Can proteomic analysis help us understand the molecular events in men with idiopathic germ cell aplasia?

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Volume 111, Issue 4, Page 671

Authors:

Himanshu Arora, Ph.D.

Abstract:

Reflections on "Impaired testicular signaling of vitamin A and vitamin K contributes to the aberrant composition of the extracellular matrix in idiopathic germ cell aplasia" by Alfano et al.


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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

1 Comments

Go to the profile of Alfano Massimo
Alfano Massimo over 1 year ago

We thank Dr. Arora for his insightful comment to our publication (1). We agree that retinoic acid (RA) has been shown to play a key role in steroidogenesis, spermatogonial proliferation and the initiation of meiosis in the adult gonads (2-7); conversely, little is known about the effect of RA on the modulation of the human testis extracellular matrix (ECM). More in details, it is a novel finding of our study that the increased RA signaling in the Sertoli cells is a feature associated with complete idiopathic germ cell aplasia, despite normal systemic levels of retinol. This piece of information would suggest that treating infertile men with retinoic acid to improve spermatogenesis (8) might be tricky. Similarly, several authors already pointed out that either a deficit or an excess of RA resulted in testicular lesions and spermatogenetic disorders thus contributing to testicular dysgenesis syndrome (9-12).


Second novelty from our study is the association between the increased RA signaling of Sertoli cells and the decreased levels of expression of few of the basal membrane components (i.e., HSPG2 and NID2) of the seminiferous tubules in idiopathic germ cell aplasia. Moreover, we showed for the first time a decreased signaling of vitamin K in Leydig cells, which was associated with the decreased level of the ECM regulator Factor IX. Altogether, these novel findings highlight the relevance of vitamin A and vitamin K signaling in the process of modulation of the testis ECM composition in idiopathic germ cell aplasia, regardless of the systemic levels of those two vitamins.


From a pathophysiological standpoint, our study provides novel insights in terms of the dysregulation of the human testicular microenvironment in idiopathic germ cell aplasia, identifying the potential role of a local impairment of vitamin A and K metabolic pathways in men with non-obstructive azoospermia. Thereof, as it has been correctly stated by Dr. Arora in his editorial, we actually hope that our findings can help in the identification of non-invasive, clinically useful biomarkers and new therapeutic targets for non-obstructive azoospermic patients.


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Alfano Massimo, Pederzoli Filippo, Salonia Andrea