Thyroid hormone action in the developing testis: intergenerational epigenetics

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 it 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.

Hypothyroidism: morphological and metabolic changes in the testis of adult albino rat and the amelioration by alpha-lipoic acid

“…The impact of thyroid diseases on male reproduction has been an area of controversy for many years ago, due to the reports of the inability of the testis to respond metabolically to thyroid hormones [15]. Yet, in the last decades, some clinical trials have concluded that thyroid hormones have a great role in the process of testicular spermatogenesis even at and after puberty [14]. However, some authors suggested that hypothyroidism does not influence the functions or the size of the testis or seminiferous tubules [10].…”

Protein kinase A drives paracrine crisis and WNT4-dependent testis tumor in Carney complex

“…This could play a major role in limiting SC proliferation induced by the WNT/β-catenin pathway, as suggested by previous studies on inhibin-α autocrine actions (75,76). In addition, previously defined molecular signatures attesting to SC maturation under the control of androgens (73,77,78) and thyroid hormone (79,80) remain unchanged in srKO and prKO transcriptomes at the prepubertal stage (2 weeks), but increase at adulthood. Finally, whether PKA-induced Wnt4 expression results from PKA-dependent increased Ctnnb1 expression and/or PKA-mediated β-catenin activation mechanisms, as described in ovarian granulosa and luteal cells (81)(82)(83), remains to be explored for Prkar1a -/-SCs.…”

Effect of Lighting Regimens,levels and Sources of Dietary Iodine on Semen Quality, Yolk Iodine Content and Chicks Quality Traits of Mandarah Chickens Strain

“…Also, thyroid hormones are one of factors affecting testis development 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 (Hernandez and Martinez, 2020). Moreover, Fouda et al, 2021 indicated that application of short lighting regimens,iodine,semen quality,yolk iodine content,chick quality light period (8L: 16D) can be used as alternative and beneficial strategy to rabbit producers for improving semen quality, antioxidative capacity and fertility of bucks.…”