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Keywords = placental thickness

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17 pages, 6114 KB  
Article
Maternal Administration of Aripiprazole Impedes the Appendicular Skeletal Growth of Rat Fetuses: A Teratological and Histomorphometrical Assessment
by Bhagath Kumar Potu, Mariwan Husni, Wael Amin Nasr El-Din, Abdel Halim Salem, Aisha Rashid, Amer Almarabheh and Raouf Abdelrahman Fadel
Biomedicines 2026, 14(6), 1294; https://doi.org/10.3390/biomedicines14061294 - 6 Jun 2026
Viewed by 282
Abstract
Background/Objectives: A third-generation atypical antipsychotic drug, aripiprazole, is known to cross the placental barrier and pose negative consequences on placental growth and the normal development of the fetus. Although a few studies demonstrated these debilitating effects of aripiprazole, its skeletal effects remain [...] Read more.
Background/Objectives: A third-generation atypical antipsychotic drug, aripiprazole, is known to cross the placental barrier and pose negative consequences on placental growth and the normal development of the fetus. Although a few studies demonstrated these debilitating effects of aripiprazole, its skeletal effects remain unexplored. Therefore, this study was undertaken to evaluate the impact of prenatal aripiprazole exposure, administered at three different dose levels, on the ossification of the appendicular skeleton in 20-day-old rat fetuses. Methods: Forty pregnant Sprague–Dawley rats (n = 40) were assigned to four groups: control and three aripiprazole-treated groups receiving 3 mg/kg (LDA), 6 mg/kg (HDA), and 12 mg/kg (DHDA) daily from gestational days 6–19. Fetuses were delivered on gestation day 20, weighed, and processed for skeletal evaluation using Alizarin Red S staining. Ossification patterns of metacarpals, metatarsals, hip bones, long bones of the forelimb and hindlimbs from a total of 151 fetuses were analyzed and categorized as complete, delayed, or absent. Results: Aripiprazole exposure induced a dose-dependent reduction in the number of completely ossified skeletal bony centers (p < 0.01) with a highly significant reduction in the length of ossified portions of the long bones (p < 0.001). Histomorphometric analysis of Von Kossa-stained fetal femur sections revealed a significant decrease in the thickness of ossified cortical and trabecular bone with a statistically significant reduction in the length of hypertrophied chondrocytes of the growth plate cartilage in the aripiprazole-treated groups (p < 0.05). Conclusions: Prenatal exposure to aripiprazole leads to dose-dependent skeletal growth restriction and delayed ossification of the appendicular skeleton in rat fetuses. Future investigations should focus on the molecular mechanisms and consequences related to the prenatal impact of aripiprazole. Full article
(This article belongs to the Section Cell Biology and Pathology)
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19 pages, 2212 KB  
Article
Vascular Endothelial Growth Factor and Placental Growth Factor in Conjunction with Vascular Endothelial Growth Factor Receptor-1 May Exert Dual Effects Within the Kidney and Brain in Patients with Type 2 Diabetes Mellitus and Normoalbuminuric Diabetic Kidney Disease
by Ligia Petrica, Florica Gadalean, Adrian Vlad, Daliborca Vlad, Victor Dumitrascu, Tutac Paul, Flaviu Bob, Oana Milas, Anca Suteanu-Simulescu, Mihaela Glavan, Sorin Ursoniu, Lavinia Balint-Marcu, Maria Mogos-Stefan, Silvia Ienciu, Octavian Marius Cretu, Roxana Popescu, Cristina Gluhovschi, Lavinia Iancu and Dragos Catalin Jianu
Int. J. Mol. Sci. 2026, 27(9), 3752; https://doi.org/10.3390/ijms27093752 - 23 Apr 2026
Viewed by 389
Abstract
The kidney and the brain share similarities in terms of structure and haemodynamic regime. The aim of the study was to assess a potential correlation of vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor-1 (sFlt-1), and placental growth factor (PlGF) [...] Read more.
The kidney and the brain share similarities in terms of structure and haemodynamic regime. The aim of the study was to assess a potential correlation of vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor-1 (sFlt-1), and placental growth factor (PlGF) with biomarkers of podocyte damage, proximal tubular (PT) dysfunction, and endothelial dysfunction, as well as with cerebral vessels haemodynamic indices in neurologic asymptomatic type 2 DM patients. A cohort of 212 patients diagnosed with type 2 DM and 49 age- and gender-matched healthy controls were enrolled in the study. Parameters studied were urinary albumin/creatinine ratio (UACR), biomarkers of podocyte damage (synaptopodin, podocalyxin), PT dysfunction (kidney injury molecule-1-KIM-1, N-acetyl-β-(D)-glucosaminidase-NAG), endothelial dysfunction (P-selectin), VEGF, sFlt-1, and PlGF. The cerebrovascular hemodynamic indices evaluated were intima–media thickness (IMT) in the common carotid arteries (CCAs), the pulsatility index (PI), and the resistivity index (RI) in the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs). Cerebrovascular reactivity (CVR) was assessed by the breath-holding index (BHI). In multivariable regression analysis, serum VEGF correlated directly with UACR, synaptopodin, NAG, serum P-selectin; serum sFlt-1 correlated directly with UACR, synaptopodin, podocalyxin, NAG, KIM-1; serum PlGF correlated negatively with eGFR and directly with UACR, synaptopodin, KIM-1. IMT-CCA correlated indirectly with eGFR and directly with UACR, serum P-selectin, and serum sFlt-1. The PI-ICAs correlated negatively with eGFR and positively with UACR, synaptopodin, serum P-selectin, and serum sFlt-1. The PI-MCAs correlated indirectly with eGFR and directly with synaptopodin, serum P-selectin, and serum sFlt-1. The RI-ICAs had a negative correlation with eGFR and a positive one with UACR, synaptopodin, NAG, KIM-1, urinary sFlt-1, and serum PlGF. The RI-MCAs displayed an indirect correlation with eGFR and a direct correlation with NAG, KIM-1, and serum sFlt-1. The BHT correlated directly with eGFR and negatively with serum P-selectin and serum PlGF. The study shows a significant association of VEGF, sFlt-1, and PlGF with biomarkers of podocyte injury, PT dysfunction, and endothelial dysfunction in early stages of DKD. These pro-angiogenic and anti-angiogenic factors correlated with cerebrovascular haemodynamic indices in neurologic asymptomatic type 2 DM, even in the normoalbuminuric stage of diabetic kidney disease. Full article
(This article belongs to the Special Issue Molecular Aspects of Diabetes and Its Complications)
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15 pages, 507 KB  
Article
Altered PAPP-A and Placental Thickness in Pre-Eclampsia and Intrauterine Growth Restriction: A Pilot Study
by Liviu Moraru, Raluca Moraru, Melinda Ildiko Mitranovici and Romeo Micu
J. Clin. Med. 2026, 15(4), 1607; https://doi.org/10.3390/jcm15041607 - 19 Feb 2026
Viewed by 856
Abstract
Pre-eclampsia (PE) is a multisystem disorder that affects 5–6% of all pregnancies. Background: PE and intrauterine growth restriction (IUGR) are two major causes of maternal mortality and morbidity. We hypothesize that first-trimester pregnancy-associated plasma protein-A (PAPP-A) levels are useful as a prognostic [...] Read more.
Pre-eclampsia (PE) is a multisystem disorder that affects 5–6% of all pregnancies. Background: PE and intrauterine growth restriction (IUGR) are two major causes of maternal mortality and morbidity. We hypothesize that first-trimester pregnancy-associated plasma protein-A (PAPP-A) levels are useful as a prognostic marker. The aim of our study is to identify the role of PAPP-A and placental thickness in pre-eclampsia screening, as well as its value in IUGR prognosis. Methods: This prospective study was conducted at the Al. Simionescu County Hospital Hunedoara, Romania, Department of Obstetrics and Gynecology, from 12 May to 31 October 2025. A total of 102 patients were included in our study; of these, 28 patients (28.56%) developed pre-eclampsia, and 13 (13.26%) developed IUGR associated with PE. Results: The demographic data showed no differences between groups, except for BMI, smoking habits, and diabetes mellitus. Of the 28 cases of pre-eclampsia, 14.28% had PE detected by 28 weeks, 46.4% had PE associated with IUGR by 33/34 weeks, and 39.32% had PE detected at term/delivery. The highest detection rate was at 33/34 weeks, when the association with IUGR was obvious. For PE with IUGR at 34 weeks, the area under the curve (AUC) was 0.909, with a p-value < 0.001. The PAPP-A cut-off was 0.65 MoM, indicating high sensitivity and specificity for predicting PE. Placental thickness was also assessed, resulting in statistically significant differences between groups. The PAPP-A level shows strong predictive value for PE, especially when associated with placental thickness. Conclusions: This study demonstrates a clear correlation between low PAPP-A in the first trimester of pregnancy, placental thickness in the second trimester, and the subsequent development of pre-eclampsia and its association with IUGR. Full article
(This article belongs to the Special Issue Innovations in Preeclampsia)
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20 pages, 3317 KB  
Article
Study on the Effect of N-Carbamylglutamate (NCG) on Reproductive Performance and Regulation Mechanism of Primary Lake Sheep
by Tianli Gao, Chunyang Li, Juanshan Zheng, Yingpai Zhaxi, Yuan Cai, Rongxin Zang, Huixia Liu, Yanmei Yang, Sai Li, Xiaodi Shi and Chen Huang
Animals 2026, 16(3), 464; https://doi.org/10.3390/ani16030464 - 2 Feb 2026
Viewed by 1058
Abstract
The aim of this study was to investigate the effects of dietary supplementation with 0.11% N-carbamylglutamate (NCG) during early pregnancy (0–90 days) on reproductive performance and fetal development, and to elucidate the underlying placental regulatory mechanisms in primiparous Hu sheep. Twenty-two 10-month-old sexually [...] Read more.
The aim of this study was to investigate the effects of dietary supplementation with 0.11% N-carbamylglutamate (NCG) during early pregnancy (0–90 days) on reproductive performance and fetal development, and to elucidate the underlying placental regulatory mechanisms in primiparous Hu sheep. Twenty-two 10-month-old sexually mature primiparous Hu sheep meeting the mating criteria were randomly assigned to two groups. The control group was fed a basal diet, while the NCG group received the basal diet supplemented with 0.11% NCG, with both feeding regimens maintained for 90 days. By measuring uterine and fetal growth indices, maternal plasma biochemical parameters, and amino acid levels, as well as assessing cotyledon indices and observing cotyledon morphology and histological structure, basic data related to placental function and fetal growth in pregnant ewes was collected. Combined with transcriptomic sequencing of maternal placental tissue, the mechanism by which NCG influences placental function and fetal growth and development in pregnant ewes was further investigated. The supplementation of NCG could increase the number of fetuses, total weight of fetuses, the number of corpus luteum and the ratio of fetuses to corpus luteum, but the difference was not significant (p > 0.05). The levels of plasma NO, inducible Nitric Oxide Synthase (iNOS) and several amino acids were significantly increased (p < 0.05). In ewes’ uteri, the average uterine weight, number of uterine glands, total cotyledon weight, and average weight per cotyledon were significantly increased (p < 0.05), whereas uterine mucosal thickness was markedly decreased. The Quantitative Real-time PCR (q-PCR) results for differentially expressed genes were consistent with those of transcriptomic analysis, showing significant changes in the expression levels of certain differentially expressed genes in maternal placental tissues. These changes regulated pathways such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), phosphatidylinositol 3-kinase–protein kinase B (PI3K–AKT) signaling pathways and Mitogen-Activated Protein Kinase (MAPK) pathway, which are involved in angiogenesis, energy supply and metabolism, and somatic growth and development. Dietary supplementation with NCG during early pregnancy can significantly improve the reproductive performance of primiparous Hu sheep, optimize the intrauterine environment and nutrient supply, and thereby facilitate pregnancy maintenance and fetal development. The underlying mechanism may involve promoting endogenous arginine synthesis in ewes, increasing plasma levels of NO, arginine, and certain amino acids, which collectively validate the positive effects of NCG on the reproductive performance and growth of Hu sheep during early pregnancy at the molecular level. Full article
(This article belongs to the Section Animal Reproduction)
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16 pages, 1057 KB  
Article
Combined Therapy Versus Fortified Anti-VEGF Monotherapy in Type C Polypoidal Choroidal Vasculopathy: Long-Term Outcomes and Exploratory Biomarker Insights
by Windsor Wen-Jin Chao, Howard Wen-Haur Chao and Hsiao-Ming Chao
Int. J. Mol. Sci. 2026, 27(3), 1224; https://doi.org/10.3390/ijms27031224 - 26 Jan 2026
Viewed by 880
Abstract
While standard anti- vascular endothelial growth factor (VEGF) therapy, with or without photodynamic therapy (PDT), is effective for patients with polypoidal choroidal vasculopathy (PCV), not all achieve optimal visual outcomes. This study aimed to compare fortified (double the dose and the volume of [...] Read more.
While standard anti- vascular endothelial growth factor (VEGF) therapy, with or without photodynamic therapy (PDT), is effective for patients with polypoidal choroidal vasculopathy (PCV), not all achieve optimal visual outcomes. This study aimed to compare fortified (double the dose and the volume of the standard one) anti-VEGF combined with PDT versus fortified anti-VEGF monotherapy and to investigate biomolecular profiles and disease relationships among PCV, neovascular age-related macular degeneration (nvAMD), and central serous chorioretinopathy (CSCR). The goal was to identify novel pathways to inform future therapeutic strategies, including hypoxia-inducible factors (HIF)-1α inhibitors. This retrospective cohort study included 23 eyes with indocyanine green-confirmed type C PCV. One eye treated with transpupillary thermotherapy was not included in the following two groups. Patients received either combined therapy (PDT + fortified-dose anti-VEGF; n = 12) or fortified-dose anti-VEGF monotherapy (n = 10). Primary outcomes were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Secondary outcomes included injection burden and recurrence. Exploratory analyses examined aqueous biomarkers, including VEGF, placental growth factor (PlGF), β-catenin, HIF-1α, and Wnt1 across PCV, CSCR, and nvAMD to identify novel therapeutic targets. Significant (p = 0.003/p = 0.005) median CRT reduction was similar (p = 0.468) between groups (combined/monotherapy: 137.5 µm/106.5 µm). BCVA (median [Q1, Q3]) change in logarithm of the minimum angle of resolution (LogMAR) was not statistically significant (p = 0.279), with 0.25 [0.00, 0.98] in the combined group versus 0.00 [−0.03, 0.28] in the monotherapy group. Treatment burden of anti-VEGFs per person per year was lower with combined therapy (1.16 ± 0.47# PDT + 2.81 ± 0.92# anti-VEGF injections) compared with monotherapy (4.61 ± 1.49# injections). Six eyes demonstrated recurrence at a mean of 15.5 months. Incomplete regression of polyps and branching vascular networks was observed in all eyes. Exploratory biomarker analysis revealed significantly (p < 0.05) higher VEGF and PlGF levels in nvAMD compared with PCV. nvAMD also demonstrated significantly (p < 0.05) higher β-catenin and lower HIF-1α levels relative to PCV and CSCR, while no significant biomarker differences were observed between PCV and CSCR. Combined therapy or monotherapy with fortified anti-VEGFs reduced treatment burden and achieved significant anatomical improvement but did not yield superior functional outcomes, highlighting the therapeutic difficulty of type C PCV. Biomarker profiling revealed shared hypoxia-related mechanisms between PCV and CSCR, with elevated HIF-1α compared to nvAMD indicating a “preliminary” possible role for HIF-1α inhibitors. Differential expression of these biomarkers highlights additional molecular pathways that may inform future targeted interventions. Full article
(This article belongs to the Special Issue Molecular Insight into Retinal Diseases: 2nd Edition)
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15 pages, 2388 KB  
Article
Placental Thickness Correlates with Severity-Weighted Fetal Dysfunction in the Third Trimester
by Julia Murlewska, Oskar Sylwestrzak, Iwona Strzelecka, Łukasz Sokołowski, Paulina Kordjalik, Maciej Słodki and Maria Respondek-Liberska
J. Clin. Med. 2025, 14(21), 7461; https://doi.org/10.3390/jcm14217461 - 22 Oct 2025
Viewed by 1727
Abstract
Background: Placental thickness has been associated with adverse perinatal outcomes, but the relationship to specific fetal abnormalities seems to not yet be well understood. This study investigates whether increased placental thickness correlates with the severity of fetal cardiac and extracardiac conditions using a [...] Read more.
Background: Placental thickness has been associated with adverse perinatal outcomes, but the relationship to specific fetal abnormalities seems to not yet be well understood. This study investigates whether increased placental thickness correlates with the severity of fetal cardiac and extracardiac conditions using a structured classification and severity-weighted scoring system. Methods: We undertook a retrospective analysis of 1452 fetal echocardiograms conducted during the third trimester at a tertiary referral institution from the years 2022 to 2025. The diagnoses were categorized into four distinct classifications: congenital heart anomalies, cardiac dysfunctions, extracardiac malformations, and extracardiac dysfunctions. Each diagnostic category was allocated a severity weight predicated on established fetal and neonatal mortality risk literature. The evaluation of placental thickness was regarded not merely as a persistent variable but also categorized into three distinct classifications: thin (≤40 mm), intermediate (41–69 mm), and thick (≥70 mm). The examination of correlations was performed utilizing Spearman’s ρ; comparative evaluations among the groups were conducted employing the Kruskal–Wallis and Mann–Whitney U tests. Results: Placental thickness revealed a moderate positive correlation with weighted extracardiac dysfunctions (ρ = 0.36, p < 0.00001), displayed a comparatively weaker yet statistically significant association with cardiac dysfunctions (ρ = 0.13, p = 0.01). Fetuses identified by increased placental thickness (≥70 mm) exhibited notably higher mean scores for both cardiac and extracardiac dysfunctions. Within the cohort exhibiting thick placentas, 25.8% displayed extracardiac dysfunction scores surpassing 0.3, in contrast to only 7.7% within the cohort with thinner placentas. Conclusions: Augmented placental thickness correlates with an elevated cumulative load of fetal dysfunction, especially in the realms of extracardiac and functional cardiac impairments. The measurement of placental thickness may function as a straightforward, supplementary indicator of fetal distress in the third trimester, particularly when utilized alongside targeted imaging modalities. Full article
(This article belongs to the Special Issue Clinical Advances in Prenatal Diagnosis and Fetal Therapy)
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20 pages, 3189 KB  
Communication
Native Wound-Repair Proteins Retained in Multilayer Placental CAMPs
by Pragya Singh, Shantanu Guha, Odalis Landa, Andrew Ryan King, Diego Valdes Cavazos, Joanna Marquez and Shauna Hill
Int. J. Mol. Sci. 2025, 26(20), 10121; https://doi.org/10.3390/ijms262010121 - 17 Oct 2025
Viewed by 1161
Abstract
The human placenta is a complex organ that supports fetal development and is rich in extracellular matrix proteins and growth factors, making it suitable as a biomaterial in wound care. Placenta-derived amnion-only allografts have traditionally been used in the clinic, but they lack [...] Read more.
The human placenta is a complex organ that supports fetal development and is rich in extracellular matrix proteins and growth factors, making it suitable as a biomaterial in wound care. Placenta-derived amnion-only allografts have traditionally been used in the clinic, but they lack the structural and biochemical complexity of the full three-layer placental membrane, which includes the amnion, intermediate, and chorion layers. Advances in tissue engineering have enabled preservation of multiple layers, giving rise to multilayer placental-based Cellular and Acellular Matrix-like Products (CAMPs) such as Full-Thickness (FT; amnion, intermediate, chorion) and ACA (amnion, intermediate, chorion, amnion). Although these advanced CAMPs are increasingly applied clinically, their molecular composition has not been comprehensively defined. This study presents a global proteomic analysis of FT and ACA, complemented by targeted multiplex analysis of soluble proteins and an in vitro angiogenesis assay. Proteomic profiling identified 8908 structural and bioactive components, with 32.5% of proteins associated with tissue repair and remodeling pathways. Multiplex analysis confirmed accessibility of biologically relevant soluble factors. Endothelial tube formation assays further supported biological relevance, demonstrating that soluble proteins in FT and ACA support angiogenesis. These data provide a molecular characterization of multilayer CAMPs and underscore their potential to deliver durable wound coverage while supporting the local microenvironment. Full article
(This article belongs to the Special Issue Molecular and Cellular Perspectives on Wound Healing)
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15 pages, 533 KB  
Article
Placental Growth Factor and Female Long-Term Hypertension
by Maria C. Adank, Jeanine E. Roeters Van Lennep, Laura Benschop, James M. Roberts, Robin E. Gandley, Yolanda B. De Rijke, Eric A. P. Steegers and Sarah Schalekamp-Timmermans
J. Clin. Med. 2025, 14(19), 6751; https://doi.org/10.3390/jcm14196751 - 24 Sep 2025
Viewed by 1615
Abstract
Background and Aims: Placental growth factor (PlGF) is an important predictive marker of pregnancy complications such as preeclampsia. The aim of this study is to assess whether PlGF measured outside of pregnancy is a predictive marker for cardiovascular disease (CVD) risk in young [...] Read more.
Background and Aims: Placental growth factor (PlGF) is an important predictive marker of pregnancy complications such as preeclampsia. The aim of this study is to assess whether PlGF measured outside of pregnancy is a predictive marker for cardiovascular disease (CVD) risk in young women. Methods: This study was embedded in the Generation R Study, a population-based prospective cohort study. PlGF concentrations, as well as systolic and diastolic blood pressure (SBP and DBP), cardiac outcomes, carotid-femoral pulse wave velocity, and central retinal arteriolar and venular calibres of 5077 women, were assessed six years after pregnancy, which was considered baseline. Four years after baseline, we measured blood pressure and intimal media thickness (IMT). Eight years after baseline, we measured blood pressure and the post-occlusive reactive hyperaemia index (PORH index). In addition, we examined the influence of pregnancy complications on these associations. Results: We found a positive association between PlGF levels with SBP (0.46, 95% CI 0.04; 0.89). PlGF was not associated with retinal or echocardiographic measurements. PlGF was positively associated with DBP after four years and with both SBP and DBP eight years after baseline, independent of the occurrence of pregnancy complications. PlGF was not associated with IMT or the PORH index. Conclusions: PlGF is associated with higher blood pressure. PlGF may, therefore, be used as a marker of hypertension. These results need to be replicated in an independent cohort study. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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14 pages, 633 KB  
Review
A Systematic Review on Biomarkers for Gestational Diabetes Mellitus Detection in Pregnancies Conceived Using Assisted Reproductive Technology: Current Trends and Future Directions
by Angeliki Gerede, Efthymios Oikonomou, Anastasios Potiris, Christos Chatzakis, Peter Drakakis, Ekaterini Domali, Nikolaos Nikolettos and Sofoklis Stavros
Int. J. Mol. Sci. 2025, 26(17), 8234; https://doi.org/10.3390/ijms26178234 - 25 Aug 2025
Cited by 2 | Viewed by 2755
Abstract
Gestational diabetes mellitus (GDM) is a frequently encountered medical complication during pregnancy that is increasing at a rapid pace globally, posing significant public health concerns. Similarly, there is a rising trend in the number of women who have utilized assisted reproductive technology (ART). [...] Read more.
Gestational diabetes mellitus (GDM) is a frequently encountered medical complication during pregnancy that is increasing at a rapid pace globally, posing significant public health concerns. Similarly, there is a rising trend in the number of women who have utilized assisted reproductive technology (ART). Numerous studies have been carried out to investigate the relationship between GDM and ART. This comprehensive systematic review seeks to identify potential biomarkers for the early diagnosis of GDM in pregnancies conceived through ART. We conducted a PubMed search covering the past five years to identify studies that explore biomarkers associated with the development of GDM in pregnancies conceived through ART. The outcome measures included human chorionic gonadotropin (HCG), the body mass index (BMI), the Follicle Stimulating Hormone to Luteinizing Hormone (FSH/LH) ratio, increased hemoglobin A1c levels, fasting insulin concentrations, homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride levels, total cholesterol levels, low-density lipoprotein cholesterol concentrations, low-density lipoprotein/high-density lipoprotein (LDL/HDL), total cholesterol to high-density lipoprotein (TC/HDL), the estradiol/follicle ratio, soluble fms-like tyrosine kinase-1 (sFlt-1), Placental Growth Factor (PLGF), endometrial thickness, and psychological stress. Seventeen studies were included. The identification and development of serum or ultrasound biomarkers for the early detection of GDM in pregnancies conceived through ART pose considerable challenges. These challenges arise from the multifactorial nature of GDM, the methodological variations in ART, and the limited availability of relevant studies. The most promising biomarker identified was the estradiol/follicle ratio. Women with a higher estradiol/follicle ratio exhibited significantly lower rates of GDM. There is a pressing necessity for biomarkers to enable the early detection of GDM in pregnancies conceived through ART. E2 levels, β-hCG, and the E2/F ratio, along with the TC/HDL and LDL/HDL ratios, show potential as reliable biomarkers for identifying GDM. Full article
(This article belongs to the Special Issue Molecular Biomarkers for Targeted Therapies)
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13 pages, 544 KB  
Review
Ultrasound Assessment of Retained Products of Conception (RPOC): Insights from the Current Literature
by Giosuè Giordano Incognito, Carla Ettore, Orazio De Tommasi, Roberto Tozzi and Giuseppe Ettore
J. Clin. Med. 2025, 14(16), 5864; https://doi.org/10.3390/jcm14165864 - 19 Aug 2025
Cited by 5 | Viewed by 8718
Abstract
Retained products of conception (RPOC) represent a significant cause of morbidity in the post-abortive and postpartum periods, potentially leading to abnormal uterine bleeding, pelvic pain, infections, and intrauterine adhesions. Accurate diagnosis is crucial to avoid unnecessary surgical interventions and to preserve future fertility. [...] Read more.
Retained products of conception (RPOC) represent a significant cause of morbidity in the post-abortive and postpartum periods, potentially leading to abnormal uterine bleeding, pelvic pain, infections, and intrauterine adhesions. Accurate diagnosis is crucial to avoid unnecessary surgical interventions and to preserve future fertility. Transvaginal ultrasound constitutes the primary imaging modality for identifying RPOC, but the lack of standardized diagnostic criteria complicates clinical decision-making. This narrative review explores the current literature on sonographic findings associated with RPOC, focusing on the diagnostic value of endometrial thickness (ET), the presence of intrauterine echogenic masses, and the use of Color Doppler imaging. Although an ET ≥15 mm is frequently used to suspect RPOC, the variability in cut-off thresholds and limited specificity reduce its diagnostic reliability. The detection of an echogenic intrauterine mass appears to be the most sensitive and specific sonographic feature. Color Doppler assessment, particularly the presence of enhanced myometrial vascularity (EMV) and classification systems like the Gutenberg score, offers further insight by stratifying hemorrhagic risk and guiding therapeutic choices. However, vascular parameters such as peak systolic velocity (PSV) and resistive index (RI) demonstrate a substantial overlap between benign and pathological conditions, limiting their stand-alone utility. The review also addresses the differential diagnosis of RPOC, including blood clots, arteriovenous malformations, placental polyps, gestational trophoblastic disease, and endometrial osseous metaplasia. The role of three-dimensional ultrasound remains limited in clinical practice, offering no significant advantage over two-dimensional imaging. Finally, the timing of follow-up ultrasound after medical treatment with misoprostol is critical: delayed assessment reduces overtreatment by allowing time for spontaneous resolution. In conclusion, despite advances in ultrasound technology, the diagnosis of RPOC remains challenging due to heterogeneity in imaging findings and inter-observer variability. A multimodal approach integrating grayscale and Doppler ultrasound with clinical evaluation is essential for optimal management. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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14 pages, 3178 KB  
Article
The Role of β-Core Fragment hCG in Embryo Implantation and Early Pregnancy
by Ji Soo Ryu, Nu Ri Yang, Yu Ha Shim, Yu Jin Kim, Won Jae Kwag, Jin Dong Chang and Jae Ho Lee
Int. J. Mol. Sci. 2025, 26(16), 7974; https://doi.org/10.3390/ijms26167974 - 18 Aug 2025
Cited by 2 | Viewed by 4542
Abstract
Human chorionic gonadotropin (hCG) is a pregnancy biomarker, and five forms of this hormone are involved in female physiological regulation. β-core fragment hCG (bcf-hCG) is a fragment of hCG whose biological role in female reproduction has not been completely elucidated. This study aimed [...] Read more.
Human chorionic gonadotropin (hCG) is a pregnancy biomarker, and five forms of this hormone are involved in female physiological regulation. β-core fragment hCG (bcf-hCG) is a fragment of hCG whose biological role in female reproduction has not been completely elucidated. This study aimed to investigate its role in embryo implantation and maintenance of a pregnancy-supportive environment. We analyzed the protein expression pattern of bcf-hCG in the intrauterine environment during early pregnancy by performing western blotting and immunohistochemistry with a monoclonal anti-bcf-hCG antibody. We performed a cell proliferation assay in the presence of bcf-hCG compared with intact hCG. We conducted an ex vivo study by performing intrauterine injection of bcf-hCG or intact hCG in mice. Endometrial thickness was measured using histological methods, and uterine gene and protein expression were analyzed following intrauterine injection of bcf-hCG. We evaluated the effect of bcf-hCG on embryo implantation in the uterus. bcf-hCG was highly abundant in the placenta and epithelial stromal glands of the uterine endometrium during early pregnancy and significantly induced proliferation of a stromal epithelial cell line. Intrauterine injection of bcf-hCG induced expression of specific genes and proteins, including homeobox A10, for embryo implantation and placental development. Upon embryo transfer, the implantation rate of bcf-hCG-treated embryos was higher than that of control embryos. In conclusion, bcf-hCG plays a role in the proliferation of glandular epithelial cells in the endometrium and placenta during early pregnancy. Therefore, bcf-hCG is an early-phase pregnancy biomarker that maintains the initial phase of pregnancy. Full article
(This article belongs to the Special Issue Reproductive Endocrinology Research)
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15 pages, 2256 KB  
Communication
Comparative Study of Placental Allografts with Distinct Layer Composition
by Pragya Singh, Acarizia Easley, Karla Tapia Menchaca, Victor Fanniel, Raymond Gomez, Joanna Marquez and Shauna Hill
Int. J. Mol. Sci. 2025, 26(7), 3406; https://doi.org/10.3390/ijms26073406 - 5 Apr 2025
Cited by 4 | Viewed by 2772
Abstract
Human placental-derived allografts are biomaterials categorized as cellular, acellular, matrix-like products (CAMPs) that can serve as wound coverings due to placenta tissue’s innate barrier function. The placental membrane consists of three layers, the amnion, the intermediate layer (IL), and the chorion, each contributing [...] Read more.
Human placental-derived allografts are biomaterials categorized as cellular, acellular, matrix-like products (CAMPs) that can serve as wound coverings due to placenta tissue’s innate barrier function. The placental membrane consists of three layers, the amnion, the intermediate layer (IL), and the chorion, each contributing distinct functional and biological properties. This study investigates how variations in layer composition influence the Extracellular Matrix (ECM) and growth factor profiles of placental allografts. We compared Dual Layer (amnion–amnion), Full Thickness (amnion–intermediate–chorion, FT), and a novel four-layer allograft configuration (amnion–intermediate–chorion–amnion, ACA). Histological analyses using hematoxylin and eosin (H&E) and Masson’s trichrome staining revealed distinct structural architecture among the three allografts, with FT and ACA exhibiting 4.9 times and 5.7 times greater thickness as compared with the Dual Layer, respectively. Compositional studies revealed different concentrations of key ECM components (collagen, elastin, proteoglycans, hyaluronic acid) and growth factors (ANG-2, EGF, PDGF-AA, VEGF) across allografts. The collagen concentration was two times higher in ACA as compared with the Dual Layer and FT. Additionally, FT and ACA demonstrated higher levels of growth factors and other ECM components, underscoring their biochemical diversity. These findings highlight the fact that the structural and biochemical properties of placental-derived allografts depend on their layer composition. This study underscores the importance of tailoring layer configurations that are optimized for clinical applications of CAMPs, enabling clinicians to select the most suitable grafts for clinical use, such as for wound management. Full article
(This article belongs to the Special Issue Biomaterials for Wound Healing and Tissue Regeneration)
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24 pages, 7819 KB  
Article
Histological Changes in the Cat Placenta Throughout Gestation
by Gimena Gomez Castro, Rocío Hernández, Andrea Cristofolini, Enrique Portiansky, Cecilia Merkis, Erika Badura, Luciano Casas, Claudio Barbeito and Mónica Diessler
Vet. Sci. 2025, 12(3), 207; https://doi.org/10.3390/vetsci12030207 - 1 Mar 2025
Cited by 1 | Viewed by 7385
Abstract
This study on cat placental organogenesis provides a detailed histological description, emphasizing the stages that have been less described. Thirty-seven gestational sacs were obtained by ovariohysterectomy, and the gestational age of the embryos/fetuses was determined based on developmental characteristics. The placentas were measured [...] Read more.
This study on cat placental organogenesis provides a detailed histological description, emphasizing the stages that have been less described. Thirty-seven gestational sacs were obtained by ovariohysterectomy, and the gestational age of the embryos/fetuses was determined based on developmental characteristics. The placentas were measured and processed by routine histological techniques. Additionally, fresh tissue from a term placenta was processed for ultrastructural analysis. An in-depth histological analysis was performed, and several morphometric variables (placental and lamellar width, placental and labyrinthine thickness, area and number of decidual cells) were recorded and related mainly to gestational age. A significant increase was observed in fetal length from 31 dpc, while placental thickness rose until 39 dpc; lamellae became abundant, parallel, longer, and narrower. Many CTB cells gradually fused into the STB; however, it progressively reduced. Medium-sized decidual cells, arranged in groups at the junctional zone, were progressively incorporated into the lamellae; there, they persisted until term, decreasing in number and becoming larger and frequently binucleated. The description of temporal modifications in lamellar, trophoblastic, and decidual features widens current knowledge on feline placental morphogenesis. In addition, these findings might be valuable for elucidating mechanisms behind placental development, which in turn affect its efficiency. Full article
(This article belongs to the Section Anatomy, Histology and Pathology)
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16 pages, 3861 KB  
Review
What Is the Significance of Placental Lakes in Pregnancy? A Historic Literature Review
by Joanna Choi-Klier, Stephanie Masters, Danielle Lewis, Kaitlyn Taylor and Everett F. Magann
J. Clin. Med. 2025, 14(4), 1260; https://doi.org/10.3390/jcm14041260 - 14 Feb 2025
Viewed by 6192
Abstract
Background/Objectives: The presence of placental lakes has been recognized on obstetric ultrasounds for many years, although their influence on pregnancy and perinatal outcomes remains uncertain. Most studies evaluating outcomes are small and many outcomes are conflicting. The question remains whether placental lakes affect [...] Read more.
Background/Objectives: The presence of placental lakes has been recognized on obstetric ultrasounds for many years, although their influence on pregnancy and perinatal outcomes remains uncertain. Most studies evaluating outcomes are small and many outcomes are conflicting. The question remains whether placental lakes affect pregnancy outcomes and, if so, how and under what circumstances? The purpose of this review was to determine the incidence, diagnosis, pathology, management, and pregnancy outcomes to determine the influence of an isolated lake versus the influence of a lake with the presence of other factors on pregnancy and perinatal outcomes. Methods: Electronic databases (PubMed, OVID, CINAHI, Embase, and Web of Science) were searched. The only limitation was the abstract/paper had to be in English. The search years were 1980–2023. The search terms included “placenta lake” AND “pregnancy outcomes”. Results: Of 323 abstracts identified, 26 full articles were selected as the basis of this review. A number of adverse outcomes have been reported with placenta lakes, including hypertensive disorders of pregnancy, fetal growth restriction, and intrauterine fetal demise. Other studies reported no adverse outcomes. A number of factors in addition to the placental lake, such as the size of the lake, number of lakes, and presence of a thick placenta, might increase the risk of adverse outcomes. Conclusions: Unfavorable pregnancy outcomes may be related to placental lakes, particularly if the lakes are multiple and large and the placenta is thick. Additional large studies are needed to determine if antenatal surveillance is helpful. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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16 pages, 2923 KB  
Article
The Effect of Maternal Obesity on Placental Autophagy in Lean Breed Sows
by Liang Tian, Fen Su, Xueyi Zhu and Xingyue Zou
Vet. Sci. 2025, 12(2), 97; https://doi.org/10.3390/vetsci12020097 - 27 Jan 2025
Cited by 3 | Viewed by 2281
Abstract
This study aimed to evaluate the influence of back-fat thickness (BF), at mating of sows, on autophagy in placenta and the potential mechanism. The sows were divided into two groups according to their BF at mating: BFI (15–20 mm, n = 14) and [...] Read more.
This study aimed to evaluate the influence of back-fat thickness (BF), at mating of sows, on autophagy in placenta and the potential mechanism. The sows were divided into two groups according to their BF at mating: BFI (15–20 mm, n = 14) and BFII (21–27 mm, n = 14) as the maternal obesity group. The placental samples used for investigating autophagic function and fatty acid profiles were obtained by vaginal delivery. Our results demonstrated that autophagy defects were observed in placenta from BFII sows along with altered circulating and placental fatty acid profiles. Indicative of impaired autophagy, reduced autophagic vesicles as well as LC3-positive puncta were linked to decreased mRNA or protein expression of autophagy-related genes, including ATG5, ATG7, Beclin1, ATG12, LC3, LAMP1 and LAMP2 in the placenta of BFII sows (p < 0.05). Meanwhile, we found reduced conversion of LC3-I to LC3-II and up-regulated protein content of p62 in the placenta from BFII group (p < 0.05). Furthermore, excessive back-fat was also associated with increased activation of AKT/mTOR signaling and decreased mRNA content of transcription factors regulating the autophagic pathway, including PPARα and PGC1α, but increased mRNA expression of NcoR1 in placenta. Together, these findings indicate that maternal obesity incites autophagy injury in pig term placenta, which may contribute to augmented placental lipid accumulation and therefore impaired placental function. Full article
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