Decreased Expression of Placental Proteins in Recurrent Pregnancy Loss: Functional Relevance and Diagnostic Value

• Published in: International journal of molecular sciences 2024-02, Vol.25 (3), p.1865
• Main Authors: Tóth, Eszter, Györffy, Dániel, Posta, Máté, Hupuczi, Petronella, Balogh, Andrea, Szalai, Gábor, Orosz, Gergő, Orosz, László, Szilágyi, András, Oravecz, Orsolya, Veress, Lajos, Nagy, Sándor, Török, Olga, Murthi, Padma, Erez, Offer, Papp, Zoltán, Ács, Nándor, Than, Nándor Gábor
• Format: Article
• Language: English
• Subjects: Biomarkers; Blood proteins; Chorionic gonadotropin; Gestational age; Glycoproteins; Miscarriage; Pregnancy; Proteins; Reproductive health; Scientific equipment and supplies industry
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25031865

Miscarriages affect 50-70% of all conceptions and 15-20% of clinically recognized pregnancies. Recurrent pregnancy loss (RPL, ≥2 miscarriages) affects 1-5% of recognized pregnancies. Nevertheless, our knowledge about the etiologies and pathophysiology of RPL is incomplete, and thus, reliable diagnostic/preventive tools are not yet available. Here, we aimed to define the diagnostic value of three placental proteins for RPL: human chorionic gonadotropin free beta-subunit (free-β-hCG), pregnancy-associated plasma protein-A (PAPP-A), and placental growth factor (PlGF). Blood samples were collected from women with RPL ( = 14) and controls undergoing elective termination of pregnancy ( = 30) at the time of surgery. Maternal serum protein concentrations were measured by BRAHMS KRYPTOR Analyzer. Daily multiple of median (dMoM) values were calculated for gestational age-specific normalization. To obtain classifiers, logistic regression analysis was performed, and ROC curves were calculated. There were differences in changes of maternal serum protein concentrations with advancing healthy gestation. Between 6 and 13 weeks, women with RPL had lower concentrations and dMoMs of free β-hCG, PAPP-A, and PlGF than controls. PAPP-A dMoM had the best discriminative properties (AUC = 0.880). Between 9 and 13 weeks, discriminative properties of all protein dMoMs were excellent (free β-hCG: AUC = 0.975; PAPP-A: AUC = 0.998; PlGF: AUC = 0.924). In conclusion, free-β-hCG and PAPP-A are valuable biomarkers for RPL, especially between 9 and 13 weeks. Their decreased concentrations indicate the deterioration of placental functions, while lower PlGF levels indicate problems with placental angiogenesis after 9 weeks.