Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

Leptin deficiency, a potential mechanism for impaired fetal lung development in uteroplacental insufficiency?

Pediatric Research (2024)Cite this article

Abstract

Uteroplacental insufficiency (UPI) is a major cause of fetal growth restriction (FGR). Leptin, an adipokine, has been shown to play a vital role in fetal organogenesis. There is evidence reporting leptin deficiency in preterm and growth-restricted fetuses. In this issue of Pediatric Research, Yuliana et al. report leptin expression and lung development in UPI-induced FGR rats. UPI-induced FGR rats expressed decreased lung leptin and had impaired lung development, as shown by decreased surface area and lung volume. They also found a significant association between lung radial alveolar count, serum leptin, von Willebrand factor, and specific metabolites on metabolomic analyses. Previous studies on leptin supplementation in vivo have been associated with improvement in lung maturation; supporting the evidence, that leptin improves lung growth and development in FGR and may have future therapeutic potential in the improvement of respiratory outcomes in these infants. Future studies to support evidence of this association in humans are warranted.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Sun, L. The update of fetal growth restriction associated with biomarkers. Matern. Fetal Med. 4, 210–217 (2022).

    Article  Google Scholar 

  2. Burton, G. J. & Jauniaux, E. Pathophysiology of placental-derived fetal growth restriction. Am. J. Obstet. Gynecol. 218, S745–S761 (2018).

    Article  CAS  PubMed  Google Scholar 

  3. Sehgal, A., Dassios, T., Nold, M. F., Nold-Petry, C. A. & Greenough, A. Fetal growth restriction and neonatal-pediatric lung diseases: Vascular mechanistic links and therapeutic directions. Paediatr. Respir. Rev. 44,19–30 (2022).

  4. Yuliana, M. E., Huang, Z. H., Chou, H. C. & Chen, C. M. Effects of uteroplacental insufficiency on growth-restricted rats with altered lung development: a metabolomic analysis. Front. Pediatr. 10, 952313 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Valenzuela, I. et al. Long-term pulmonary and neurodevelopmental impairment in a fetal growth restriction rabbit model. Sci. Rep. 13, 20966 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Malhotra, A. et al. Neonatal morbidities of fetal growth restriction: pathophysiology and impact. Front. Endocrinol. 10, 55 (2019).

    Article  Google Scholar 

  7. Huang, L. T., Chou, H. C., Lin, C. M. & Chen, C. M. Uteroplacental insufficiency alters the retinoid pathway and lung development in newborn rats. Pediatr. Neonatol. 57, 508–514 (2016).

    Article  PubMed  Google Scholar 

  8. Yang, Y. C., Chou, H. C., Liu, Y. R. & Chen, C. M. Uteroplacental insufficiency causes microbiota disruption and lung development impairment in growth-restricted newborn rats. Nutrients 14, 4388 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Arigliani, M. et al. Lung function between 8 and 15 years of age in very preterm infants with fetal growth restriction. Pediatr. Res. 90, 657–663 (2021).

    Article  PubMed  Google Scholar 

  10. Joss-Moore, L. et al. Intrauterine growth restriction transiently delays alveolar formation and disrupts retinoic acid receptor expression in the lung of female rat pups. Pediatr. Res. 73, 612–620 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chen, H. et al. Leptin promotes fetal lung maturity and upregulates SP-A expression in pulmonary alveoli type-II epithelial cells involving TTF-1 activation. PLoS ONE 8, e69297 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cetin, I. et al. Fetal plasma leptin concentrations: relationship with different intrauterine growth patterns from 19 weeks to term. Pediatr. Res. 48, 646–651 (2000).

    Article  CAS  PubMed  Google Scholar 

  13. Steinbrekera, B. et al. Origins of neonatal leptin deficiency in preterm infants. Pediatr. Res. 85, 1016–1023 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Nüsken, E. et al. Reduced perinatal leptin availability may contribute to adverse metabolic programming in a rat model of uteroplacental insufficiency. Endocrinology 157, 1813–1825 (2016).

    Article  PubMed  Google Scholar 

  15. Kirwin, S. M. et al. Leptin enhances lung maturity in the fetal rat. Pediatr. Res. 60, 200–204 (2006).

    Article  CAS  PubMed  Google Scholar 

  16. Malli, F., Papaioannou, A. I., Gourgoulianis, K. I. & Daniil, Z. The role of leptin in the respiratory system: an overview. Respir. Res. 11, 1–6 (2010).

    Article  Google Scholar 

  17. De Blasio, M. J. et al. Leptin matures aspects of lung structure and function in the ovine fetus. Endocrinology 157, 395–404 (2016).

    Article  PubMed  Google Scholar 

  18. Huang, K. et al. Effects of leptin deficiency on postnatal lung development in mice. J. Appl. Physiol. 105, 249–259 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Gnanalingham, M. G., Mostyn, A., Gardner, D. S., Stephenson, T. & Symonds, M. E. Developmental regulation of the lung in preparation for life after birth: hormonal and nutritional manipulation of local glucocorticoid action and uncoupling protein–2. J. Endocrinol. 188, 375–386 (2006).

    Article  CAS  PubMed  Google Scholar 

  20. de Knegt, V. E. et al. The role of leptin in fetal growth during pre-eclampsia. Int. J. Mol. Sci. 22, 4569 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Attig, L., Larcher, T., Gertler, A., Abdennebi-Najar, L. & Djiane, J. Postnatal leptin is necessary for maturation of numerous organs in newborn rats. Organogenesis 7, 88–94 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Ip, B. C. et al. Does fetal leptin and adiponectin influence children’s lung function and risk of wheeze? J. Dev. Orig. Health Dis. 12, 570–577 (2021).

    Article  CAS  PubMed  Google Scholar 

  23. Briffa, J. F., McAinch, A. J., Romano, T., Wlodek, M. E. & Hryciw, D. H. Leptin in pregnancy and development: a contributor to adulthood disease? Am. J. Physiol.-Endocrinol. Metab. 308, E335–E350 (2015).

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Dr. Mohan Pammi is funded by the following extramural source: NIH 1R01HD112886.

Author information

Authors and Affiliations

  1. Dept. of Pediatrics, Division of Neonatology, Baylor College of Medicine & Texas Children’s Hospital, Houston, TX, USA

    Srirupa Hari Gopal & Mohan Pammi

  2. Dept. of Obstetrics & Gynecology, Maternal-Fetal Medicine, Baylor College of Medicine & Texas Children’s Hospital, Houston, TX, USA

    Roopali Donepudi

Authors
  1. Srirupa Hari Gopal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roopali Donepudi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohan Pammi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohan Pammi.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gopal, S.H., Donepudi, R. & Pammi, M. Leptin deficiency, a potential mechanism for impaired fetal lung development in uteroplacental insufficiency?. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03038-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41390-024-03038-1

Search

Advanced search

Quick links