Central Role of 5′-AMP-Activated Protein Kinase in Chicken Sperm Functions1

Nguyen, Thi Mong Diep; Alves, Sabine; Grasseau, Isabelle; Métayer-Coustard, Sonia; Praud, Christophe; Froment, Pascal; Blesbois, Élisabeth

doi:10.1095/biolreprod.114.121855

Cited by 70 publications

(82 citation statements)

References 59 publications

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“…Moreover, metformin was found to enhance the phosphorylation of 5'-AMP activated protein kinase (AMPK), which is a sensor protein of cellular energy status, thus, a strategic enzyme in regulating energy balances (i.e., glucose and lipid metabolism) (Bertoldo et al, 2015;Hardie et al, 2003;Ma et al, 2015;Nguyen et al, 2014Nguyen et al, , 2015. Therefore, metformin may improve sperm function via enhancing the activity of AMPK.…”

Section: Positive Effectsmentioning

confidence: 99%

Section: Positive Effectsmentioning

confidence: 99%

“…Adding metformin at 50 µM to cryopreservation media of mouse semen improved the quality (motility and morphology) of frozen sperm (Bertoldo et al, 2014). A recent study conducted by Nguyen et al (2014) showed that metformin enhances chicken sperm motility and viability, and increases acrosome reaction and lactate production (Nguyen et al, 2014).The clinical study that displays the effect of metformin on sperm parameters was recently conducted by Bosman et al (2014) on hyperinsulinaemic men (Bosman et al, 2014). This group showed that administration of metformin at the therapeutic dose improves sperm morphology (from 3.9% to 5.5%) and enhances chromatin packaging quality by about 8.3% (Bosman et al, 2014).…”

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confidence: 99%

“…Similar findings of enhancing the antioxidant function were observed when using diet-induced obesity rats (i.e., higher superoxide dismutase and glutathione peroxidase, and lower malondialdehyde) (Fang et al, 2012). In fact, metformin was identified as having antioxidant activity against oxidative damage by reactive oxygen species (Cahova et al., 2015;Ouslimani et al, 2005).Moreover, metformin was found to enhance the phosphorylation of 5'-AMP activated protein kinase (AMPK), which is a sensor protein of cellular energy status, thus, a strategic enzyme in regulating energy balances (i.e., glucose and lipid metabolism) (Bertoldo et al, 2015;Hardie et al, 2003;Ma et al, 2015;Nguyen et al, 2014Nguyen et al, , 2015. Therefore, metformin may improve sperm function via enhancing the activity of AMPK.…”

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Effect of metformin on semen quality

Banihani

2016

Braz. J. Pharm. Sci.

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Various studies have linked metformin, a universally antidiabetic drug, with semen quality; however, such a direct link has not been established. This review systematically addresses and summarizes the effect of metformin on semen quality, particularly sperm function. We searched the MEDLINE electronic database for English articles and abstracts containing the key words 'metformin' and 'sperm', and relevant articles were reviewed. In summary, metformin appears to have improved and provided positive impact on sperm quality. This effect may be due to the ability of metformin to reduce oxidative stress and lipid peroxidation, enhance 5'-AMP activated protein kinase activity, and restore the normal levels of pituitary-gonadal hormones. However, further clinical research is still necessary to confirm such effect.Uniterms: Metformin/effects. Metformin/review. Metformin/semen quality. Sperm/study. Testosterone. Oxidative stress. 5'-AMP activated protein kinase. INTRODUCTIONMetformin, a biguanide-derivative antidiabetic drug, is the most widely used oral agent in humans (Brinkmann, Brixius, 2015;Chhetri, Thapa, Van Schepdael, 2014). It is the first-line drug for the treatment of type 2 diabetes, particularly, in overweight and obese patients with normal kidney function (American Diabetes, 2009;George, Joseph, 2014;Hung et al., 2015). In addition, recent research has proposed that metformin alone or in combination with insulin may be safe to treat gestational diabetes and does not increase the risk of metabolic acidosis (Huang, Castelino, Peterson, 2015; Kitwitee et al., 2015). Metformin's mechanism of action involves suppression of hepatic gluconeogenesis (Ferrannini, 2014; Foretz et al., 2010;Todd, Florez, 2014). One concern that has been raised relevant to metformin usage is that the consensus panel of diabetes felt that metformin should be considered for diabetes prevention even in non-diabetic individuals (i.e., pre-diabetic or obese individuals). This concern increases the use of this drug by these groups (American Diabetes, 2009;Hostalek, Gwilt, Hildemann, 2015;Manu et al., 2015;McGavock, Dart, Wicklow, 2015).Over the last decade, various experimental and clinical studies have linked metformin with sperm function, and thus with male factor infertility Ferreira et al., 2015); however, such direct link has not been established. In this review, we provide fresh and comprehensive understanding of the effect of metformin, as a universally used oral agent, on semen quality (i.e., sperm quantity and quality). To do this, we searched the MEDLINE electronic database for English-language articles and abstracts reported using the key words 'metformin' and 'sperm'. The references from selected articles were reviewed and used if relevant. Effect of metformin on sperm parameters Positive effectsTo date, the majority of studies linking metformin to sperm parameters are nonclinical. In his study on streptozotocin-induced diabetic rats, Attia, Helal, Alhaider (2009) made the seminal observation that metformin decreases the diabe...

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Section: Positive Effectsmentioning

confidence: 99%

Section: Positive Effectsmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Effect of metformin on semen quality

Banihani

2016

Braz. J. Pharm. Sci.

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“…However, there is evidence that metformin does not negatively impact the quality of fresh mouse spermatozoa, and its presence in cryopreservation protocols may induce a benefit for the postthaw quality of frozen semen (Bertoldo et al 2014a). A metformin-mediated improvement of sperm motility and viability was obtained after this procedure was applied to chicken spermatozoa (Nguyen et al 2014). The main mechanism of action of metformin is not completely elucidated.…”

Section: Introductionmentioning

confidence: 99%

The insulin sensitiser metformin regulates chicken Sertoli and germ cell populations

Faure¹,

Guibert²,

Alves³

et al. 2016

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Metformin, an insulin sensitiser from the biguanide family of molecules, is used for the treatment of insulin resistance in type 2 diabetes individuals. It increases peripheral glucose uptake and may reduce food intake. Based on the tight link between metabolism and fertility, we investigated the role of metformin on testicular function using in vitro culture of Sertoli cells and seminiferous tubules, complemented by in vivo data obtained following metformin administration to prepubertal chickens. In vitro, metformin treatment reduced Sertoli cell proliferation without inducing apoptosis and morphological changes. The metabolism of Sertoli cells was affected because lactate secretion by Sertoli cells increased approximately twofold and intracellular free ATP was negatively impacted. Two important pathways regulating proliferation and metabolism in Sertoli cells were assayed. Metformin exposure was not associated with an increased phosphorylation of AKT or ERK. There was a 90% reduction in the proportion of proliferating germ cells after a 96-h exposure of seminiferous tubule cultures to metformin. In vivo, 6-week-old chickens treated with metformin for 3 weeks exhibited reduced testicular weight and a 50% decrease in testosterone levels. The expression of a marker of undifferentiated germ cells was unchanged in contrast to the decrease in expression of 'protamine', a marker of differentiated germ cells. In conclusion, these results suggest that metformin affects the testicular energy content and the proliferative ability of Sertoli and germ cells.

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The seminal acrosin‐inhibitor ClTI1/SPINK2 is a fertility‐associated marker in the chicken

Thélie

Réhault-Godbert

Poirier

et al. 2019

Molecular Reproduction Devel

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The seminal plasma is a very complex fluid, which surrounds sperm in semen. It contains numerous proteins including proteases and protease inhibitors that regulate proteolytic processes associated with protein activation and degradation. We previously identified a seminal protein, chicken liver trypsin inhibitor 1 (ClTI‐1) over expressed in semen of roosters with high fertility, suggesting a role in male fertility. In the present study, we showed that ClTI‐1 gene is actually SPINK2. Using normal healthy adult roosters, we showed that SPINK2 amount in seminal plasma was positively correlated with male fertility in chicken lines with highly contrasted genetic backgrounds (broiler and layer lines). Using affinity chromatography combined to mass spectrometry analysis and kinetic assays, we demonstrated for the first time that two chicken acrosin isoforms (acrosin and acrosin‐like proteins) are the physiological serine protease targets of SPINK2 inhibitor. SPINK2 transcript was overexpressed all along the male tract, and the protein was present in the lumen as expected for secreted proteins. Altogether, these data emphasize the role of seminal SPINK2 Kazal‐type inhibitor as an important actor of fertility in birds through its inhibitory action on acrosin isoforms proteins.

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Central Role of 5′-AMP-Activated Protein Kinase in Chicken Sperm Functions1

Cited by 70 publications

References 59 publications

Effect of metformin on semen quality

Effect of metformin on semen quality

The insulin sensitiser metformin regulates chicken Sertoli and germ cell populations

The seminal acrosin‐inhibitor ClTI1/SPINK2 is a fertility‐associated marker in the chicken

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