Section of Neonatology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
Sci Rep. 2019 Jun 11;9(1):8514. doi: 10.1038/s41598-019-44955-0.
Being of the male sex has been identified as a risk factor for multiple morbidities associated with preterm birth, including bronchopulmonary dysplasia (BPD). Exposure to inflammatory stress is a well-recognized risk factor for developing BPD. Whether there is a sex difference in pulmonary innate immune TLR4 signaling, lung injury and subsequent abnormal lung development is unknown. Neonatal (P0) male and female mice (ICR) were exposed to systemic LPS (5 mg/kg, IP) and innate immune signaling, and the transcriptional response were assessed (1 and 5 hours), along with lung development (P7). Male and female mice demonstrated a similar degree of impaired lung development with decreased radial alveolar counts, increased surface area, increased airspace area and increased mean linear intercept. We found no differences between male and female mice in the baseline pulmonary expression of key components of TLR4-NFκB signaling, or in the LPS-induced pulmonary expression of key mediators of neonatal lung injury. Finally, we found no difference in the kinetics of LPS-induced pulmonary NFκB activation between male and female mice. Together, these data support the conclusion that the innate immune response to early postnatal LPS exposure and resulting pulmonary sequelae is similar in male and female mice.
男性性别已被确定为与早产相关的多种疾病的危险因素之一，包括支气管肺发育不良（BPD）。暴露于炎症应激是发生 BPD 的一个公认危险因素。肺部先天免疫 TLR4 信号、肺损伤和随后的异常肺发育是否存在性别差异尚不清楚。新生（P0）雄性和雌性小鼠（ICR）接受全身 LPS（5mg/kg，IP）暴露和先天免疫信号转导，并评估转录反应（1 和 5 小时），以及肺发育（P7）。雄性和雌性小鼠的肺发育受损程度相似，表现为肺泡计数减少、表面积增加、气腔面积增加和平均线性截距增加。我们没有发现雄性和雌性小鼠在 TLR4-NFκB 信号的关键组成部分的基础肺表达或新生儿肺损伤的关键介质的 LPS 诱导的肺表达之间存在差异。最后，我们没有发现 LPS 诱导的肺 NFκB 激活在雄性和雌性小鼠之间的动力学存在差异。总之，这些数据支持以下结论：对新生后 LPS 暴露的先天免疫反应以及由此产生的肺部后遗症在雄性和雌性小鼠中相似。
