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The mu (µ) and delta (δ) opioid receptors modulate boar sperm motility
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0002-0256-1958
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0002-5194-2124
2016 (English)In: Molecular Reproduction and Development, ISSN 1040-452X, E-ISSN 1098-2795, Vol. 83, no 8, 724-734 p.Article in journal (Refereed) Published
Abstract [en]

Endogenous and exogenous opioids modulate reproductive functions in target cells via opioid receptors (µ, δ, and κ). Sperm motility is a metric of gamete functionality, and serves as a suitable parameter for in vitro drug-induced toxicity assays. This study identifies the presence and location of opioid receptors in pig spermatozoa as well as their functional response after in vitro challenge with known agonists (morphine [µ]; [D-Pen 2,5]-enkephanile [δ]; and U 50488 [κ]) and antagonists (naloxone [µ]; naltrindole [δ]; and nor-binaltrorphimine [κ]). Only the µ- and δ-opioid receptors were present in the sperm plasma membrane, overlying the acrosome, neck, and principal piece. Challenge experiments with agonists and antagonists identified both µ- and δ-opioid receptors as regulators of sperm kinematics, wherein µ maintains or increases sperm movement whereas δ decreases sperm motility over time. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
John Wiley & Sons, 2016. Vol. 83, no 8, 724-734 p.
Keyword [en]
opioids, membrane receptors, kinematics, pig
National Category
Developmental Biology
Identifiers
URN: urn:nbn:se:liu:diva-130181DOI: 10.1002/mrd.22675ISI: 000387014800007PubMedID: 27391529OAI: oai:DiVA.org:liu-130181DiVA: diva2:948845
Note

Funding agencies: Swedish Research Council VR, Stockholm [521-2011-6553]; Research Council FORMAS, Sweden [221-2011-512]; Research Council in Southeast Sweden (FORSS), Sweden [378091/31297]

Available from: 2016-07-14 Created: 2016-07-14 Last updated: 2016-12-06Bibliographically approved
In thesis
1. Sperm Membrane Channels, Receptors and Kinematics: Using boar spermatozoa for drug toxicity screening
Open this publication in new window or tab >>Sperm Membrane Channels, Receptors and Kinematics: Using boar spermatozoa for drug toxicity screening
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Internal fertilization usually implies that a spermatozoon, with intact attributes for zygote formation, passes all hurdles during its transport through the female genitalia and reaches the oocyte. During this journey, millions to billions of other spermatozoa perish. Spermatozoa are highly differentiated motile cells without synthetic capabilities. They generate energy via glycolysis and oxidative phosphorylation to sustain motility and to maintain the stability and functionality of their plasma membrane. In vivo, they spend their short lifespan bathing in female genital tract fluids of different origins, or are in vitro exposed to defined media during diverse sperm handling i.e. extension, cryopreservation, in vitro fertilization, etc. Being excitable cells, spermatozoa respond in vivo to various stimuli during pre-fertilization (capacitation, hyperactivation, oocyte location) and fertilization (acrosome reaction, interaction with the oocyte) events, mediated via diverse membrane ion-conducting channels and ligand-gated receptors. The present Thesis has mapped the presence and reactivity (sperm intactness and kinematics) of selected receptors, water and ion channels in ejaculated boar spermatozoa. The final aim was to find a relevant alternative cell type for in vitro bioassays that could ease the early scrutiny of candidate drugs as well as decreasing our needs for experimental animals according to the 3R principles. Spermatozoa are often extended, cooled and thawed to warrant their availability as fertile gametes for breeding or in vitro testing. Such manipulations stress the cells via osmotic variations and hence spermatozoa need to maintain membrane intactness by controlling the exchange of water and the common cryoprotectant glycerol, via aquaporins (AQPs). Both AQPs-7 and -9 were studied for membrane domain changes in cauda- and ejaculated spermatozoa (un-processed, extended, chilled or frozen-thawed). While AQP-9 maintained location through source and handling, thawing of ejaculated spermatozoa clearly relocated the labelling of AQP-7, thus appearing as a relevant marker for non-empirical studies of sperm cryopreservation. Alongside water, spermatozoa interact with calcium (Ca2+) via the main Ca2+ sperm channel CatSper. Increments in intracellular Ca2+ initiate motility hyperactivation and the acrosome reaction. The four subunits of the CatSper channel were present in boar spermatozoa, mediating changes in sperm motility under in vitro capacitation-inducing conditions (increased extracellular Ca2+ availability and bicarbonate) or challenge by the CatSper antagonists mibefradil and NNC 55-0396. Uterine and oviduct fluids are richest in endogenous opioids as β-endorphins during mating and ovulation. Both μ- and δ- opioid receptors were present in boar spermatozoa modulating sperm motility, as in vitro challenge with known agonists (μ: morphine; δ: DPDPE and κ: U 50488) and antagonists (μ: naloxone; δ: naltrindole and κ: nor-binaltrorphimine) showed that the μ-opioid receptor maintained or increased motility while the δ-opioid receptor mediated decreased motility over time. Finally, boar spermatozoa depicted dose-response effects on sperm kinematics and mitochondrial potential following in vitro challenge with 130 pharmacological drugs and toxic compounds as well as with eight known mito-toxic compounds. In conclusion, boar spermatozoa expressing functional water (AQPs-7 and -9) and ion (CatSper 1-4) channels as well as μ- and δ-opioid receptors are able to adapt to stressful environmental variations, capacitation and pharmacological compounds and drug components. Ejaculated sperm suspensions are easily and painlessly obtained from breeding boars, and are suitable biosensors for in vitro drug-induced testing, complying with the 3R principles of reduction and replacement of experimental animals, during early toxicology screening.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. 65 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1526
Keyword
Plasma membrane, membrane channels, membrane receptors, kinematics, 3Rprinciples, spermatozoa, boar.
National Category
Cell and Molecular Biology Pharmacology and Toxicology Cell Biology Pharmaceutical Sciences Biochemistry and Molecular Biology Veterinary Science
Identifiers
urn:nbn:se:liu:diva-131862 (URN)10.3384/diss.diva-131862 (DOI)9789176857267 (ISBN)
Public defence
2016-11-11, Berzeliussalen, Campus US, Linköping, 09:00 (English)
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Supervisors
Available from: 2016-10-11 Created: 2016-10-11 Last updated: 2017-05-29Bibliographically approved

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