Seminal angiotensin II as a predictive factor of spermatogenic activity in non-obstructive azoospermia

Angiotensina II seminal como factor predictivo de la actividad espermatogénica en azoospermia no obstructiva

Background: There is an unmet need for a non-invasive marker to predict spermatogenic potential and the likelihood of finding mature sperm in cases of non-obstructive azoospermia (NOA). Accordingly, we assessed the level of seminal angiotensin II (Ang II), which is suggested to be linked to sperm motility and count, and its relation to spermatogenic activity. Methods: A prospective case-control study included three groups: Group I, consisting of 30 male patients with NOA; Group II, consisting of 30 male patients with obstructive azoospermia (OA); and Group III, consisting of 30 healthy fertile males as the control group. Results: Seminal Ang II levels were significantly lower in OA patients compared to NOA patients (p < 0.001) and controls (p < 0.001). Additionally, angiotensin II levels were significantly lower among NOA patients than controls (p < 0.001). In NOA patients, the lowest Ang II average was observed in those with Sertoli cell-only syndrome (SCO) and the highest in those with late maturation arrest (p ≤ 0.05). Conclusions: Our findings suggested that seminal Ang II may serve as a predictive marker for spermatogenesis and the presence of mature sperm in microsurgical testicular sperm extraction (micro-TESE) in cases of non-obstructive azoospermia.

Resumen

Antecedentes: Existe una necesidad insatisfecha de un marcador no invasivo para predecir el potencial espermatogénico y la probabilidad de encontrar espermatozoides maduros en casos de azoospermia no obstructiva (ANO). En consecuencia, evaluamos el nivel de angiotensina II seminal (Ang II), que se sugiere está vinculada con la motilidad y el conteo de espermatozoides, y su relación con la actividad espermatogénica. Métodos: Se realizó estudio prospectivo de casos y controles incluyó tres grupos: Grupo I, compuesto por 30 pacientes masculinos con ANO; Grupo II, compuesto por 30 pacientes masculinos con azoospermia obstructiva (AO); y Grupo III, compuesto por 30 hombres fértiles saludables como grupo control. Resultados: Los niveles de angiotensina II seminal fueron significativamente más bajos entre los pacientes con AO en comparación con los pacientes con ANO (p < 0.001) y controles (p < 0.001). Además, los niveles de angiotensina II fueron significativamente más bajos entre los pacientes con ANO que entre los controles (p < 0.001). En los pacientes con ANO, el promedio más bajo de Ang II se observó en aquellos con síndrome de células de Sertoli únicamente (SCO) y el más alto en aquellos con detención de maduración tardía (p ≤ 0.05). Conclusiones: Nuestros hallazgos sugieren que la Ang II seminal podría servir como un marcador predictivo de la espermatogénesis y la presencia de espermatozoides maduros en la extracción de espermatozoides testiculares mediante microscirugía (micro-TESE) en casos de azoospermia no obstructiva.

Azoospermia; Non-obstructive; Angiotensin II; Spermatogenic activity

Palabras Clave

Azoospermia; No obstructiva; Angiotensina II; Actividad espermatogénica

[1] Ali NH, Jewad AM, Attayia AK. Investigate the seminal plasma biomarkers in differentiation between obstructive-and non-obstructive azoospermia. Maaen Journal for Medical Sciences. 2022; 1: 47–52.

[2] Andrade DL, Viana MC, Esteves SC. Differential diagnosis of azoospermia in men with infertility. Journal of Clinical Medicine. 2021; 10: 3144.

[3] Arrighi N. Chapter 16: surgical management of male infertility and sperm retrieval. In Laganà AS and Guglielmino A (eds.) Management of Infertility (pp. 155–163). 2nd edition. Academic Press: San Diego, CA. 2023.

[4] Moustakli E, Zikopoulos A, Skentou C, Stavros S, Sofikitis N, Georgiou I, et al. Integrative assessment of seminal plasma biomarkers: a narrative review bridging the gap between infertility research and clinical practice. Journal of Clinical Medicine. 2024; 13: 3147.

[5] O’Mahony OA, Djahanbahkch O, Mahmood T, Puddefoot JR, Vinson GP. Angiotensin II in human seminal fluid. Human Reproduction. 2000; 15: 1345–1349.

[6] Gianzo M, Subirán N. Regulation of male fertility by the renin-angiotensin system. International Journal of Molecular Sciences. 2020; 21: 7943.

[7] Edenfield RC, Easley CA 4th. Implications of testicular ACE2 and the renin-angiotensin system for SARS-CoV-2 on testis function. Nature Reviews Urology. 2022; 19: 116–127.

[8] Porstmann T, Kiessig ST. Enzyme immunoassay techniques. An overview. Journal of Immunological Methods. 1992; 150: 5–21.

[9] Untan I. Coexistence of leydig cell tumour and sertoli cell-only syndrome with an incompatible hormone profile and azoospermia. Acta Endocrinologica. 2023; 19: 252–255.

[10] El-Ariny AF, El-Garem YF, Eid AA, Donia HM, Aly RG, Abdelmeniem IM. Seminal levels of angiotensin II and angiotensin II type 2 receptor expression on spermatozoa in varicocele patients: relation to fertility status. Andrologia. 2020; 52: e13513.

[11] Zhang F, Dai M, Yang X, Cheng Y, Ye L, Huang W, et al. Predictors of successful salvage microdissection testicular sperm extraction (mTESE) after failed initial TESE in patients with non-obstructive azoospermia: a systematic review and meta-analysis. Andrology. 2024; 12: 30–44.

[12] Huang IS, Huang WJ, Lin AT. Distinguishing non-obstructive azoospermia from obstructive azoospermia in Taiwanese patients by hormone profile and testis size. Journal of the Chinese Medical Association. 2018; 81: 531–535.

[13] Schoor RA, Elhanbly S, Niederberger CS, Ross LS. The role of testicular biopsy in the modern management of male infertility. Journal of Urology. 2002; 167: 197–200.

[14] Shamohammadi I, Sadighi Gilani M, Kazemeyni SM, Hasanzadeh T, Vosough Taqi Dizaj A, Dizavi A. Evaluation of azoospermic patients to distinguish obstructive from non-obstructive azoospermia, and necessity of diagnostic testis biopsy: a retrospective study. International Journal of Fertility and Sterility. 2022; 16: 156–161.