Rosiglitazone Improves Stallion Sperm Motility, ATP Content, and Mitochondrial Function

Abstract

Media used for equine sperm storage often contain relatively high concentrations of glucose, even though stallion spermatozoa preferentially utilize oxidative phosphorylation (OXPHOS) over glycolysis to generate ATP and support motility. Rosiglitazone is an antidiabetic compound that enhances metabolic flexibility and glucose utilization in various cell types, but its effects on sperm metabolism are unknown. This study investigated the effects of rosiglitazone on stallion sperm function in vitro, along with the possible role of AMP-activated protein kinase (AMPK) in mediating these effects. Spermatozoa were incubated with or without rosiglitazone, GW9662 (an antagonist of peroxisome proliferator-activating receptor-gamma), and compound C (CC; an AMPK inhibitor). Sperm motility, viability, reactive oxygen species production, mitochondrial membrane potential (mMP), ATP content, and glucose uptake capacity were measured. Samples incubated with rosiglitazone displayed significantly higher motility, percentage of cells with normal mMP, ATP content, and glucose uptake capacity, while sperm viability was unaffected. The percentage of spermatozoa positive for mitochondrial ROS was also significantly lower in rosiglitazone-treated samples. AMPK localized to the sperm midpiece, and its phosphorylation, was increased in rosiglitazone-treated spermatozoa. CC decreased sperm AMPK phosphorylation and reduced sperm motility, and successfully inhibited the effects of rosiglitazone. Inclusion of rosiglitazone in a room temperature sperm storage medium maintained sperm motility above 60% for 6 days, attaining significantly higher motility than sperm stored in control media. The ability of rosiglitazone to substantially alleviate the time-dependent deterioration of stallion spermatozoa by diverting metabolism away from OXPHOS and toward glycolysis has novel implications for the long-term, functional preservation of these cells.

5’-AMP-Activated Protein Kinase Regulates Goat Sperm Functions via Energy Metabolism In Vitro

“…AMPK was expressed in the acrosome, midpiece and the entire flagellum of goat sperm, which was in consistence with that in boar [30], human [16,17] and chicken [15] sperm. However, this observation was different to the report by Swegen et al [31] who demonstrated that AMPK was predominantly present in the midpiece and the entire flagellum of stallion sperm. Interestingly, we found that the phospho-Thr172-AMPK was (Fig.…”

“…These observations were different with Hurtado de Llera et al [30], who reported that phospho-Thr172-AMPK was specially present in the most apical region of the acrosome and in the equatorial subsegment of the head, and also in the midpiece of boar sperm after being incubated with TBM or TCM. Moreover, phospho-Thr172-AMPK was present in the principal piece of tail and subequatorial region in the head of stallion sperm [14,31], mainly in the flagellum and acrosome and with a lower intensity in the midpiece of chicken sperm [15]. This contradiction reflects specific localization pattern of phospho-Thr172-AMPK in sperm from different species.…”

UCP2 Mitigates the Loss of Human Spermatozoa Motility by Promoting mROS Elimination

“…Hence, the content of mROS is positively correlated with the levels of ATP and MMP. A positive correlation between mitochondrial energy function and spermatozoa motility has been demonstrated [14,26,35,36]. In these studies, it was found that the levels of MMP and ATP are significantly higher in the NS group than in the AS group, but the mROS levels show a reverse trend, implying that one special mechanism exists in the NS group to either inhibit mROS production or promote mROS elimination.…”

Ortho‐phenylphenol exposure impairs porcine sperm motility through AMPK/AKT signaling pathway

“…It has been reported that ATP production is an essential guarantee for mammalian sperm motility (Tourmente et al ; Swegen et al ). High motility from flagellum movement gives sperm the ability to get through the female reproductive tract to fertilize a mature egg.…”

“…Data were presented as means AE SEM from at least three independent replicates (*P < 0.05; **P < 0.01; ns = no significance). 2015; Swegen et al 2016). High motility from flagellum movement gives sperm the ability to get through the female reproductive tract to fertilize a mature egg.…”