Disruption of the SP-A/SP-R210L (Myo18Aα) pathway prolongs gestation and reduces fetal survival during lipopolysaccharide-induced parturition in late gestation

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Am J Physiol Lung Cell Mol Physiol. 2024 Feb 13. doi: 10.1152/ajplung.00383.2023.

Disruption of the SP-A/SP-R210L (Myo18Aα) pathway prolongs gestation and reduces fetal survival during lipopolysaccharide-induced parturition in late gestation

Zhiwei Guan, Brandon Worth, Todd M Umstead, Shaili Amatya, Jennifer Booth, Zissis C Chroneos

Pediatrics, Penn State Milton S. Hershey Medical Center, Hershey, PA, United States. Pediatrics, Pennsylvania State University, Hershey, PA, United States.

Service type: Knockout mice


Prolonged labor can lead to infection, fetal distress, asphyxia, and life-threatening harm to both the mother and baby. Surfactant Protein A (SP-A) was shown to contribute to maintenance of pregnancy and timing of term labor. SP-A modulates the stoichiometric expression of the SP-R210L and SP-R210S isoforms of the SP-R210 receptor on alveolar macrophages (AMs). Lack of SP-R210L dysregulates macrophage inflammatory responses. We asked whether SP-A alters normal and inflammation-induced parturition through SP-R210 using SP-A- and SP-R210L-deficient mice. Labor and delivery of time-pregnant mice were monitored in real-time using a time-lapse infrared camera. Intrauterine injection with either vehicle or Escherichia coli lipopolysaccharide (LPS) on embryonic (E) day 18.5 post-coitus was used to assess the effect of gene disruption in chorioamnionitis-induced labor. We report that either lack of SP-A or disruption of SP-R210L delays parturition by 0.40 and 0.55 days compared to controls, respectively. LPS induced labor 0.60, 1.01, 0.40, 1.00, and 1.31 days earlier than PBS controls in WT, SP-A-deficient, littermate controls, heterozygous, and homozygous SP-R210L-deficient mice, respectively. Lack of SP-A reduced litter size in PBS-treated mice, whereas the total number of pups delivered was similar in all LPS-treated mice. The number of live pups, however, was significantly reduced by 50-70% in SP-A and SP-R210L-deficient mice compared to controls. Differences in gestational length were not associated with intrauterine growth restriction. The present findings support the novel concept that the SP-A/SP-R210 pathway modulates timely labor and delivery and supports fetal lung barrier integrity during fetal to neonatal transition in term pregnancy.

Keywords: Chorioamnionitis; Inflammation; Parturition; SP-A receptor 210 (SP-R210); Surfactant Protein A (SP-A).

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