Expression and clinical significance of Klotho protein in serum, umbilical cord blood, and placenta of pregnant women with intrauterine growth restriction

• Published in: Frontiers in pediatrics Vol. 13; p. 1611877
• Main Authors: Zeng, Guixiang, Lian, Jingjing, Shen, Jiajia, Shi, Yuan
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 2025
• Subjects: growth hormone; insulin-like growth factor-1; intrauterine growth restriction; Klotho; Pediatrics; placenta; intrauterine growth restriction; insulin-like growth factor-1; placenta; growth hormone; Klotho
• ISSN: 2296-2360; 2296-2360
• DOI: 10.3389/fped.2025.1611877

Intrauterine growth restriction (IUGR) significantly affects neonatal development, but its pathogenesis is not fully understood. Klotho protein is involved in aging-related diseases, and its role in fetal growth is unclear. This study aims to explore Klotho's role in IUGR. A case-control study was conducted at Nanning Maternal and Child Health Care Hospital from July 2023 to June 2024. Fifty-two neonates (gestational age ≥34 weeks and <42 weeks) were divided into the appropriate for gestational age (AGA) group (  = 30) and the IUGR group (  = 22). Venous and umbilical cord blood were collected to measure Klotho, growth hormone (GH), and insulin-like growth factor 1 (IGF-1). Placental tissues were examined for histopathology and immunohistochemistry. The IUGR group showed placental morphological changes, including increased syncytial knots and inflammation. Klotho expression in placental tissue was significantly reduced (  < 0.0001), while IGF-1 levels increased (  < 0.001) and GH levels decreased (  < 0.001). Soluble α-Klotho levels were lower in maternal venous blood (  < 0.0001) and umbilical cord blood (  < 0.01). GH and IGF-1 levels in maternal venous blood and umbilical cord blood were altered in IUGR cases. Reduced Klotho expression in IUGR cases, along with changes in GH and IGF-1, suggests disruptions in metabolic processes affecting fetal growth and development. These findings suggest a potential involvement of Klotho in placental changes and fetal development, warranting further mechanistic studies.