Exploring the Stress Impact in the Paternal Germ Cells Epigenome: Can Catecholamines Induce Epigenetic Reprogramming?

Abstract

Spermatogenesis is characterized by unique epigenetic programs that enable chromatin remodeling and transcriptional regulation for proper meiotic divisions and germ cells maturation. Paternal lifestyle stressors such as diet, drug abuse, or psychological trauma can directly impact the germ cell epigenome and transmit phenotypes to the next generation, pointing to the importance of epigenetic regulation during spermatogenesis. It is established that environmental perturbations can affect the development and behavior of the offspring through epigenetic inheritance, including changes in small non-coding RNAs, DNA methylation, and histones post-translational modifications. But how male germ cells react to lifestyle stressors and encode them in the paternal epigenome is still a research gap. Most lifestyle stressors activate catecholamine circuits leading to both acute and long-term changes in neural functions, and epigenetic mechanisms show strong links to both long-term and rapid, dynamic gene expression regulation during stress. Importantly, the testis shares a molecular and transcriptional signature with the brain tissue, including a rich expression of catecholaminergic elements in germ cells that seem to respond to stressors with similar epigenetic and transcriptional profiles. In this minireview, we put on stage the action of catecholamines as possible mediators between paternal stress responses and epigenetic marks alterations during spermatogenesis. Understanding the epigenetic regulation in spermatogenesis will contribute to unravel the coding mechanisms in the transmission of the biological impacts of stress between generations.

Impact of stress on male fertility: role of gonadotropin inhibitory hormone

“…Stress is an important phenomenon for survival that requires prompt physiological and behavioral responses for an individual to cope with the different situations in the environment and maintain body homeostasis ( 27 ). Physiologically, stress response can be categorized into the fast response mediated by the sympathoneural and sympathoadrenomedullary (SAM) axis and the slow response mediated by the hypothalamic-pituitary-adrenal axis (HPA) ( 28 ).…”

“…In addition, the activation of the first line of the stress response stimulates the slow response, which is mediated by the activation of the HPA axis to release glucocorticoids ( 28 ). Corticotropin-releasing hormone (CRH) is secreted from the paraventricular nucleus (PVN) of the hypothalamus and binds to its receptors (CRH-R1 and CRH-R2).…”

“…The interplay between sympathoneural, SAM, and HPA axis in response to stress systematically produces metabolic and behavioral changes that are transient and adaptive ( 28 ). However, chronic sympathetic discharge and elevated levels of glucocorticoid during prolonged stress are associated with pathological conditions, such as metabolic disorder and infertility.…”

The Potential Role of PPARs in the Fetal Origins of Adult Disease

“…Prenatal stress exposure has been linked to neurodevelopment and the risk of neuropsychiatric disorders in offspring [ 79 ]. Retrospective epidemiological studies have provided compelling evidence linking lifetime stress exposure in men with disease risk in offspring [ 80 ]. The rodent studies have demonstrated the susceptibility of germ cells to stressful environments throughout the paternal lifetime [ 81 ].…”

Metabolic Profiles and Sperm Production in Imported Holstein Bull Sires Under Different Climatic and Geochemical Conditions of Russia and Kazakhstan

“…Качество семени зависит от физиологического статуса самца и определяет его роль в воспроизводстве потомства, которая не ограничивается собственно оплодотворением самки. Выяснено, что характер реакции на стресс в следующем поколении определяется девятью видами микроРНК (miRNA), которые присутствуют в сперме (35,36). Изменения, вызванные внешними факторами, наследуются от отцов через метилирование ДНК сперматозоидов, модификацию белков, участвующих в упаковке ДНК, а также через эпигенетические модификации, вызванные изменением состава и структуры РНК, содержащейся в сперме, следовательно, самцы, находящиеся в хроническом стрессе, производят потомство со значительно ослабленной стрессовой реакцией во взрослом возрасте (37).…”