Aging and chromatoid body assembly: Are these two physiological events linked?

Abstract

The chromatoid body is a cytoplasmic male germ cell structure that plays a role in the regulation of mRNA transcription during spermatogenesis. A proteomic analysis of this structure has identified the presence of its classic molecular markers (MVH and MIWI), as well as a significant number of transient proteins. Circadian locomotor output cycles protein kaput (CLOCK) and brain and muscle ARNT-like 1 (BMAL1), which are molecular components of the circadian clock, are likely located in the chromatoid body in a transient fashion. This study sought to determine whether aging produces morphological changes in the chromatoid bodies of round spermatids similar to those previously observed in BMAL1 knockout mice. A sample of 30 male mice was divided into three groups: juvenile mice (45 days old), adult mice (120 days old), and old mice (+180 days old). Aging was confirmed by viability and sperm count analyses and testosterone dosage. Squash slides prepared with fragments of seminiferous tubules were immunostained for MVH, MIWI, BMAL1, and CLOCK detection. In juvenile and adult specimens, single round chromatoid bodies were observed using MVH/BMAL1 and MIWI/CLOCK immunostaining. In old specimens, many chromatoid bodies displayed changes in number and morphology, as well as an increase in the interactions between MVH and BMAL1; MIWI and CLOCK. Changes in chromatoid body morphology increased interactions between the proteins analyzed herein, and decreased amounts of these proteins in seminiferous tubules of older mice may indicate that aging influences the assembly and physiology of chromatoid bodies, which may, in turn, affect fertility. Impact statement The results discussed in this paper indicate that aging compromises the structure and physiology of chromatoid bodies (CBs) in post-meiotic male cells. Since CB is a fundamental structure for the differentiation of the mature male germ cell it is possible that this imbalance in CB physiology may play a role in the reduction of fertility in older men. It is important to note that not only the classic CB markers (such as the MIWI and MVH proteins) were used to showcase the structural changes in the CBs but also the main components of circadian cycle control (the CLOCK and BMAL1 proteins), indicating that the reduction of circadian control in aged males may contribute to these changes in CBs as well. Therefore, it is intriguing to evaluate the hypothesis that controlling these physiological/structural changes in CBs may be a way of delaying the effects of aging in males.

Critical Roles of the Circadian Transcription Factor BMAL1 in Reproductive Endocrinology and Fertility

“…The chromatoid body (CB) is a special structure in pachytene spermatocytes and spermatids, which plays a pivotal role in gametogenesis during meiosis and spermatogenesis (42)(43)(44). Of interest, BMAL1 depletion converted the CB into fragments in round spermatids (18), and BMAL1 expression declined with abnormal CB structures and functions with age (45). As CB functions in mRNA silencing and translational regulation, which are important for spermatogenesis, BMAL1 might interfere with such procedures in spermatogenesis (18).…”

Refining Convergent Rate Analysis with Topology in Mammalian Longevity and Marine Transitions

“…This functional class of genes is much less studied in longevity than sets like TORC signaling and DNA repair but has intriguing ramifications and potential in the regulation of longevity. The chromatoid body is essential for maintaining male germ line quality, and its structure and function are demonstrably compromised with age ( Santos et al 2018 ). Of course, if the male germ line is compromised with age, it would be inherently difficult to select for longevity or the delayed maturation that reliably accompanies it.…”

Refining Convergent Rate Analysis with Topology in Mammalian Longevity and Marine Transitions

“…This functional class of genes is much less studied in longevity than sets like TORC signaling and DNA repair, but has intriguing ramifications and potential. The chromatoid body is essential for maintaining male germ line quality, and its structure and function is demonstrably compromised with age (Santos et al, 2018). Of course, if the male germ line is compromised with age, it would be inherently difficult to select for longevity or the delayed maturation that reliably accompanies it.…”