Decreased Expression of Placental Proteins in Recurrent Pregnancy Loss: Functional Relevance and Diagnostic Value
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 diagnos...
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MDPI AG
2024-02-01
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| author | Eszter Tóth Dániel Györffy Máté Posta Petronella Hupuczi Andrea Balogh Gábor Szalai Gergő Orosz László Orosz András Szilágyi Orsolya Oravecz Lajos Veress Sándor Nagy Olga Török Padma Murthi Offer Erez Zoltán Papp Nándor Ács Nándor Gábor Than |
| author_facet | Eszter Tóth Dániel Györffy Máté Posta Petronella Hupuczi Andrea Balogh Gábor Szalai Gergő Orosz László Orosz András Szilágyi Orsolya Oravecz Lajos Veress Sándor Nagy Olga Török Padma Murthi Offer Erez Zoltán Papp Nándor Ács Nándor Gábor Than |
| author_sort | Eszter Tóth |
| collection | DOAJ |
| description | 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 (<i>n</i> = 14) and controls undergoing elective termination of pregnancy (<i>n</i> = 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. |
| first_indexed | 2024-03-08T03:55:08Z |
| format | Article |
| id | doaj.art-ebd255c6287041f6812632da19299957 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T03:55:08Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ebd255c6287041f6812632da192999572024-02-09T15:14:55ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-02-01253186510.3390/ijms25031865Decreased Expression of Placental Proteins in Recurrent Pregnancy Loss: Functional Relevance and Diagnostic ValueEszter Tóth0Dániel Györffy1Máté Posta2Petronella Hupuczi3Andrea Balogh4Gábor Szalai5Gergő Orosz6László Orosz7András Szilágyi8Orsolya Oravecz9Lajos Veress10Sándor Nagy11Olga Török12Padma Murthi13Offer Erez14Zoltán Papp15Nándor Ács16Nándor Gábor Than17Systems Biology of Reproduction Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Magyar Tudósok Körútja 2, H-1117 Budapest, HungarySystems Biology of Reproduction Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Magyar Tudósok Körútja 2, H-1117 Budapest, HungarySystems Biology of Reproduction Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Magyar Tudósok Körútja 2, H-1117 Budapest, HungaryMaternity Private Clinic of Obstetrics and Gynecology, H-1126 Budapest, HungarySystems Biology of Reproduction Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Magyar Tudósok Körútja 2, H-1117 Budapest, HungarySystems Biology of Reproduction Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Magyar Tudósok Körútja 2, H-1117 Budapest, HungaryDepartment of Obstetrics and Gynecology, Medical School, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Obstetrics and Gynecology, Medical School, University of Debrecen, H-4032 Debrecen, HungarySystems Biology of Reproduction Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Magyar Tudósok Körútja 2, H-1117 Budapest, HungarySystems Biology of Reproduction Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Magyar Tudósok Körútja 2, H-1117 Budapest, HungaryDepartment of Pharmacology and Pharmacotherapy, Medical School, University of Debrecen, H-4032 Debrecen, HungaryFaculty of Health and Sport Sciences, Széchenyi István University, H-9026 Győr, HungaryDepartment of Obstetrics and Gynecology, Medical School, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pharmacology, Monash Biomedicine Discovery Institute, Clayton 3168, AustraliaDepartment of Obstetrics and Gynecology, Soroka University Medical Center, Ben Gurion University of the Negev, Be’er Sheva 8410501, IsraelMaternity Private Clinic of Obstetrics and Gynecology, H-1126 Budapest, HungaryDepartment of Obstetrics and Gynecology, Medical School, Semmelweis University, 27 Baross Street, H-1088 Budapest, HungarySystems Biology of Reproduction Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Magyar Tudósok Körútja 2, H-1117 Budapest, HungaryMiscarriages 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 (<i>n</i> = 14) and controls undergoing elective termination of pregnancy (<i>n</i> = 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.https://www.mdpi.com/1422-0067/25/3/1865bioinformaticshabitual abortionliquid biopsynon-invasive monitoringplacental proteinprenatal diagnostics |
| spellingShingle | Eszter Tóth Dániel Györffy Máté Posta Petronella Hupuczi Andrea Balogh Gábor Szalai Gergő Orosz László Orosz András Szilágyi Orsolya Oravecz Lajos Veress Sándor Nagy Olga Török Padma Murthi Offer Erez Zoltán Papp Nándor Ács Nándor Gábor Than Decreased Expression of Placental Proteins in Recurrent Pregnancy Loss: Functional Relevance and Diagnostic Value International Journal of Molecular Sciences bioinformatics habitual abortion liquid biopsy non-invasive monitoring placental protein prenatal diagnostics |
| title | Decreased Expression of Placental Proteins in Recurrent Pregnancy Loss: Functional Relevance and Diagnostic Value |
| title_full | Decreased Expression of Placental Proteins in Recurrent Pregnancy Loss: Functional Relevance and Diagnostic Value |
| title_fullStr | Decreased Expression of Placental Proteins in Recurrent Pregnancy Loss: Functional Relevance and Diagnostic Value |
| title_full_unstemmed | Decreased Expression of Placental Proteins in Recurrent Pregnancy Loss: Functional Relevance and Diagnostic Value |
| title_short | Decreased Expression of Placental Proteins in Recurrent Pregnancy Loss: Functional Relevance and Diagnostic Value |
| title_sort | decreased expression of placental proteins in recurrent pregnancy loss functional relevance and diagnostic value |
| topic | bioinformatics habitual abortion liquid biopsy non-invasive monitoring placental protein prenatal diagnostics |
| url | https://www.mdpi.com/1422-0067/25/3/1865 |
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