Gene expression of leptin, leptin receptor isoforms and inflammatory cytokines in placentas of obese women – Associations to birth weight and fetal sex

• Published in: Placenta (Eastbourne) 2022-01, Vol.117, p.64-71
• Main Authors: Allbrand, Marianne, Eklund, Daniel, Cao, Yang, Nilsson, Kerstin, Lodefalk, Maria
• Format: Article
• Language: English
• Subjects: Adult; Cytokine; Cytokines - genetics; Cytokines - metabolism; Female; Gene Expression; Humans; Infant birth weight; Leptin; Leptin - genetics; Leptin - metabolism; Medicin och hälsovetenskap; Obesity; Obesity, Maternal - metabolism; Placenta; Placenta - metabolism; Pregnancy; Protein Isoforms - genetics; Protein Isoforms - metabolism; Receptor, Insulin - genetics; Receptor, Insulin - metabolism; Receptors, Leptin - genetics; Receptors, Leptin - metabolism; Young Adult
• ISSN: 0143-4004; 1532-3102; 1532-3102
• DOI: 10.1016/j.placenta.2021.10.002

Leptin signaling in placentas of obese women may influence fetal growth and may be dependent on fetal sex. The aim of this study was to investigate placental gene expression of leptin, its receptor and inflammatory cytokines in obese mothers in relation to offspring birth weight and sex. In total, 109 placental tissue samples from severely obese women (body mass index in first trimester ≥35 kg/m2) giving birth vaginally at term to a healthy child were included. Quantitative real-time PCR was used for the analysis of leptin (LEP), its receptor LEPR with two splice variants, interleukin (IL)1B, chemokine (C-X-C motif) ligand 8 (CXCL8), tumour necrosis factor (TNF), IL6, IL10, hypoxia-inducible factor 1-alpha (HIF1A) and insulin receptor (INSR). The subjects were divided into three groups based on LEP expression percentiles (75th percentile). A reverse U-shaped association between LEP expression and birth weight z-scores was found (R2 = 0.075, p = 0.005). Placental LEPRb expression was downregulated (p = 0.034) in those with highest LEP expression. Female infants had higher birth weight z-scores than males (0.58 (−1.49–2.88) vs 0.21 (−1.50–2.93), p = 0.020) and their placental LEPRb expression was upregulated (p = 0.047). The associations between expression of different genes differed by sex. A reverse U-shaped relationship between placental LEP expression and offspring birth weight z-scores was found together with sexual dimorphism in LEPRb expression indicating a complex regulation of fetal growth by placental leptin signaling in maternal obesity. •LEP expression in placentas from obese women associates with birth weight z-score.•Severely obese women with higher placental LEP expression have lower LEPRb expression.•Placental LEPRb expression is higher in females than in males born to obese mothers.•Gene expression associations in placentas from obese women differ by fetal sex.