Mitochondrial uncoupling proteins regulate the metabolic function of human Sertoli cells.

In brief: Mitochondrial uncoupling proteins (UCPs) regulate mitochondrial activity and reactive oxygen species production through the transport of protons and metabolites. This study identified the expression of UCPs in human Sertoli cells, which proved to be modulators of their mitochondrial activity. Abstract: Mitochondrial uncoupling proteins (UCPs) are mitochondrial channels responsible for the transport of protons and small molecular substrates across the inner mitochondrial membrane. Altered UCP expression or function is commonly associated with mitochondrial dysfunction and increased oxidative stress, which are both known causes of male infertility. However, UCP expression and function in the human testis remain to be characterized. This study aimed to assess the UCP homologs (UCP1-6) expression and function in primary cultures of human Sertoli cells (hSCs). We identified the mRNA expression of all UCP homologs (UCP1-6) and protein expression of UCP1, UCP2, and UCP3 in hSCs. UCP inhibition by genipin for 24 h decreased hSCs proliferation without causing cytotoxicity (n = 6). Surprisingly, the prolonged UCP inhibition for 24 h decreased mitochondrial membrane potential, oxygen consumption rate (OCR), and endogenous reactive oxygen species (ROS) production. The metabolism of hSCs was also affected as UCP inhibition shifted their metabolism toward an increased pyruvate consumption. Taken together, these findings demonstrate that UCPs play a role as regulators of the mitochondrial function in hSCs, emphasizing their potential as targets in the study of male (in)fertility.

Inhibition of Mitochondrial Uncoupling Proteins Arrests Human Spermatozoa Motility without Compromising Viability.

Mitochondrial uncoupling proteins (UCPs) are central in the regulation of mitochondrial activity and reactive oxygen species (ROS) production. High oxidative stress is a major cause of male infertility; however, UCPs expression and function in human spermatozoa are still unknown. Herein, we aimed to assess the expression and function of the different homologs (UCP1-6) in human spermatozoa. For this purpose, we screened for the mRNA expression of all UCP homologs. Protein expression and immunolocalization of UCP1, UCP2, and UCP3 were also assessed. Highly motile spermatozoa were isolated from human normozoospermic seminal samples (n = 16) and incubated with genipin, an inhibitor of UCPs (0, 0.5, 5, and 50 µM) for 3 h at 37 °C. Viability and total motility were assessed. Mitochondrial membrane potential and ROS production were evaluated. Media were collected and the metabolic profile and antioxidant potential were analyzed by 1H-NMR and FRAP, respectively. The expression of all UCP homologs (UCP1-6) mRNA by human spermatozoa is herein reported for the first time. UCP1-3 are predominant at the head equatorial segment, whereas UCP1 and UCP2 are also expressed at the spermatozoa midpiece, where mitochondria are located. The inhibition of UCPs by 50 µM genipin, resulting in the UCP3 inhibition, did not compromise sperm cell viability but resulted in irreversible total motility loss that persisted despite washing or incubation with theophylline, a cAMP activator. These effects were associated with decreased mitochondrial membrane potential and lactate production. No differences concerning UCP3 expression, however, were observed in spermatozoa from normozoospermic versus asthenozoospermic men (n = 6). The inhibition of UCPs did not increase ROS production, possibly due to the decreased mitochondrial activity and genipin antioxidant properties. In sum, UCPs are major regulators of human spermatozoa motility and metabolism. The discovery and characterization of UCPs' role in human spermatozoa can shed new light on spermatozoa ROS-related pathways and bioenergetics physiology.

Mitochondrial Uncoupling Proteins (UCPs) as Key Modulators of ROS Homeostasis: A Crosstalk between Diabesity and Male Infertility?

Uncoupling proteins (UCPs) are transmembrane proteins members of the mitochondrial anion transporter family present in the mitochondrial inner membrane. Currently, six homologs have been identified (UCP1-6) in mammals, with ubiquitous tissue distribution and multiple physiological functions. UCPs are regulators of key events for cellular bioenergetic metabolism, such as membrane potential, metabolic efficiency, and energy dissipation also functioning as pivotal modulators of ROS production and general cellular redox state. UCPs can act as proton channels, leading to proton re-entry the mitochondrial matrix from the intermembrane space and thus collapsing the proton gradient and decreasing the membrane potential. Each homolog exhibits its specific functions, from thermogenesis to regulation of ROS production. The expression and function of UCPs are intimately linked to diabesity, with their dysregulation/dysfunction not only associated to diabesity onset, but also by exacerbating oxidative stress-related damage. Male infertility is one of the most overlooked diabesity-related comorbidities, where high oxidative stress takes a major role. In this review, we discuss in detail the expression and function of the different UCP homologs. In addition, the role of UCPs as key regulators of ROS production and redox homeostasis, as well as their influence on the pathophysiology of diabesity and potential role on diabesity-induced male infertility is debated.

Azteca barbifex Forel (Hymenoptera: Formicidae): potential pest of citrus crops in eastern Amazon.

Damage caused by the ant Azteca barbifex (Forel) was identified in orange trees (Citrus sinensis), in Capitão Poço County, Guamá microregion, Pará State. The damage caused by the scraping of stems and branches lead to reduction in yield with subsequent death of the plant. These characteristics indicate A. barbifex as a potential pest of citrus crops in the eastern region of Amazon.

Azteca barbifex Forel (Hymenoptera: Formicidae): potential pest of citrus crops in eastern Amazon

Damage caused by the ant Azteca barbifex (Forel) was identified in orange trees (Citrus sinensis), in Capitão Poço County, Guamá microregion, Pará State. The damage caused by the scraping of stems and branches lead to reduction in yield with subsequent death of the plant. These characteristics indicate A. barbifex as a potential pest of citrus crops in the eastern region of Amazon.