Figure 4 |. Windows of vulnerability to environmental reprogramming in spermatogenesis.

The figure shows the stages of spermatogenesis and sperm maturation, highlighting the periods in which environmental exposures can reprogramme epigenetic marks. Active transcription and storage of RNA is ongoing through the spermatogonium, spermatocyte and spermatid stages. However, once compaction of paternal DNA has occurred, which involves replacing the majority of histones with protamines, there is not a clear mechanism by which epigenetic marks can be further altered in the mature sperm. This suggest sthat an environmental exposure must occur within a sensitive time period of spermatogenesis in order to pass on a new or reprogrammed epigenetic mark to future offspring. In most mammals, complete spermatogenesis occurs in 6–8 weeks, by which point sperm are present in the epididymis for final maturation processes. The time between chromatin compaction and the transit of mature sperm to the epididymis is at least 10 days, during which time epigenetic and transcriptional machineries are no longer active. However, the secretion of exosomes and other factors that interact with the maturing sperm in the epididymis may impart lasting epigenetic marks, such as microRNAs. Figure is reproduced from BaleT. Lifetime stress experience: transgenerational epigenetics and germ cell programming. Dialogues Clin. Neurosci. 2014;16:297–305 (REF. 179), with the permission of © AICH-Servier Research Group, Suresnes, France, and adapted from REF. 180, Nature Publishing Group.