Uteroplacental insufficiency decreases leptin expression and impairs lung development in growth-restricted newborn rats

Merryl Esther Yuliana; Hsiu-Chu Chou; Emily Chia-Yu Su; Hsiao-Chi Chuang; Liang-Ti Huang; Chung-Ming Chen

doi:10.1038/s41390-023-02946-y

Uteroplacental insufficiency decreases leptin expression and impairs lung development in growth-restricted newborn rats

Pediatr Res. 2023 Dec 5. doi: 10.1038/s41390-023-02946-y. Online ahead of print.

Authors

Merryl Esther Yuliana¹, Hsiu-Chu Chou², Emily Chia-Yu Su^{3

4}, Hsiao-Chi Chuang^{5

6}, Liang-Ti Huang^{7

8}, Chung-Ming Chen^{9

10

11}

Affiliations

¹ International PhD Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
² Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
³ Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
⁴ Research Center for Artificial Intelligence in Medicine, Taipei Medical University, Taipei, Taiwan.
⁵ School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁶ Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁷ Department of Pediatrics, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
⁸ Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁹ International PhD Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. cmchen@tmu.edu.tw.
¹⁰ Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. cmchen@tmu.edu.tw.
¹¹ Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan. cmchen@tmu.edu.tw.

PMID: 38049649
DOI: 10.1038/s41390-023-02946-y

Abstract

Background: The study aimed to analyze the effect of uteroplacental insufficiency (UPI) on leptin expression and lung development of intrauterine growth restriction (IUGR) rats.

Methods: On day 17 of pregnancy, time-dated Sprague-Dawley rats were randomly divided into either an IUGR group or a control group. Uteroplacental insufficiency surgery (IUGR) and sham surgery (control) were conducted. Offspring rats were spontaneously delivered on day 22 of pregnancy. On postnatal days 0 and 7, rats' pups were selected at random from the control and IUGR groups. Blood was withdrawn from the heart to determine leptin levels. The right lung was obtained for leptin and leptin receptor levels, immunohistochemistry, proliferating cell nuclear antigen (PCNA), western blot, and metabolomic analyses.

Results: UPI-induced IUGR decreased leptin expression and impaired lung development, causing decreased surface area and volume in offspring. This results in lower body weight, decreased serum leptin levels, lung leptin and leptin receptor levels, alveolar space, PCNA, and increased alveolar wall volume fraction in IUGR offspring rats. The IUGR group found significant relationships between serum leptin, radial alveolar count, von Willebrand Factor, and metabolites.

Conclusion: Leptin may contribute to UPI-induced lung development during the postnatal period, suggesting supplementation as a potential treatment.

Impact: The neonatal rats with intrauterine growth restriction (IUGR) caused by uteroplacental insufficiency (UPI) showed decreased leptin expression and impaired lung development. UPI-induced IUGR significantly decreased surface area and volume in lung offspring. This is a novel study that investigates leptin expression and lung development in neonatal rats with IUGR caused by UPI. If our findings translate to IUGR infants, leptin may contribute to UPI-induced lung development during the postnatal period, suggesting supplementation as a potential treatment.