Please use this identifier to cite or link to this item: http://hdl.handle.net/10773/29213
Title: mTOR signaling pathway regulates sperm quality in older men
Author: Silva, Joana Vieira
Cabral, Madalena
Correia, Bárbara Regadas
Carvalho, Pedro
Sousa, Mário
Oliveira, Pedro Fontes
Fardilha, Margarida
Keywords: Aging
Sperm quality
Signaling proteins
mTORC1
TP53
Issue Date: Jun-2019
Publisher: MDPI
Abstract: Understanding how age affects fertility becomes increasingly relevant as couples delay childbearing toward later stages of their lives. While the influence of maternal age on fertility is well established, the impact of paternal age is poorly characterized. Thus, this study aimed to understand the molecular mechanisms responsible for age-dependent decline in spermatozoa quality. To attain it, we evaluated the impact of male age on the activity of signaling proteins in two distinct spermatozoa populations: total spermatozoa fraction and highly motile/viable fraction. In older men, we observed an inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) in the highly viable spermatozoa population. On the contrary, when considering the entire spermatozoa population (including defective/immotile/apoptotic cells) our findings support an active mTORC1 signaling pathway in older men. Additionally, total spermatozoa fractions of older men presented increased levels of apoptotic/stress markers (e.g., cellular tumor antigen p53-TP53) and mitogen-activated protein kinases (MAPKs) activity. Moreover, we established that the levels of most signaling proteins analyzed were consistently and significantly altered in men more than 27 years of age. This study was the first to associate the mTOR signaling pathway with the age impact on spermatozoa quality. Additionally, we constructed a network of the sperm proteins associated with male aging, identifying TP53 as a central player in spermatozoa aging.
Peer review: yes
URI: http://hdl.handle.net/10773/29213
DOI: 10.3390/cells8060629
ISSN: 2073-4409
Appears in Collections:IBIMED - Artigos
DCM - Artigos

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