Novel identification of peripheral dopaminergic D2 receptor in male germ cells

Abstract

Dopamine is a recognized modulator in the central nervous system (CNS) and peripheral organ functions. The presence of peripheral dopamine receptors outside the CNS has suggested an intriguing interaction between the nervous system and other functional systems, such as the reproductive system. In the present study we analyzed the expression of D2R receptors in rat testis, rat spermatogenic cells and spermatozoa, in different mammals. The RT-PCR analysis of rat testis mRNA showed specific bands corresponding to the two dopamine receptor D2R (L and S) isoforms previously described in the brain. Using Western blot analysis, we confirmed that the protein is present in rat testis, isolated spermatogenic cells and also in spermatozoa of a range of different mammals, such as rat, mouse, bull, and human. The immunohistochemistry analysis of rat adult testis showed that the receptor was expressed in all germ cells (pre-and postmeiotic phase) of the tubule with staining predominant in spermatogonia. Confocal analysis by indirect immunofluorescence revealed that in non-capacitated spermatozoa of rat, mouse, bull, and human, D2R is mainly localized in the flagellum, and is also observed in the acrosomal region of the sperm head (except in human spermatozoa). Our findings demonstrate that the two D2 receptor isoforms are expressed in rat testis and that the receptor protein is present in different mammalian spermatozoa. The presence of D2R receptors in male germ cells implies new and unsuspected roles for dopamine signaling in testicular and sperm physiology.

Light and electron microscopic study on the effect of antischizophrenic drugs on the structure of seminiferous tubules of adult male albino rats

“…However, it has been shown in rats that dopamine receptors are present in germ cells of seminiferous tubules [36,37]. Considering that olanzapine and aripiprazole can bind to these receptors, a direct effect of these drugs on spermatogenesis is possible.…”

“…Therefore, the effects of olanzapine on spermatogenesis may have occurred by two mechanisms: a reduced level of testosterone or a direct action on germ cells. The effect of aripiprazole on spermatogenesis may be attributed to its direct action on germ cells only [37].…”

Involvement of Neurotransmitter and Nrf2 in Nicotine- and Cigarette Smoke-Induced Testicular Toxicity in Adult Rats

“…CA, especially DA, and TH, the DA marker, are found to be important modulators of testis volume, seminiferous epithelium maturation, and spermatogenesis as well as testosterone production. 23,26 DA, BDNF, and oxidative stress also have a potential role in structure-function impairment and total antioxidant depletion in the testicular tissues. 36,82,83 Nicotine further binds with the Rs, hormones, enzymes, etc.…”

“…The presence of DA and DAergic marker, TH, in different testicular tissues further establish the paracrine action of DA in spermatogenesis. 22,[24][25][26] Several previous observations have also shown the positive evidence of brain-testis relation. [27][28][29] Further, regulation of the DAergic development is mediated by other neurotrophic factors, including BDNF, 11 which promotes sprouting of DAergic axons and regulates plasticity of the DAergic neurons.…”

“…22,23 TH, the rate-limiting enzyme of DA (CA) synthesis, is found in Leydig cells, germinal cells, neuron-like cells, and nerve fibers, 24,25 and DA-R is located in neuron-like cells and nerve fibers in human testicular tissue, 24 suggesting paracrine actions of DA in the spermatogenic process. 26 Further, testosterone plays a crucial role in regulation of neural structure and function, modulation of brain circuits at puberty, and regulation of social, risk-taking, and cognitive behavior. 27 Interestingly, brain and testis exhibit maturation relation in terms of development of cerebral cortex and seminiferous epithelium.…”