Thyroid hormone action in the developing testis: intergenerational epigenetics.

Document Type

Article

Publication Date

1-1-2020

Institution/Department

Center for Molecular Medicine, Maine Medical Center Research Institute

Journal Title

The Journal of endocrinology

MeSH Headings

Male, Testis, Thyroid Hormones, Epigenomics, Epigenesis, Genetic, Sex Differentiation

Abstract

Male fertility involves the successful transmission of the genetic code to the next generation. It requires appropriately timed cellular processes during testis development, adequate support of spermatogenesis by hormonal cues from the reproductive axis and cellular cross-talk between germ and somatic cells. In addition to being the vessel of the father's genome, increasing evidence shows that the mature sperm carries valuable epigenetic information - the epigenome - that, after fecundation, influences the development of the next generation, affecting biological traits and disease susceptibility. The epigenome of the germ line is susceptible to environmental factors, including exogenous chemicals and diet, but is also affected by endogenous molecules and pathophysiological conditions. Factors affecting testis development and the epigenetic information of the germ line are critical for fertility and of relevance to the non-genetic but heritable component in the etiology of complex conditions. Thyroid hormones are one of those factors and their action, when untimely, produces profound effects on the developing testis, affecting spermatogenesis, steroidogenesis, testis size, reproductive hormones and fertility. Altered thyroid hormone states can also change the epigenetic information of the male germ line, with phenotypic consequences for future generations. In the context of past literature concerning the consequences of altered thyroid hormone action for testis development, here we review recent findings about the pathophysiological roles of the principal determinants of testicular thyroid hormone action. We also discuss limited work on the effects of thyroid hormone on the male germ line epigenome and the implications for the intergenerational transmission of phenotypes via epigenetic mechanisms.

ISSN

1479-6805

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