene * | Symbol [12] | General Description/Function [8][34][35][36][37][38][8,27,43,44,47,56] |
mRNA * | Protein * | Relevance to Male Reproductive Function |
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Glutathione peroxidase 4 | Gpx4 | Detoxification of lipid hydroperoxides, Antioxidant in membranes, functions as structural protein in sperm, also implicated in apoptosis | ++++ | ++++ | Structural protein of sperm midpiece mitochondrial sheath and involved in sperm chromatin condensation [39][75]. Implication in male fertility [27][68]. |
Thioredoxin-glutathione reductase | Txnrd3 (TGR) | Part of the thioredoxin system, Antioxidant function, redox regulation, cell signaling | + | + | Implicated in formation of disulfide bond and sperm maturation process [40][76]. Expressed in post-pubertal testis, particularly abundant in elongated spermatids at the site of mitochondrial sheath formation [39][75]. |
Selenoprotein P | Selenop | Primarily responsible for Se transport and also performs antioxidative role. Considered as a major contributor to plasma Se and a reliable biomarker of Se status. Its deficiency causes infertility characterized by abnormal sperm in mice |
+ | + | Implicated in male fertility [41][42][77,78]. Implicated in transport of Se to spermatogenic cells [30][71]. Essential for sperm development in mice [43][79]. |
Selenoprotein V | Selenov | Largely unidentified, potential role in redox regulation | + | n.d. | Specifically expressed in rodent testes [44][80]. In situ hybridization trials have demonstrated the expression of Selenov mRNA in seminiferous tubules in mouse, however, its precise function in spermatogenesis is largely unexplored [45][44][48,80]. |
Selenoprotein W | Selenow | Antioxidant protection | + | + | n.d. * |
Selenoprotein K | Selenok | Possible antioxidant protection in cardiomyocytes, Endoplasmic reticulum transmembrane protein | ++ | n.d. | n.d. * |
Selenoprotein F | Selenof | Role in cell apoptosis and mediation of chemo-preventive effects of Se | + | n.d. | n.d. * |
Selenoprotein S | Selenos | Cellular redox balance, Possible influence in inflammatory response |
+ | n.d. | n.d. * |
Selenophosphate synthetase 2 | Sephs2 | Required for biosynthesis of selenophosphate, a precursor of selenocysteine, and thus for selenoprotein synthesis | + | n.d. | n.d. |
Model | Treatment | Key Observations Reported | Ref. |
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Sprague-Dawley rats | Se nanoparticles at supranutritional levels (0.2, 0.4, or 0.8 mg Se per kg body weight) | Sperm parameters such as, sperm concentration, motility, and morphological features were all improved at supranutritional levels. However, these parameters were significantly affected when rats were supplemented with higher levels (nonlethal level) of Se nanoparticles i.e., at 2.0, 4.0, or 8.0 mg Se per kg body weight. | [75][110] |
Sprague-Dawley rats | Treated with inorganic Se [0.01(deficient); 0.25 (adequate); 3 (excess); or 5 (excess) mg per kg] for four weeks | The U-shaped response of dietary Se was observed on DNA damage and sperm quality. Se deficiency showed a lower expression of sensitive antioxidant selenoproteins (Gpx1 and Txnrds). However, excessive doses of Se impaired sperm quality and this was linked with reduced mRNA expression of nGpx4. | [76][111] |
Mouse | Se-supplement (inorganic Se (0.3 μg/g Se) or organic Se-enriched probiotics (containing 0.3 μg/g Se) given for 75 days | Organic Se co-supplemented with probiotics significantly improved male fertility in mice. The ameliorated fertility index included the parameters such as, reduced testicular tissue injury, increased levels of serum testosterone, and improved sperm indices in Se-supplemented group. As such, these improved fertility-related parameters were ascribed to be the result of the antioxidant function of Se. | [77][112] |
Mouse | 0.2 ppm sodium selenite; 1.0 ppm sodium selenite |
Mice in both groups showed an increased occurrence of mitochondria- and plasma membrane-related defects, and DNA damage in sperm. However, these damages were more pronounced in mice exposed to Se-deficient feed. | [78][113] |
Mouse | Se-deficient diet (0.02 ppm) Se-sufficient (0.2 ppm); organic Se |
Sperm from Se-deficient mice demonstrated vitiated chromatin condensation, declined in vitro fertilization ability and increased lipid peroxidation (LPO) in both testes and sperm compared to the Se-sufficient mice. | [79][114] |
Mouse | Se-deficient (0.02 ppm) Se-excess (0.2 ppm); yeast-based Se. Mice were fed for 4 months |
Se concentration and GPX activity (in testis) were significantly reduced. The fertility percentage and size of litter were both reduced in Se-deficient group. | [61][96] |
Aged mice | Inorganic Se 0.2 mg/kg body weight | Improved sperm parameters and increased expression of CatSper genes were observed in Se-treated group. | [80][115] |
Rabbit | Treated with Se nanoparticles (400 μg/kg) for 60 days | Improved serum testosterone levels were recorded in Se-treated group compared to the control. Besides, improved ejaculate volume and sperm quality parameters such as, sperm morphology, viability were observed. | [81][116] |
Ram | 0.5 ppm organic Se; 0.2 ppm organic Se | A significantly higher concentration of Se and improved ejaculate and sperm quality were observed in seminal plasma of rams exposed to a feed containing 0.5 ppm organic Se compared to those who received 0.2 ppm organic Se. | [82][117] |
Boar | Organic Se (0.2 mg per kg); Inorganic Se (0.2 mg per kg) |
Ejaculate quality and sperm parameters were significantly improved in boars following dietary supplementation of organic Se (0.2 mg per kg) compared to those treated with sodium selenite at the same dose. | [83][118] |
Aardi buck | Sodium selenite 0.1 mg/kg, Sodium selenite 0.05 mg/kg |
Improved sperm count and motility was observed in both Se-treated groups. However, relatively better outcomes were observed in 0.1 mg/kg group. |
Animal Model and Number | Treatment Regime and Duration | Key Findings | Ref. |
---|---|---|---|
Male CD-1 mice (n = 12 per experimental group) |
Fertilix® (CellOxess, Princeton, NJ, USA) was supplemented for two months. (Se 55 μg, zinc 7.5–11 mg, Full spectrum natural vitamin E 104–290 mg, Lycopene 7.5–15 mg Carnitine blend 200–800 mg Folic acid 400–500 mg Vitamin C 30–90 mg). |
Eight weeks long pretreatment with the antioxidant formulation completely protected oxidative stress-induced DNA damage in Gpx5 KO mice sperm. In mouse models of scrotal heat stress, only 35% (19/54) of female mice became pregnant resulting in 169 fetuses with 18% fetal resorption (30/169). Conversely, in antioxidant pretreated group 74% (42/57) of female mice became pregnant, resulting in 427 fetuses with 9% fetal resorption (38/427). | [91][126] |
Four infertile male dogs with low blood Se levels (86.0–165.0 μg/L) | Organic Se 0.6 mg/kg and vitamin E (5 mg/kg) orally supplemented for 60 days. | Treated dogs showed improved sperm parameters. Increase in blood Se concentration (401 μg/L) was observed at the end of trial. When these dogs were used for matting purpose, bitches successfully conceived and gave birth to 4–6 pups. | [100][136] |
Sixteen healthy normospermic dogs (two patients were excluded after adaptation period) | A supplement comprising of Se 0.27 mg/kg vitamin E 250 mg/kg, vitamin B9 1.5 mg/kg, zinc 180 mg/kg, and n-3 PUFA 0.5%, given for 90 days. | In treated group, sperm quality parameters i.e., total sperm count, concentration, sperm vitality and membrane integrity were significantly improved compared to the control group. | [101][135] |
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Boar | 0.5 ppm organic Se | Following 11 weeks of feeding trail, organic Se supplementation increased glutathione peroxidase 4 (GPX4) activity (raw semen) and number of seminal doses in boars. | [85][120] |
Boar | 0.3 ppm organic Se; 0.3 ppm inorganic Se |
Following 12 weeks of Se supplementation, Se content and GPX activity were increased in semen of boars treated with organic and inorganic Se. Besides, semen quality parameters namely semen concentration and progressive motility of sperm were improved compared to the control group without Se. Improved resistance of liquid stored semen to hypo-osmotic shock and thermal tests, and improved fertility rates were observed in semen of boars treated with Se. All mentioned indices were slightly higher in the organic Se group compared to the inorganic group. | [86][121] |
Buffalo bulls | 10 mg organic Se/animal twice a week; and 10 mg inorganic Se/animal twice a week |
Three months long Se supplementation significantly improved the sperm quality parameters (ejaculate volume, sperm motility, concentration, and morphology) in buffalo bulls. Besides, testosterone concentrations were also increased in Se-treated groups. | [87][122] |
Saanen bucks | Inorganic Se 0.34 mg/kg body weight supplemented at ten-day intervals for three months | Se supplementation improved the testicular biometry and sperm parameters. GPX activity, plasma testosterone and LH levels significantly increased in Se-treated group from days 40 to 80 compared to the control group. These indices reached peak reached peak at day 80 of the trial. | [88][123] |
Bovine bull | In vitro fertilization (IVF) medium supplemented with Se (100 ng/mL) | A significant increase in sperm mitochondrial activity was observed after 1 h of incubation in Se-supplemented IVF medium. Moreover, Se supplementation after 2 h of incubation showed an increase in HOST-positive (hypo-osmotic swelling test) sperm and sperm acrosome integrity. Increased number of sperm bound to zona pellucida (ZP) was observed in Se-treated group compared to the control. | [89][124] |