Proteomics

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Protein composition of the extracellular matrix in idiopathic germ cell aplasia

ABSTRACT: The somatic microenvironment supports spermatogonial stem cell differentiation into sperm. Extracellular matrix (ECM) plays multiple roles in the stem cell niche, including self-renewal, proliferation, differentiation and survival of spermatogonial cells. The pathophysiology of male infertility might be representative of a progressive degenerative process of the testicular tissue, including ECM, rather than a defective genetic background, thus outlining the existence of chronic etiological agents/pathways. In this context, we sought to identify potential causative factors responsible for a number of modifications of the testicular somatic microenvironment associated with idiopathic germ cell aplasia in human beings. Proteomic analysis of the decellularized ECM was performed to study testis parenchyma from 10 idiopathic non-obstructive azoospermic (iNOA) men, dichotomized according to positive sperm retrieval versus germ cell aplasia. Germ cell aplasia was characterized by an increased nuclear distribution of the retinoic acid receptor in Sertoli cells which was associated with decreased expression of the ECM markers, Nidogen-2 and Heparan sulfate proteoglycan-2. Decreased levels of the interstitial matrisome associated Factor IX and its regulator VKORC1 were instead coupled with decreased signaling of vitamin K in Leydig cells. This study identified pathogenetic signature of the somatic testicular microenvironment and provide mechanistic insights into the molecular determinants of human idiopathic germ cell aplasia.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Testis

SUBMITTER: Annapaola Andolfo  

LAB HEAD: Massimo Alfano

PROVIDER: PXD011817 | Pride | 2019-01-07

REPOSITORIES: Pride

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Impaired testicular signaling of vitamin A and vitamin K contributes to the aberrant composition of the extracellular matrix in idiopathic germ cell aplasia.

Alfano Massimo M   Pederzoli Filippo F   Locatelli Irene I   Ippolito Silvia S   Longhi Erika E   Zerbi Pietro P   Ferrari Maurizio M   Brendolan Andrea A   Montorsi Francesco F   Drago Denise D   Andolfo Annapaola A   Nebuloni Manuela M   Salonia Andrea A  

Fertility and sterility 20190401 4

<h4>Objective</h4>To study pathogenic features of the somatic testicular microenvironment associated with idiopathic germ cell aplasia.<h4>Design</h4>Cross-sectional study.<h4>Setting</h4>Tertiary referral center for reproductive medicine.<h4>Patient(s)</h4>Testicular specimens from men with idiopathic nonobstructive azoospermia (iNOA) prospectively submitted to microdissection testicular sperm extraction. Of 20 specimens used for histology, 10 were also available for proteomic analysis. Primary  ...[more]

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