Abstract
The placental hormone leptin has important functions in fetal and neonatal growth, and prevents depressed respiration in leptin-deficient mice. The effect of leptin on respiratory distress suffered by low birth weight and premature infants has been studied. However, it is unclear how leptin enhances lung maturity in the fetus and ameliorates neonatal respiratory distress. In the present study, we found that antenatal treatment with leptin for 2 d significantly enhanced the relative alveolus area and improved the maturity of fetal lungs in a rat model of fetal growth restriction (FGR). Mean birth weight and lung wet weight were higher in the leptin-treated group than in the PBS-treated group, indicating promotion of fetal growth. Leptin upregulated the intracellular expression and extracellular secretion of surfactant protein (SP) A in type-II alveolar epithelial cells (AECs) in vivo and in vitro. Dual positive effects of leptin were found on protein expression and transcriptional activity of thyroid transcription factor-1 (TTF-1), a nuclear transcription essential for branching morphogenesis of the lung and expression of SP-A in type-II AECs. Knockdown of TTF-1 by RNA interference indicated that TTF-1 may play a vital role in leptin-induced SP-A expression. These results suggest that leptin may have great therapeutic potential for the treatment of FGR, and leptin-mediated SP-A induction and lung maturity of the fetus are TTF-1 dependent.
Highlights
Fetal growth restriction (FGR), known as fetal intrauterine growth retardation, refers to a condition in which a fetus has failed to achieve its genetically determined growth potential and affects up to 5–10% of pregnancies [1]
We found that the leptin/Lep-R system was expressed in the fetal lungs and was detected at lower levels in the FGR group than in the sham control group
We investigated in FGR rats whether leptin modulates the expression of major surfactant proteins, which is the definitive characteristic of type-II alveolar epithelial cells (AECs)
Summary
Fetal growth restriction (FGR), known as fetal intrauterine growth retardation, refers to a condition in which a fetus has failed to achieve its genetically determined growth potential and affects up to 5–10% of pregnancies [1]. Studies have suggested that several cytokines and their receptors are localized in developing pulmonary tissues, and they play major roles in pulmonary epithelial cell differentiation and lung maturity [7,8,9,10,11]. These cytokines and receptors have great therapeutic potential for the treatment of FGR. Some studies have indicated that a lack of exposure to leptin late in pregnancy, when type-II AECs are maturing and producing surfactant, could contribute to the respiratory distress that occurs in FGR infants [8,11]. Leptin may be an important regulator of pulmonary epithelial differentiation and lung development in the fetus [8,10,11,17,22]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
