Pathogenesis and mitigation of the deleterious effects of heat stress on bull reproduction / Patogênese e mitigação dos efeitos deletérios do estresse térmico na reprodução de touros

Bull testes must be 2 to 6 0C below body temperature for morphologically normal, motile and fertile sperm. Scrotal/testicular thermoregulation is complex, including a coiled testicular artery, surrounded by the venous pampiniform plexus comprising the testicular vascular cone, a counter-current heat exchanger. In addition, heat radiation from the scrotum, sweating, complementary arterial blood supplies, and temperature gradients in the scrotum and testes all contribute to testicular cooling. Despite a long-standing paradigm that mammalian testes are close to hypoxia and blood flow does not increase in response to testicular heating, in recent studies in mice, rams and bulls, warming the testes stimulated increased blood flow, with no indications of testicular hypoxia. Furthermore, hypoxia did not replicate the changes and hyperoxia did not provide protection. Therefore, we concluded that testicular hyperthermia and not secondary hypoxia affects spermatogenesis and sperm quality. Increasing testicular temperature causes many cellular and subcellular changes. As testicular temperature increases, the proportion of defective sperm increases; recovery is dependent upon the nature and duration of the thermal insult. Environmental control of temperature (shade, sprinklers, air conditioning) and some chemical approaches (e.g., melatonin and L-arginine) have promise in reducing the effects of heat stress on bull reproduction.

Os testículos dos bovinos devem permanecer 2 a 6 ºC abaixo da temperatura corporal para produzirem espermatozoides morfologicamente normais, móveis e férteis. A termorregulação escrotal/testicular é complexa e envolve a enovelada artéria testicular circundada pelo plexo venoso pampiniforme, que constituem o cone vascular, um sistema contracorrente de troca de calor. Adicionalmente, a perda de calor por radiação pelo escroto, sudorese, suprimento sanguíneo arterial complementar, e os gradientes de temperatura no escroto e testículos contribuem para o resfriamento testicular. A despeito do duradouro paradigma de que os testículos estão em uma situação de quase hipóxia e que o fluxo sanguíneo não aumenta em resposta ao aquecimento testicular, em recentes estudos em camundongos, carneiros e touros, o aquecimento testicular estimulou o fluxo sanguíneo sem serem observados sinais de hipóxia. Além disso, a hipóxia não afetou os testículos e a hiperóxia não conferiu proteção. Portanto, concluímos que é a hipertermia testicular, e não a hipóxia secundária, que afeta a espermatogênese e a qualidade seminal. O aumento da temperatura testicular causa muitas mudanças celulares e subcelulares. À medida que a temperatura aumenta, a proporção de espermatozoides defeituosos aumenta. A recuperação depende da natureza e duração do insulto térmico. O controle ambiental (sombra, aspersores de água e ar condicionado) e algumas abordagens químicas (ex., melatonina e L-arginina) são medidas promissoras de redução dos efeitos do estresse térmico na reprodução de touros

Na/K-ATPase and Regulation of Sperm Function

A standard bull breeding soundness evaluation (BBSE) identifies bulls with semen that is grossly abnormal. Nonetheless, semen samples classified as satisfactory based on these traditional approaches differ in fertility; perhaps there are submicroscopic differences in sperm characteristics affecting fertility. Therefore, a better understanding of molecular regulation of sperm function could promote development of novel, evidence-based approaches to predict male fertility. Recently the α4 isoform of Na/K-ATPase (ATP1A4) has received considerable attention, due to its testisspecific expression in post-meiotic germ cells and mature sperm, in addition to its regulation of sperm motility and capacitation. Using fresh bull sperm, we determined that ATP1A4 resided in specialized microdomains (raft and non-raft) of the sperm plasma membrane and activated specific signaling (caveolin-1, EGFR, Src, ERK1/2) molecules during sperm capacitation. Furthermore, ATP1A4 was the predominant isoform responsible for total Na/K-ATPase activity in capacitated sperm. Despite the widely accepted dogma of transcriptional/translational quiescence, bovine sperm translated ATP1A4 mRNA on mitochondrial or mitochondrial-type ribosomes, increasing their content and activity during capacitation. Proteomic analysis of raft and non-raft fractions revealed a significant interaction between ATP1A4 and plakoglobin, a member of the β-catenin family of proteins involved in cell adhesion, in the equatorial segment of capacitated sperm, suggesting a potential role in sperm-oolemma fusion. In frozen-thawed sperm, ATP1A4 content and activity was greater in high- versus low-fertility bulls. Additionally, ATP1A4-induced increases in ROS, calcium, actin polymerization and tyrosine phosphorylation were also involved in regulating post-thaw sperm function in these bulls. Overall, results demonstrated that ATP1A4 had unique roles in controlling several aspects of sperm physiology, acting through well-established enzyme activity and signaling functions. Consequently, isoforms of Na/K-ATPase are potential biomarkers for male fertility.

Na/K-ATPase and Regulation of Sperm Function

A standard bull breeding soundness evaluation (BBSE) identifies bulls with semen that is grossly abnormal. Nonetheless, semen samples classified as satisfactory based on these traditional approaches differ in fertility; perhaps there are submicroscopic differences in sperm characteristics affecting fertility. Therefore, a better understanding of molecular regulation of sperm function could promote development of novel, evidence-based approaches to predict male fertility. Recently the α4 isoform of Na/K-ATPase (ATP1A4) has received considerable attention, due to its testisspecific expression in post-meiotic germ cells and mature sperm, in addition to its regulation of sperm motility and capacitation. Using fresh bull sperm, we determined that ATP1A4 resided in specialized microdomains (raft and non-raft) of the sperm plasma membrane and activated specific signaling (caveolin-1, EGFR, Src, ERK1/2) molecules during sperm capacitation. Furthermore, ATP1A4 was the predominant isoform responsible for total Na/K-ATPase activity in capacitated sperm. Despite the widely accepted dogma of transcriptional/translational quiescence, bovine sperm translated ATP1A4 mRNA on mitochondrial or mitochondrial-type ribosomes, increasing their content and activity during capacitation. Proteomic analysis of raft and non-raft fractions revealed a significant interaction between ATP1A4 and plakoglobin, a member of the β-catenin family of proteins involved in cell adhesion, in the equatorial segment of capacitated sperm, suggesting a potential role in sperm-oolemma fusion. In frozen-thawed sperm, ATP1A4 content and activity was greater in high- versus low-fertility bulls. Additionally, ATP1A4-induced increases in ROS, calcium, actin polymerization and tyrosine phosphorylation were also involved in regulating post-thaw sperm function in these bulls. Overall, results demonstrated that ATP1A4 had unique roles in controlling several aspects of sperm physiology, acting through well-established enzyme activity and signaling functions. Consequently, isoforms of Na/K-ATPase are potential biomarkers for male fertility.(AU)