Abstract
Paternal experiences and exposures prior to conception can influence fetal development and offspring phenotype. The composition of seminal plasma contributes to paternal programming effects, through modulating the female reproductive tract immune response after mating. To investigate whether paternal obesity affects seminal plasma immune-regulatory activity, C57Bl/6 male mice were fed an obesogenic high fat diet (HFD) or control diet (CD) for 14 weeks. While HFD consumption caused only minor changes to parameters of sperm quality, the volume of seminal vesicle fluid secretions was increased by 65%, and the concentrations and total content of immune-regulatory TGFB isoforms were decreased by 75-80% and 43-55% respectively. Mating with BALB/c females revealed differences in the strength and properties of the post-mating immune response elicited. Transcriptional analysis showed >300 inflammatory genes were similarly regulated in the uterine endometrium by mating independently of paternal diet, but 13 were dysregulated by HFD-fed compared to CD-fed males. Seminal vesicle fluid factors reduced in HFD-fed males, including TGFB1, IL10, and TNF, were amongst the predicted upstream regulators of differentially regulated genes. Additionally, the T cell response induced by mating with CD-fed males was blunted after mating with HFD-fed males, with 27% fewer CD4 + T cells, 26% fewer FOXP3 +CD4 + regulatory T cells (Treg) cells, and 19% fewer CTLA4 + Treg cells, particularly within the NRP1 + thymic Treg cell population. These findings demonstrate that an obesogenic high fat diet alters the composition of seminal vesicle fluid and impairs seminal plasma capacity to elicit a favorable pro-tolerogenic immune response in females at conception.
Analysis of bull (Bos taurus) seminal vesicle fluid proteome in relation to seminal plasma proteome
