Thymus development in the zebrafish (Danio rerio) from an ecoimmunology perspective

Abstract

The thymus is present in all gnathostome vertebrates and is an essential organ for the adaptive immune system via the generation of functional mature T‐cells. Over the life span of mammals, the thymus undergoes morphological and functional alterations, including an age‐related involution, which in humans starts in early life. Life history tradeoffs have been suggested as possible reasons for thymus involution. While in teleost fish, only a few studies have investigated alterations of thymus structure and function over different life stages, resulting in a fragmented database. Here, we investigated the thymus growth of zebrafish (Danio rerio) from early life, throughout puberty and reproductive stage, up to 1‐year‐old. We assessed thymus growth by histological and morphometric analyses and thymocyte numbers. Thymus function was assessed by measuring the transcripts of the thymocyte marker genes, ikaros, tcrα, and tcrδ. Additionally, we analyzed gonad maturity and tail homogenate vitellogenin concentrations to align thymus status with the status of the reproductive system. Our results showed that the zebrafish thymus, in contrast to the human thymus, grew strongly during early life and puberty but started to undergo involution when the fish reached the reproductive age. The involution was characterized by reduced thymus area and thymocyte number, altered histoarchitecture, and decreasing thymocyte marker gene transcript levels. Our findings suggest that age‐related changes of the zebrafish thymus do exist and could be partly explained in terms of resource tradeoffs, but also in terms of the ontogenetically late development of a functional adaptive immune system in teleosts.

Prepubertal gonad investment modulates thymus function: evidence in a teleost fish

“…This study, therefore, provides experimental evidence that helps to explain the physiological relevance of the evolutionarily conserved thymus atrophy in view of limited resources and energy trade-offs between immunity, growth and reproduction. Hence, it confirms the hypothesis of a link between energetic costs, sex steroid hormones and thymus atrophy (Aw and Palmer, 2012;Chaudhry et al, 2016;Cockburn, 1992;Kernen et al, 2020). This finding has importance beyond fish.…”

“…Consequently, this study shows that thymus atrophy in female sea bass occurs with the first gonadal development during proliferation of primary oocytes in prepuberty (Papadaki et al, 2005). In contrast, in female zebrafish, thymus atrophy occurs in puberty with no apparent reduction of thymus growth in prepuberty (Kernen et al, 2020). In medaka, the thymus growth is apparently reduced by puberty and the rise of sex hormones.…”

Exploiting the Differences Between Zebrafish and Medaka in Biological Research: A Complementary Approach

“…Furthermore, optical transparency which is seen as a critical advantage of using zebrafish and medaka for research involving the tracking of molecules and lymphoid progenitors from hematopoietic tissue is premised on the closeness of the thymus to the skin [27]. Zebrafish larvae have between 20 and 50 thymocytes, while freshly hatched medaka have more than 1000 thymocytes [29].…”