In previous research we determined that blocking mAC during
In previous research, we determined that blocking mAC during heparin-induced capacitation result in sperm having a lesser oxygen consumption, suggesting that cAMP produced by this enzyme would be linked to mitochondrial activity and, therefore, with the regulation of sperm metabolism (Fernández and Córdoba, 2014a). The present data suggest that during mAC blocking, heparin-capacitated sperm are characterized by a greater lactate consumption to obtain energy because sperm become less efficient due to a lesser mitochondrial oxidative activity without capacitation. In the presence of heparin and a mAC inhibitor, LDH and CK activities were not modified, so these enzymes could be part of the metabolic pattern of the gamete, not only for energy production but also for maintaining the cellular redox state that preserves sperm viability without allowing capacitation in these conditions.
Recently, capacitation has been divided into fast and slow events (Salicioni et al., 2007). Fast and early events include activation of the vigorous and asymmetric movement of the flagella, while the slow and late events include changes in the pattern of movement for sperm and their acquisition of the ability to carry out the acrosome reaction via stimulation of a physiological agonist and the phosphorylation of tyrosine (Jin and Yang, 2017). Although each of capacitation events has been studied independently, information regarding how they interconnect to regulate sperm motility and to prepare the sperm to undergo the acrosome reaction is still unavailable (Stival et al., 2016). With these advances reported by other authors and adding our results there is evidence that confirm multiple mechanisms of signaling and metabolic pathways that are activated in sperm capacitation. Future researches are required to complete the metabolic map of in vitro sperm capacitation to improve the sonidegib synthesis of reproductive physiology.
Conflict of interest
Acknowledgements The authors would like to thank Centro de Reproducción Bovina SRL for supplying frozen sperm straws, and Astra Laboratories for the supply of ultra-pure water. Research was supported by grants from University of Buenos Aires.
Introduction Migraine and tension-type headache (TTH) are the 2 most common primary headache disorders, affecting >12% and 40% of the population, respectively, and both headache disorders have significant socioeconomic effects , , . Although the pathogenic mechanisms of migraine and TTH are not fully clear, a number of neuropeptides, including calcitonin gene-related peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP) , , play important roles in the pathophysiology of primary headache disorders. Recent studies have indicated the possible involvement of pituitary adenylate cyclase-activating polypeptide (PACAP), another well-characterized neuropeptide, in the pathophysiology of migraine . PACAP belongs to the secretin/glucagon/VIP superfamily, and PACAP and its receptor are widely expressed in nociceptive pathways in the central and peripheral nervous system . Human studies have shown that intravenous PACAP injections can lead to delayed migraine-like attacks migraineurs and are associated with sustained dilatation of extracranial arteries , . Moreover, recent clinical data have indicated that the plasma levels of PACAP increase during migraine attacks, and are reduced in the interictal plasma of migraineurs when compared with that of healthy controls, suggesting an association between plasma PACAP levels and migraine phase . However, the potential use of interictal plasma PACAP levels for distinguishing between migraine and other primary headache disorders has not been investigated. According to the International Classification of Headache Disorders, third edition (ICHD-3 beta) , migraine can be separated into two subtypes based on frequency: episodic migraine (EM) and chronic migraine (CM). Similarly, TTH can be classified as episodic tension-type headache (ETTH) and chronic tension-type headache (CTTH). To date, no studies have examined the interictal plasma PACAP levels in subtypes of migraine and TTH. Therefore, in this study, we aimed to determine interictal plasma PACAP levels in migraineurs (including patients with EM or CM) and patients with TTH (including patients with ETTH and CTTH) compared with matched healthy controls.