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

Pediatric Research volume 95, pages 1503–1509 (2024)Cite this article

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 Blood was withdrawn from the heart to determine leptin levels.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.

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Fig. 1: The effect of UPI on rat pup weight and serum leptin.
Fig. 2: The effect of UPI on lung leptin and leptin-receptor expression.
Fig. 3: The effect of UPI on lung morphometry.
Fig. 4: The effect of UPI on lung PCNA expression.
Fig. 5: Strong correlation between serum leptin, RAC, and vWF.

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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank Zheng-Hao Huang for the technical assistance.

Funding

This work was supported by a grant from the Ministry of Science and Technology of Taiwan (MOST 111-2314-B-038-113-MY2).

Author information

Authors and Affiliations

  1. International PhD Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Merryl Esther Yuliana & Chung-Ming Chen

  2. Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Hsiu-Chu Chou

  3. Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

    Emily Chia-Yu Su

  4. Research Center for Artificial Intelligence in Medicine, Taipei Medical University, Taipei, Taiwan

    Emily Chia-Yu Su

  5. School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Hsiao-Chi Chuang

  6. Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Hsiao-Chi Chuang

  7. Department of Pediatrics, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

    Liang-Ti Huang

  8. Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Liang-Ti Huang & Chung-Ming Chen

  9. Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan

    Chung-Ming Chen

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  1. Merryl Esther Yuliana
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Contributions

The experiments were conducted at the animal center of Taipei Medical University. C-MC. contributed to the conception and design of this study. M.Y., H.-C.C., E. C.-YS., H.-C.C., L.-T.H. and C.-M.C contributed to the performance of the experiments, analysis and interpretation of the data, and approval of the manuscript. All authors agree to assume responsibility for all aspects of the work to ensure proper investigation and resolution of issues related to the accuracy or integrity of any part of the work. All authors contributed to the article and approved the submitted version.

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Correspondence to Chung-Ming Chen.

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Yuliana, M.E., Chou, HC., Su, E.CY. et al. Uteroplacental insufficiency decreases leptin expression and impairs lung development in growth-restricted newborn rats. Pediatr Res 95, 1503–1509 (2024). https://doi.org/10.1038/s41390-023-02946-y

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