Physiological and pharmacological aspects of the vas deferens—an update

Koslov, David; Andersson, Karl‐Erik

doi:10.3389/fphar.2013.00101

Cited by 50 publications

(43 citation statements)

References 131 publications

(161 reference statements)

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“…Since contractility of the vas deferens is important for proper ejaculation, drugs that interfere with muscular contraction (notably, α-adrenergic blockers) may cause side effects that interfere with patient compliance [29]. Drug transporters expressed in the vas deferens such as Oct1, Oct3, OctN2, and Oatp1a4 can affect the distribution of xenobiotics into the vas deferens and thus potentiate undesirable side effects for several drugs.…”

Section: Discussionmentioning

confidence: 99%

Xenobiotic transporter expression along the male genital tract

Klein

Wright

Cherrington

2014

Reproductive Toxicology

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The male genital tract plays an important role in protecting sperm by forming a distinct compartment separate from the body which limits exposure to potentially toxic substrates. Transporters along this tract can influence the distribution of xenobiotics into the male genital tract through efflux back into the blood or facilitating the accumulation of toxicants. The aim of this study was to quantitatively determine the constitutive mRNA expression of 30 xenobiotic transporters in caput and cauda regions of the epididymis, vas deferens, prostate, and seminal vesicles from adult Sprague-Dawley rats. The epididymis was found to express at least moderate levels of 18 transporters, vas deferens 15, seminal vesicles 23, and prostate 18. Constitutive expression of these xenobiotic transporters in the male genital tract may provide insight into the xenobiotics that can potentially be transported into these tissues and may provide the molecular mechanism for site specific toxicity of select agents.

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Section: Discussionmentioning

confidence: 99%

Xenobiotic transporter expression along the male genital tract

Klein

Wright

Cherrington

2014

Reproductive Toxicology

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Section: Male Reproductive Tractmentioning

confidence: 99%

“…The vas deferens transports sperm to the seminal vesicles and other ejaculatory glands prior to expulsion via the urethra (43). The vas deferens is lined with epithelium which further concentrate sperm and functions to propel (43), and accessory ejaculatory glands (seminal vesicles, bulbourethral gland, and prostate) add protective seminal plasma and activation factors, which promote further capacitation of the sperm to support fertilization. The prostate gland produces 30% of the ejaculate and is a common site of cancerous transformation in later life, development of which is thought to be androgen-dependent (44), and thus is treated with anti-androgen therapy (45).…”

Section: Male Reproductive Tractmentioning

confidence: 99%

Microphysiological modeling of the reproductive tract: A fertile endeavor

Eddie

Kim

Woodruff

et al. 2014

Exp Biol Med (Maywood)

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Preclinical toxicity testing in animal models is a cornerstone of the drug development process, yet it is often unable to predict adverse effects and tolerability issues in human subjects. Species-specific responses to investigational drugs has led researchers to utilize human tissues and cells to better estimate human toxicity. Unfortunately, human cell-derived models are imperfect because toxicity is assessed in isolation, removed from the normal physiologic microenvironment. Microphysiological modeling, often referred to as ‘organ-on-a-chip’ or ‘human-on-a-chip’ places human tissue into a microfluidic system that mimics the complexity of human in vivo physiology, thereby allowing for toxicity testing on several cell types, tissues, and organs within a more biologically relevant environment. Here we describe important concepts when developing a repro-on-a-chip model. The development of female and male reproductive microfluidic systems is critical to sex-based in vitro toxicity and drug testing. This review addresses the biological and physiological aspects of the male and female reproductive systems in vivo and what should be considered when designing a microphysiological human-on-a-chip model. Additionally, interactions between the reproductive tract and other systems are explored, focusing on the impact of factors and hormones produced by the reproductive tract and disease pathophysiology.

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“…Stimulation of sympathetic nerves in the vas deferens leads to a classical biphasic contractile response, composed of an initial transient contraction, sometimes referred to as a “twitch” contraction followed by a secondary sustained contraction, known as the “hump” contraction. The transient response is brought about by activation of postjunctional P 2 X receptors by ATP, whereas the secondary component involves activation of postjunctional α 1 -adrenoceptors by NA (Ventura 1998; Burnstock and Verkhratsky 2010; Koslov and Andersson 2013). …”

Section: Introductionmentioning

confidence: 99%

“…The vas deferens also contains a rich population of cholinergic nerves (Furness and Iwayama 1972; Gosling and Dixon 1972; Majcen 1984), although their precise role and contribution to the biphasic contractions described above remains unclear (Koslov and Andersson 2013). This is partly due to conflicting reports in the literature.…”

Section: Introductionmentioning

confidence: 99%

Regulation of nerve-evoked contractions of rabbit vas deferens by acetylcholine

et al. 2015

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Stimulation of intramural nerves in the vas deferens of many species yields a classical biphasic contraction comprised of an initial fast component, mediated by P2X receptors and a second slower component, mediated by α1-adrenoceptors. It is also recognized that sympathetic nerve-mediated contractions of the vas deferens can be modulated by acetylcholine (Ach), however there is considerable disagreement in the literature regarding the precise contribution of cholinergic nerves to contraction of the vas deferens. In this study we examined the effect of cholinergic modulators on electric field stimulation (EFS)-evoked contractions of rabbit vas deferens and on cytosolic Ca2+ levels in isolated vas deferens smooth muscle cells (VDSMC). The sustained component of EFS-evoked contractions was inhibited by atropine and by the selective M3R antagonist, 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP). EFS-evoked contractions were potentiated by Ach, carbachol (Cch), and neostigmine. The sustained phase of the EFS-evoked contraction was inhibited by prazosin, an α1-adrenoceptor antagonist and guanethidine, an inhibitor of noradrenaline release, even in the continued presence of Ach, Cch or neostigmine. The soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one enhanced the amplitude of EFS-evoked contractions and reduced the inhibitory effects of 4-DAMP. Isolated VDSMC displayed spontaneous Ca2+ oscillations, but did not respond to Cch. However, the α1-adrenoceptor agonist, phenylephrine, evoked a Ca2+ transient and contracted the cells. These data suggest that EFS-evoked contractions of the rabbit vas deferens are potentiated by activation of M3 receptors and reduced by activation of a sGC-dependent inhibitory pathway.

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Physiological and pharmacological aspects of the vas deferens—an update

Cited by 50 publications

References 131 publications

Xenobiotic transporter expression along the male genital tract

Xenobiotic transporter expression along the male genital tract

Microphysiological modeling of the reproductive tract: A fertile endeavor

Regulation of nerve-evoked contractions of rabbit vas deferens by acetylcholine

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