RT Journal Article
SR Electronic
T1 Transient systemic inflammation in adult male mice results in underweight progeny
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.30.358697
DO 10.1101/2020.10.30.358697
A1 Rokade, Sushama
A1 Upadhya, Manoj
A1 Bhat, Dattatray S.
A1 Subhedar, Nishikant
A1 Yajnik, Chittaranjan S.
A1 Ghose, Aurnab
A1 Rath, Satyajit
A1 Bal, Vineeta
YR 2020
UL http://biorxiv.org/content/early/2020/10/30/2020.10.30.358697.abstract
AB Problem While the testes represent an immune privileged organ, there is evidence that systemic inflammation is accompanied by local inflammatory responses. We therefore examined if transient systemic inflammation caused any inflammatory and functional consequences in murine testes.Method of Study Using a single systemic administration of Toll-like receptor (TLR) agonists [lipopolysaccharide (LPS) or peptidoglycan (PG) or polyinosinic-polycytidylic acid (polyIC)] in young adult male mice, we assessed testicular immune-inflammatory landscape and reproductive functionality.Results Our findings demonstrated a significant induction of testicular TNF-α, IL-1β and IL-6 transcripts within 24 h of TLR agonist injection. By day 6 these cytokine levels returned to baseline. While there was no change in caudal sperm counts at early time points, eight weeks later, two-fold decrease of sperm count and reduced testicular testosterone levels was evident. When these mice were subjected to mating studies, no differences in mating efficiencies or litter sizes were observed compared to controls. Nonetheless, the neonatal weights of progeny from LPS/PG/polyIC treated sires were significantly lower than controls. Postnatal weight gain up to three weeks was also slower in the progeny of LPS/polyIC treated sires. Placental weights at 17.5 days post-coitum were significantly lower in females mated to LPS and polyIC treated males. Given this likelihood of an epigenetic effect, we found lower testicular levels of histone methyl-transferase enzyme, mixed-lineage leukemia-1, in mice given LPS/PG/polyIC eight weeks earlier.Conclusion Exposure to transient systemic inflammation leads to transient local inflammation in the testes, with persistent sperm-mediated consequences for fetal development.Competing Interest StatementThe authors have declared no competing interest.