Oxidative stress has been implicated in an extensive range of age-related pathologies and is a well-known cause of infertility. The negative impacts of oxidative stress on male and female germ cell viability are primarily underpinned by the peroxidation of fatty acids, resulting in the production of highly reactive lipid aldehydes, such as 4-hydroxynonenal (4HNE). In many cell types, the portion of the cell proteome that is targeted for 4HNE-modification often experiences severe protein misfolding that, in turn, leads to a disruption of protein homeostasis (proteostasis). This study was designed to explore a relationship between oxidative stress, ageing and protein aggregation in male and female germ cells with a key focus on uncovering mechanisms to prevent protein damage. Through the development of several robust strategies for the detection of protein aggregates, this study has revealed a causative role for oxidative stress in the induction of protein aggregation in both pachytene spermatocytes and round spermatids. Specifically, the exogenous application of 0.1mM 4HNE to these cells resulted in a significant increase in aggregation (P<0.005) detectable with the amyloid-specific fluorophores Proteostat and Thioflavin T, and the conformer specific antibodies anti-A11 and anti-OC. In this study, nucleocytoplasmic transport was examined as a potential mechanism for the subcellular compartmentalisation of aggregating proteins. The inhibition of transport proteins karyopherin beta 1/alpha 2 (KPNB1/A2) and exportin 1 (XPO1), resulted in a significant increase in cellular protein aggregates in male germ cells (P<0.005). In the female germline, both in vivo and in vitro oocyte ageing resulted in the development of cytoplasmic protein aggregates in germinal vesicle oocytes, with the subcellular compartmentalisation of these aggregates tightly control by XPO1. These results reveal the importance of functional nucleocytoplasmic transport systems for the management of misfolded proteins in male and female germ cells.