Apelin is found in human sperm and testis and is raised in inflammatory pathological conditions

Moretti, Elena; Signorini, Cinzia; Corsaro, Roberta; Noto, Daria; AntonioTripodi, Sergio; Menchiari, Andrea; Micheli, Lucia; Ponchia, Rosetta; Collodel, Giulia

doi:10.1016/j.cyto.2023.156281

Cited by 6 publications

(6 citation statements)

References 44 publications

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“…Chemerin, apelin, resistin, and visfatin are expressed in the ovaries of various animal species; however, the role of apelin in male reproduction has not yet been clarified [22]. Moretti et al [15] detected increased levels of apelin and IL-1β concentrations in patients' samples with varicocele and infections.…”

Section: Discussionmentioning

confidence: 99%

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Can Dietary n-3 Polyunsaturated Fatty Acids Affect Apelin and Resolvin in Testis and Sperm of Male Rabbits?

Mattioli,

Moretti,

Castellini

et al. 2023

Molecules

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Apelin and other novel adipokines have been associated with normal and pathological reproductive conditions in humans and animals. In this paper, we used a rabbit model to investigate if apelin and resolvin (RvD1) in testis and sperm are associated with the oxidative status of semen and serum testosterone of rabbits fed different diets enriched with flaxseed (alpha-linolenic acid, ALA) or with fish oil (eicosapentaenoic acid, EPA, docosapentaenoic acid, DPAn-3, and docosahexaenoic acid, DHA). Apelin and RvD1 were detected by ELISA and apelin and the apelin receptor by immunofluorescence. Increased levels of apelin in testes from both enriched diets were shown, particularly in the interstitial tissue of the FLAX group. The FLAX diet enhanced serum testosterone, and both enriched diets showed higher levels of malondialdehyde and RvD1 in the testis. In ejaculated sperm, apelin and its receptor were localized in the entire tail of the control and both treated groups. The ryanodine receptor was investigated in rabbit testis; the fluorescent signal was increased in mature elongated spermatids of the FLAX group. In conclusion, this data seems to indicate that FLAX increases the amount of apelin in testis, suggesting an involvement of this adipokine in male reproduction and probably a role in the resolution of the inflammatory status.

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Section: Discussionmentioning

confidence: 99%

“…Recently apelin/APJ-R system has been localized in human spermatozoa and testicular tissue and is probably involved in human fertility [15].…”

Section: Introductionmentioning

confidence: 99%

Can Dietary n-3 Polyunsaturated Fatty Acids Affect Apelin and Resolvin in Testis and Sperm of Male Rabbits?

Mattioli,

Moretti,

Castellini

et al. 2023

Molecules

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“…In this paper, we evaluated the role of NGF and its receptors in the sperm, testis and epididymis of fertile men and men with infertility due to varicocele or a UGI. The main pathological features of varicocele and UGIs are associated with oxidative stress and the inflammatory status of the reproductive apparatus [43,49]. Previous studies in humans and various animal species have analysed the role of seminal NGF on sperm [19,20,29].…”

Section: Discussionmentioning

confidence: 99%

“…Seminal F 2 -isoprostanes (F 2 -IsoPs), a class of IsoPs, are considered a marker of sperm immaturity in semen from infertile patients with varicocele [42]. Moreover, interleukin 1β (Il-1β) may be considered a marker of inflammatory reproductive pathologies [43].…”

Section: Introductionmentioning

confidence: 99%

A Possible Role for Nerve Growth Factor and Its Receptors in Human Sperm Pathology

Stabile,

Pistilli,

Moretti

et al. 2023

Biomedicines

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Nerve growth factor (NGF) signalling affects spermatogenesis and mature sperm traits. In this paper, we aimed to evaluate the distribution and the role of NGF and its receptors (p75NTR and TrKA) on the reproductive apparatus (testis and epididymis) and sperm of fertile men (F) and men with different pathologies, namely varicocele (V) and urogenital infections (UGIs). We collected semen samples from 21 individuals (31–40 years old) subdivided as follows: V (n = 7), UGIs (n = 7), and F (n = 7). We submitted the semen samples to bacteriological analysis, leucocyte identification, and analysis of sperm parameters (concentration, motility, morphology, and viability). We determined the seminal plasma levels of NGF, interleukin 1β (IL-1β), and F2-isoprostanes (F2-IsoPs), and the gene and protein expression of NGF receptors on sperm. We also used immunofluorescence to examine NGF receptors on ejaculated sperm, testis, and epididymis. As expected, fertile men showed better sperm parameters as well as lower levels of NGF, F2-IsoPs, and IL-1β compared with men with infertility. Notably, in normal sperm, p75NTR and TrKA were localised throughout the entire tail. TrKA was also found in the post-acrosomal sheath. This localisation appeared different in patients with infertility: in particular, there was a strong p75NTR signal in the midpiece and the cytoplasmic residue or coiled tails of altered ejaculated sperm. In line with these findings, NGF receptors were intensely expressed in the epididymis and interstitial tissue of the testis. These data suggest the distinctive involvement of NGF and its receptors in the physiology of sperm from fertile men and men with infertility, indicating a possible role for new targeted treatment strategies.

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“…Among these cytokines, IL-6, IL-1β, and TNF-α play a pivotal role in provoking testicular impairment [53,61]. Notably, IL-1β assumes a central role within the cascade of inflammatory responses and can be considered a biomarker for inflammatory reproductive disorders [62,63], while TNF-α originating from germ cells facilitates testicular detriment through the inflammatory pathways, concurrently dictating the modulation of germ cell apoptosis [64]. Research findings demonstrate that positive expression of proinflammatory cytokines such as IL-6, IL-8, and TNF-α substantially increased within the liver and kidney of the model, as illustrated in Fig 2E . This highlights that CRS and adenine yield a deleterious influence on the organism's immune system, thereby leading to an insufficient regulatory capacity of the liver and kidney towards inflammatory responses, consequently afflicting the testes with damage and perturbing germinal function.…”

Section: Plos Onementioning

confidence: 99%

Exploring pathogenesis and biomarkers through establishment of a rat model of male infertility with liver depression and kidney deficiency

Shen,

Fan,

Liu

et al. 2024

PLoS ONE

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Objectives To establish a rat model that accurately replicates the clinical characteristics of male infertility (MI) with Liver Depression and Kidney Deficiency (LD & KD) and investigate the pathogenesis. Methods After subjecting the rats to chronic restraint stress (CRS) and adenine treatment, a series of tests were conducted, including ethological assessments, evaluations of reproductive characteristics, measurements of biochemical parameters, histopathological examinations, and analyses of urinary metabolites. Additionally, bioinformatics predictions were performed for comprehensive analysis. Results Compared to the control, the model exhibited significant manifestations of MI with LD & KD, including reduced responsiveness, diminished frequency of capturing estrous female rats, and absence of mounting behavior. Additionally, the kidney coefficient increased markedly, while the coefficients of the testis and epididymis decreased significantly. Sperm counts and viabilities decreased notably, accompanied by an increase in sperm abnormalities. Dysregulation of reproductive hormone levels in the serum was observed, accompanied by an upregulation of proinflammatory cytokines expressions in the liver and kidney, as well as exacerbated oxidative stress in the penile corpus cavernosum and testis. The seminiferous tubules in the testis exhibited a loose arrangement, loss of germ cells, and infiltration of inflammatory cells. Furthermore, utilizing urinary metabolomics and bioinformatics analysis, 5 key biomarkers and 2 crucial targets most closely linked to MI were revealed. Conclusion The study successfully established a clinically relevant animal model of MI with LD & KD. It elucidates the pathogenesis of the condition, identifies key biomarkers and targets, and provides a robust scientific foundation for the prediction, diagnosis, and treatment of MI with LD & KD.

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Apelin is found in human sperm and testis and is raised in inflammatory pathological conditions

Cited by 6 publications

References 44 publications

Can Dietary n-3 Polyunsaturated Fatty Acids Affect Apelin and Resolvin in Testis and Sperm of Male Rabbits?

Can Dietary n-3 Polyunsaturated Fatty Acids Affect Apelin and Resolvin in Testis and Sperm of Male Rabbits?

A Possible Role for Nerve Growth Factor and Its Receptors in Human Sperm Pathology

Exploring pathogenesis and biomarkers through establishment of a rat model of male infertility with liver depression and kidney deficiency

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