Aging and sperm signals alter DNA break formation and repair in the C. elegans germline

Abstract

Female reproductive aging is associated with decreased oocyte quality and fertility. The nematode Caenorhabditis elegans is a powerful system for understanding the biology of aging and exhibits age-related reproductive defects that are analogous to those observed in many mammals, including dysregulation of DNA repair. C. elegans germline function is influenced simultaneously by both reproductive aging and signals triggered by limited supplies of sperm, which are depleted over chronological time. To delineate the causes of DNA repair defects in aged C. elegans germlines, we assessed both DNA double strand break (DSB) induction and repair during meiotic prophase I progression in aged germlines which were depleted of self-sperm, mated, or never exposed to sperm. We find that germline DSB induction is dramatically reduced only in hermaphrodites which have exhausted their endogenous sperm, suggesting that a signal due specifically to sperm depletion downregulates DSB formation. We also find that DSB repair is delayed in aged germlines regardless of whether hermaphrodites had either a reduction in sperm supply or an inability to endogenously produce sperm. These results demonstrate that in contrast to DSB induction, DSB repair defects are a feature of C. elegans reproductive aging independent of sperm presence. Finally, we demonstrate that the E2 ubiquitin-conjugating enzyme variant UEV-2 is required for efficient DSB repair specifically in young germlines, implicating UEV-2 in the regulation of DNA repair during reproductive aging. In summary, our study demonstrates that DNA repair defects are a feature of C. elegans reproductive aging and uncovers parallel mechanisms regulating efficient DSB formation in the germline.

Chromosomal aberrations and early mortality in a non-mammalian vertebrate: example from triploid-induced Atlantic salmon

“…The association between chromosomal aberrations and spontaneous abortions and pathologies have also been observed in domesticated mammals like equines (Shilton et al, 2020), bovines (Schmutz et al, 1996), and in mouse models (Williams et al, 2008). Studies on humans (Taylor et al, 2014;Thomas et al, 2021;Webster & Schuh, 2017), other mammals (Rizzo et al, 2019), and even the model nematode Caenorhabditis elegans (Toraason et al, 2022) have demonstrated that variables relating to the maternal germline, and in particular oocyte age, may increase the probability of nondisjunction during meiosis. The current evidence, while mostly limited to humans and domesticated mammals, suggests that chromosomal aberrations and their impacts on tness may be prevalent across taxa, and may be predisposed by genetic and environmental factors.…”