Proteomic Dissection of the Impact of Environmental Exposures on Mouse Seminal Vesicle Function

Seminal vesicles are an integral part of the male reproductive accessory gland system. They produce a complex array of secretions containing bioactive constituents that support gamete function and promote reproductive success, with emerging evidence suggesting these secretions are influenced by our environment. Despite their significance, the biology of seminal vesicles remains poorly defined. Here, we complete the first proteomic assessment of mouse seminal vesicles and assess the impact of the reproductive toxicant acrylamide. Mice were administered acrylamide (25 mg/kg bw/day) or control daily for five consecutive days prior to collecting seminal vesicle tissue. A total of 5013 proteins were identified in the seminal vesicle proteome with bioinformatic analyses identifying cell proliferation, protein synthesis, cellular death, and survival pathways as prominent biological processes. Secreted proteins were among the most abundant, and several proteins are linked with seminal vesicle phenotypes. Analysis of the effect of acrylamide on the seminal vesicle proteome revealed 311 differentially regulated (FC ± 1.5, p ≤ 0.05, 205 up-regulated, 106 downregulated) proteins, orthogonally validated via immunoblotting and immunohistochemistry. Pathways that initiate protein synthesis to promote cellular survival were prominent among the dysregulated pathways, and rapamycin-insensitive companion of mTOR (RICTOR, p = 6.69E-07) was a top-ranked upstream driver. Oxidative stress was implicated as contributing to protein changes, with acrylamide causing an increase in 8-OHdG in seminal vesicle epithelial cells (fivefold increase, p = 0.016) and the surrounding smooth muscle layer (twofold increase, p = 0.043). Additionally, acrylamide treatment caused a reduction in seminal vesicle secretion weight (36% reduction, p = 0.009) and total protein content (25% reduction, p = 0.017). Together these findings support the interpretation that toxicant exposure influences male accessory gland physiology and highlights the need to consider the response of all male reproductive tract tissues when interpreting the impact of environmental stressors on male reproductive function.
Graphical abstract
Highlights • First proteomic characterization of the mouse seminal vesicle tissue. • Secreted proteins are among the most abundant proteins in the seminal vesicle tissue. • Paternal exposure to reproductive toxicant acrylamide alters seminal vesicle proteome. • Acrylamide treatment results in reduced seminal vesicle secretory capacity.
In Brief Seminal vesicles produce bioactive constituents that support gamete function and promote reproductive success. Despite their significance, seminal vesicle biology remains poorly defined. Here, we have exploited proteomics to generate the first mechanistic insights into mouse seminal vesicles in normal physiology and pathology. Our collective data affirm the hypothesis that seminal vesicles are sensitive to environmental factors and exposures in a manner that may have consequences for fetal development and later offspring health.