Male fertility is in significant decline across the western world. Consequently, the proportion of men requiring fertility treatment has risen from 12.4% in 2004 to 21.3% in 2017. The largest “diagnosed” cause of impaired male fertility is attributed to a combination of low sperm count, poor motility and abnormal morphology and is clinically known as Oligoasthenoteratozoospermia (OAT). The testis typically run at 3-4oC lower than core body temperature. Remarkably, testicular hyperthermia is known to be a major cause of OAT, with a 1°C increase median scrotal temperature enough to cause a 40% reduction in sperm concentration in men. Testicular hyperthermia does not affect all cell but rather appears to be specific to pachytene spermatocytes and round spermatids.
To better understand the initial transcriptomic changes that result from testicular hypothermia we performed Next Generation RNA sequencing on round spermatids isolated from male CD1 mice (N=5) subject to testicular heat stress (42°C, 30min) versus controls (30°C, 30min). From this data we identified two key findings
Firstly, the significant upregulation of anti-apototic HSPA1A is attenuated in heat stress round spermatids compared to somatic cells which could countribute to their high sensitivity to heat stress. Secondly we identified two novel, testis specific long non-coding (LNC) RNAs that are unpregulated in response to testicular heating. Independent over expression of both LNC-RNAs leads to increased cell death in somaic cell lined in vitro. Work is continuing to better understand the molecular mechanisms behind both of these key findings