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Updated: Sep 17, 2026

Generating a Reproducible Model of Mid-Gestational Maternal Immune Activation using Poly(I:C) to Study Susceptibility and Resilience in Offspring
Published on: August 17, 2022
Repeated low-dose lipopolysaccharide exposure during the periconception period on ewe immune responses and lamb
J F Dominguez Arellanes1, K L Luna1, S C Gurule1
1Department of Animal and Range Sciences, New Mexico State University, Las Cruces, NM 88003, United States.
Abstract:
Subclinical inflammatory challenges caused by gram-negative bacterial endotoxin lipopolysaccharide (LPS) may disrupt reproductive physiology and influence offspring development; however, the effects of repeated low-dose exposure during the periconception period remain unclear. Therefore, this study evaluated the effects of repeated low-dose LPS exposure on maternal immune and endocrine responses, reproductive performance, and offspring growth and development. Rambouillet ewes (n = 30; 2 to 8 yr; 61 ± 6 kg BW) were stratified by body weight and age and assigned to receive subcutaneous injections of saline (CON; n = 10), 1.5 µg/kg BW LPS (LOW; n = 10), or 3.0 µg/kg BW LPS (HIGH; n = 10) on d 5, 10, and 15 of a synchronized estrous cycle prior to breeding. Rectal temperature, serum cortisol, and complete blood count (CBC) parameters were measured before and after LPS administration, with repeated measurements collected through 24 h following treatment. Reproductive performance was evaluated after a 35-d breeding season, and lamb hematology, growth, morphometric traits, and wool characteristics were assessed from birth through weaning (d 60) and repeated-measures outcomes were analyzed using mixed-effects models. Maternal LPS exposure increased rectal temperature and serum cortisol on day 5 (treatment × hour, P ≤ 0.05). Cortisol responses remained elevated across repeated exposures (treatment × hour, P ≤ 0.05), but rectal temperatures did not differ on subsequent LPS challenge days. Total white blood cell, and lymphocyte concentrations decreased 2 to 4 h after treatment and increased at 24 h on d 5 (treatment × hour, P ≤ 0.05). Red blood cell and platelet parameters were minimally affected by treatment. Maternal LPS exposure did not affect conception rate, pregnancy rate, or lamb production traits. However, offspring from LOW-treated ewes had greater total white blood cell, lymphocyte, and neutrophil concentrations at birth and increased neutrophil concentrations at d 14 (P ≤ 0.05), but these differences were not maintained through weaning. No treatment effects were detected for lamb growth, morphometric development, or wool characteristics. Collectively, these results indicate that repeated low-dose maternal LPS exposure during the periconception period alters maternal immune responses and is associated with transient alterations in neonatal white blood cell profiles without affecting reproductive performance or growth outcomes.
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