mTOR Signaling Pathway Regulates Sperm Quality in Older Men.

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.

Preservação da fertilidade masculina no Centro Hospitalar de Vila Nova de Gaia/Espinho EPE - 17 anos de experiência / Preserving male fertility at the Centro Hospitalar de Vila Nova de Gaia/Espinho EPE -17 years of experience

Objetivo. Reportar a nossa experiência nos últimos 17 anos na preservação da fertilidade masculina por doença oncológica, genética, imunológica e endocrinológica, assim como por alterações graves da espermatogénese. Material e métodos. avaliação de parâmetros demográficos, características do esperma e resultados obtidos com amostras descongeladas em ciclos de procriação medicamente assistida (PMA). Resultados. Duzentos e setenta e um homens com uma idade média de 31,5±6,3 anos (16‐52 anos) foram referenciados para PF. A doença oncológica foi a causa mais comum (34,3%), seguida de azoospermia secretora ou não obstrutiva, oligoastenoteratozoospermia (TAO) grave, doença genética, hipogonadismo/atrofia testicular, doença auto‐imune, doença endócrino‐metabólica e pré‐cirurgia potencialmente comprometedora da fertilidade. Dentro da doença oncológica, o tumor do testículo foi a neoplasia mais comum (64,5%), seguido do cancro hematológico e de etiologias variadas. Na doença genética, a síndrome de Klinefelter foi a condição mais frequente (50%). No total 194 homens ficaram com amostras criopreservadas (1.099 amostras no total; 5,7±3,4 por paciente). Os homens com doença oncológica tiveram, em média, um número significativo superior de amostras congeladas (p<0,001). Os casos de tumor do testículo apresentaram uma concentração média de espermatozoides/ml significativamente inferior face aos outros tumores (p<0,005). Durante estes 17 anos, 58 homens (29,9%) procuraram o centro para realização de técnicas de PMA com amostras descongeladas. Foram realizados 87 ciclos, com 19 gestações (21,8%). Nasceram 15 recém‐nascidos (RN) saudáveis. Conclusões. Ainda que o número de homens que tenham procurado o uso das amostras armazenadas, não se pode desvalorizar o impacto psicológico positivo da PF, tendo em conta que pode ser a única possibilidade de paternidade biológica (AU)

Objective. A report is presented of 17 years of experience in male fertility preservation due to oncological, genetic, immunological and endocrinological disease, as well as severe spermatogenesis alterations. Material and methods. An evaluation is made of demographic parameters, sperm characteristics and results of assisted reproduction techniques cycles with thawed samples. Results. A total of 271 men with a mean age 31.5±6.3 years (16 to 52 years) were referred to sperm banking. The most common cause was oncological disease (34.3%), followed by secretory azoospermia, oligoasthenoteratozoospermia, genetic disease, testicular atrophy/hypogonadism, auto‐immune disease, endocrine‐metabolic disease, and prior to potentially fertility damage surgery. Among oncological disease, testicular tumour was the most common cancer (64.5%), followed by haematological cancer, and other aetiologies. Klinefelter syndrome was the most common (50%) among the genetic diseases. A total of 194 men had samples cryopreserved (1099 total samples; 5.7±3.4 per patient). Men with oncological disease had a significantly higher number of cryopreserved samples (p<.001). Testicular tumour cases had a mean lower sperm concentration relative to other tumours (p<.005). During these 17 years, 58 men (29.9%) asked to have assisted reproduction techniques performed with their thawed samples. The 87 cycles performed resulted in 19 pregnancies (21.8%) and 15 healthy newborns. Conclusions. Although the number of men asking to use their cryopreserved samples is low, we cannot undervalue the positive psychological impact of fertility preservation, taking in consideration that it can be the only possibility to biological fatherhood (AU)

Ultraestrutura de um caso de astenozoospermia / Ultrastructure of a case of asthenozoospermia

The article reports the case of a 40-year old man with no history of significant illness. The semen analysis identified total asthenozoospermia. Ultrastructural analysis by electron microscopy showed multiple mitochondrial sheath and flagellum structure anomalies (incomplete/disorganized axoneme, absence of outer dense fibers and fibrous sheath) that explain the sperm immotility. As far as we know, the causes have still not been determined and the possibilities of reproduction involve the use of ICSI with low probability of success (AU)

O artigo apresenta o caso de um paciente de 40 anos sem antecendentes de doenças significativas conhecidas. No espermograma identificou-se astenozoospermia total. Na análise ultraestrutural por microscopia eletrónica de transmissão observaram-se múltiplas nomalias na baínha mitocondrial e na estrutural do flagelo (axonemas incompletos/desorganizados, ausência de fibras densas externas e segmentos de baínha fibrosa) explicativos da imobilidade espermática. As causas da patologia são desconhecidas à luz da ciência atual e as possibilidades de reprodução implicam o recurso à ICSI com baixa probabilidade de sucesso (AU)