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Review
. 2024 Aug 28;13(17):5097.
doi: 10.3390/jcm13175097.

The Smoky Impact of Nicotinic Acetylcholine Receptors on Testicular Function

Federica Barbagallo  1 , Maria Rita Assenza  1 , Filippo Torrisi  1 , Alessandra Buonacquisto  1 , Francesco Pallotti  1   2
Affiliations
Review

The Smoky Impact of Nicotinic Acetylcholine Receptors on Testicular Function

Federica Barbagallo et al. J Clin Med. .

Abstract

Smoking habits (from classic cigarettes to e-cigarettes and heated tobacco) are a relatively common finding in the medical histories of couples referred to fertility centers. Tobacco smoke and e-cigarettes may deliver many substances with known harmful effects on both general and reproductive health, including nicotine. Nicotinic Acetylcholine receptors (nAChRs) form a heterogeneous family of ion channels that are differently expressed in different tissues. According to the homomeric or heteromeric combination of at least five different subunits (named from α to ε), they have peculiar pharmacological and biophysical properties. nAChRs respond to the neurotransmitter acetylcholine, which influences a number of physiological functions not restricted to neurons and plays an important role in the structure and function of non-neuronal tissues such as the testis. nAChRs are also the target of Nicotine, the active element responsible for tobacco addiction. This review summarizes recent findings on the involvement of nAChRs in testicular physiology, highlighting the effects of nicotine exposure observed in animal studies and clinical settings. We will discuss the latest data on fertility outcomes and the implications for understanding nAChR functions in reproductive health.

Keywords: Leydig cells; Sertoli cells; cigarette smoking; male fertility; nicotine; nicotinic receptors; spermatogenesis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic representation of spermatogenesis and spermiogenesis. Spermatogenesis takes place within the seminiferous tubules of the testes. Near the basal lamina (blue curved line), diploid primordial germ cells (spermatogonia) undergo mitosis, producing diploid primary spermatocytes. Primary spermatocytes move towards the lumen of the seminiferous tubules and begin meiosis I, resulting in haploid secondary spermatocytes. These secondary spermatocytes undergo meiosis II to produce haploid spermatids. Mature sperm cells (spermatozoa) develop from spermatids through spermiogenesis. Leydig cells, which produce testosterone, and a microvessel are located in the interstitial space. Sertoli cells form the blood–testis barrier (BTB), the tightest blood–tissue barrier in the mammalian body. Leydig and Sertoli cells create the cellular and hormonal environment necessary for spermatozoa development (created with BioRender.com).
Figure 2
Figure 2
The figure summarizes the known effects of tobacco products on semen quality. Tobacco smoke is known to increase the formation of reactive oxygen species (ROS), leading to oxidative stress. The excessive buildup of ROS causes lipid peroxidation and DNA strand breaks, resulting in altered sperm parameters and functions. This increase in ROS levels can also trigger apoptosis by raising the levels of pro-apoptotic cytokines, which further contributes to sperm DNA damage and impaired male fertility. Furthermore, tobacco smoke has been shown to decrease nuclear protamine levels and protamination (created with BioRender.com).
Figure 3
Figure 3
Summary representation of main known effects of nicotine on testicular function (created with BioRender.com, accessed on 21 August 2024).
See this image and copyright information in PMC

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