Transcription of cAMP and MAPK signaling markers is disturbed in spermatozoa of aged rats

Abstract

According to the World Health Organization, the burden of men (in/sub)fertility remains high, increasing over the years, it is significant, likely underestimated, and has not displayed any decrease over the last 20 years. Besides, an increasing number of unexplained cases of infertile males and a reduction in the fertility rate in men younger than age 30 have been reported. This study was designed to search for the possible markers of decreased spermatozoa functionality during aging. The in vivo experimental models were the aged male rats: 12-month-old-rats (middle-aged; 5 per group), 18-month-old rats (middle-old-age; 5 per group), 22-month-old rats (old-age; 3 per group). The transcriptional profiles of 12 markers of the cAMP signaling pathway and 10 markers of the MAPK signaling pathway were followed in individual spermatozoa samples isolated from the epididymis. The results show that the transcriptions of 83.33% (10/12) cAMP signaling markers and 60% (6/10) MAPK signaling markers were changed during aging. The dominant effect on both signaling pathways was an increase in the levels of transcripts. The most prominent changes (83.33%) in cAMP signaling were observed in the oldest group (22-month-old rats), followed by 70% in 18-month-old rats (middle-old-age) and 66.67% in 12-month-old rats (middle-aged). The levels of transcript for soluble adenylyl cyclase (ADCY10), an enzyme important for capacitation and spermatozoa functionality, significantly increased in spermatozoa obtained from 12-month-old rats (middle-age) and 18-month-old rats (middle-old-age) but decreased in spermatozoa from 22-month-old rats (old-age). Similar patterns were evident following the most prominently expressed catalytic and regulatory subunits of protein kinase A (Prkaca, Prkar1a). The effects were not repeated following the MAPK signaling pathway since 60% of changes were evident in both, the youngest group (12-month-old rats) and the oldest group (22-month-old rats), while in 18-month old rats (middle-old-age) only 30% of changes were observed.