Male reproductive health and intergenerational metabolic responses from a small RNA perspective

• Published in: Journal of internal medicine Vol. 288; no. 3; pp. 305 - 320
• Main Authors: Nätt, D., Öst, A.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-09-2020
• Subjects: Animal models; cell biology; Diabetes mellitus; diet; Epididymis; Epigenesis, Genetic; epigenetic inheritance; Humans; Infertility; Male; Metabolic disorders; Metabolic response; Metabolic syndrome; Metabolic Syndrome - genetics; Metabolism; Mitochondria; Obesity; Offspring; Paternal Inheritance; Physical exercise; reproduction; Reproductive Health; RNA, Small Untranslated - genetics; rRNA; small RNA; Sperm; Sperm Count; Sperm Motility; Spermatogenesis; Spermatogenesis - genetics; Spermatozoa; tRNA; metabolic syndrome; cell biology; sperm motility; sperm; diet; small RNA; infertility; epigenetic inheritance; obesity; reproduction
• ISSN: 0954-6820; 1365-2796; 1365-2796
• DOI: 10.1111/joim.13096

The world has recently experienced a decline in male reproductive (e.g. sperm counts and motility) and metabolic (e.g. obesity and diabetes) health. Accumulated evidence from animal models also shows that the metabolic health of the father may influence the metabolic health in his offspring. Vectors for such paternal intergenerational metabolic responses (IGMRs) involve small noncoding RNAs (sncRNAs) that often increase in spermatozoa during the last days of maturation in the epididymis. We and others have shown that the metabolic state – depending on factors such as diet, obesity and physical exercise – may affect sperm quality and sperm sncRNA. Together, this suggests that there are overlapping aetiologies between the male metabolic syndrome, male factor infertility and intergenerational responses. In this review, we present a theoretical framework for an overlap of these aetiologies by exploring the advances in our understanding of the roles of sncRNA in spermatogenesis and offspring development. A special focus will lie on novel findings about tRNA‐derived small RNA (tsRNA), rRNA‐derived small RNA (rsRNA) and small mitochondrial RNA (mitoRNA), and their emerging roles in intergenerational metabolic and reproductive health.