Transient systemic inflammation in adult male mice results in underweight progeny

Sushama Rokade, Manoj Upadhya, Dattatray S. Bhat, Nishikant Subhedar, Chittaranjan S. Yajnik, Aurnab Ghose, Satyajit Rath, Vineeta Bal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


PROBLEM: While the testes represent an immune-privileged organ, there is evidence that systemic inflammation is accompanied by local inflammatory responses. We therefore examined whether 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, twofold decrease in sperm count and reduced testicular testosterone levels were evident. When these mice were subjected to mating studies, no differences in mating efficiencies or litter sizes were observed compared with 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 methyltransferase enzyme, mixed-lineage leukaemia-1, in mice given LPS/PG/polyIC 8 weeks earlier.

CONCLUSION: Exposure to transient systemic inflammation leads to transient local inflammation in the testes, with persistent sperm-mediated consequences for foetal development.

Original languageEnglish
Article numbere13401
JournalAmerican Journal of Reproductive Immunology
Issue number1
Early online date11 Feb 2021
Publication statusPublished - Jul 2021

Bibliographical note

Funding Information:
Financial support from the DBT‐RA Program in Biotechnology and Life Sciences Department of Biotechnology, Government of India to SuR and Cognitive Science Research Initiative, Department of Science and Technology, Government of India to AG and NS (Grant No. SR/CSRI/331/2016(G)) is gratefully acknowledged. Indian Institute of Science Education and Research, Pune, is funded by Ministry of Education, Government of India.


  • epigenetics
  • inflammation
  • male fertility
  • placenta
  • progeny
  • sperm


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