Search Results (60)

The aim of this study was to evaluate the effect of the linoleic–α-linolenic acid ratio (LA:ALA) on cyclicity, oocyte quality, early pregnancy parameters, milk yield, and composition. Holstein cows were randomized to a 6:1-LA:ALA diet (Low-OMG3: n = 3 pens; 11 primiparous, 14 multiparous) or a 2:1-LA:ALA diet (High-OMG3: n = 3 pens; 10 primiparous, 14 multiparous). Diets were isocaloric and isonitrogenous and fed between 15 and 140 days in milk (DIM). Data were compared using linear mixed models. As expected, omega-3 concentrations in milk and blood increased in the High- compared to Low-OMG3 cows. No effect of diet was observed on cyclicity by 45DIM or oocyte quality at 50DIM. High-OMG3 cows had larger corpus luteum size (11–32 d post-timed artificial insemination [TAI]) and greater blood flow (32–60 d post-TAI) than Low-OMG3 cows. However, there was no effect of diet on progesterone, pregnancy-associated glycoproteins, or conceptus size. High-OMG3 cows produced more milk throughout the study, had greater lactose, and tended to have greater protein yield at 50DIM. In conclusion, decreasing the LA:ALA dietary ratio in lactating dairy cows did not provide evidence of effects on cyclicity, oocyte quality, or other early pregnancy-related parameters, but affected corpus luteum size and blood flow, enhanced milk production, and partially increased protein and lactose yields. Full article

The proteins most frequently associated with pregnancy are the pregnancy-associated glycoproteins (PAGs), which are abundantly expressed placental products in species belonging to the order Cetartiodactyla. Multiple PAG isoforms are expressed across different species and stages of gestation, with their expression influenced by factors, such as breed and bodyweight. These proteins can be detected in both blood and milk samples using ELISA or RIA assays, serving as early indicators of pregnancy. The present study aimed to detect PAGs in caprine milk through a non-invasive, high-throughput, mass-spectrometry-based proteomic approach. Milk samples were collected from 20 Skopelos breed goats at 20 and 45 days post-mating. Following appropriate processing for whey protein extraction, the samples underwent tryptic digestion to generate peptides for LC-MS/MS analysis. The proteomic investigation identified five distinct PAGs (caPAG₂ on day 20 and caPAG₃, caPAG₅, caPAG₆, and caPAG₁₂,on day 45 post-mating) annotated to Capra hircus, along with 22 additional proteins associated with the fetal–maternal interface, pregnancy progression, and immune-related pathways. These findings demonstrate that LC-MS/MS provides a non-invasive, sensitive, and reliable method for detecting PAGs in caprine milk during the early stages of pregnancy (day 20, as the presence of caPAG₂ revealed), applicable to both individual animals and flock-level monitoring. Full article

Background: Gestational hypertension (GHT) is associated with adverse maternal and perinatal outcomes, and reliable biomarkers for risk stratification remain limited. Thrombospondin-4 (TSP-4), a matricellular glycoprotein implicated in vascular remodeling, may play a role in hypertensive disorders of pregnancy. This study aimed to investigate maternal serum TSP-4 levels in GHT and their associations with obstetric and neonatal outcomes. Methods: This prospective cohort study included 44 women with GHT and 44 normotensive controls. Maternal serum TSP-4 levels were measured between 20–30 weeks’ gestation, and demographic, obstetric, and neonatal data were recorded. The development of preeclampsia (PE) and composite adverse perinatal outcomes (CAPO) was subsequently compared between the groups. Results: TSP-4 levels were significantly higher in the GHT group compared with controls (9.50 vs. 7.92 ng/mL, p < 0.001). Women with GHT had lower gestational age at delivery and birth weight, with higher rates of preterm delivery, fetal distress, NICU admission, and composite adverse perinatal outcomes (all p < 0.01). Within the GHT group, patients who developed PE had notably higher TSP-4 levels (13.45 vs. 9.33 ng/mL, p < 0.001). Conclusions: Elevated maternal serum TSP-4 is independently associated with GHT and progression to PE. TSP-4 may serve as a novel biomarker for risk assessment in hypertensive disorders of pregnancy. Full article

Background/Objectives: Classified as a hypertensive disorder of pregnancy, preeclampsia is one of the leading causes of maternal and fetal morbidity and mortality. The abnormal trophoblast invasion that leads to a failed transformation of the uterine spiral arteries during placentation remains the most probable cause for preeclampsia. It is known that adiponectin acts on the placenta, playing a regulatory role in placentation processes. Therefore, the aim of this systematic review is to compile scientific evidence to evaluate the role of adiponectin as a biomarker for preeclampsia. Methods: The protocol for this systematic review was registered on the PROSPERO database (ID CRD42024542403) and follows the PRISMA 2020 guidelines. Overall, twenty-nine studies were selected from the PubMed and Scopus databases, including case–control, prospective and retrospective cohort, cross-sectional, and bidirectional Mendelian randomization studies. Results: From the articles analyzed, nine studies indicated an increase in adiponectin levels in preeclampsia, eleven reported a decrease, eight detected no significant changes, and in two studies, it was not possible to determine the glycoprotein levels. Analysis of the evidence quality revealed that moderate and low evidence levels predominate, with stronger evidence for decreased adiponectin levels. Conclusions: Promoting the advancement of scientific research is crucial, particularly exploring the association between adiponectin and other biomarkers. This approach could facilitate the development of screening and diagnostic methods, enabling the implementation of specific preventive and therapeutic strategies. Full article

Background: Preterm birth (PTB) remains a leading cause of neonatal morbidity and mortality worldwide. Inflammatory cytokines, particularly IL-6, are central to PTB pathogenesis. Lactoferrin (LF), an iron-binding glycoprotein with antimicrobial and immunomodulatory properties, has been proposed as a potential protective factor against PTB. This narrative review aimed to synthesize current evidence on LF supplementation and its effects on inflammation, cytokine modulation, biochemical markers, and obstetric outcomes related to PTB. Methods: Eight clinical studies involving pregnant women at risk of PTB were included. LF was administered orally, vaginally, or through combined regimens, with variations in dosage and duration. Reported outcomes encompassed inflammatory markers, cervical and uterine parameters, oxidative stress biomarkers, and obstetric or neonatal endpoints. Results: Across the studies, LF supplementation was consistently associated with reduced pro-inflammatory cytokines, improvements in cervical length and uterine activity, and favorable changes in oxidative stress markers. Clinically, supplementation was linked with prolonged gestation, fewer preterm births, and reduced neonatal intensive care admissions. Immunological analyses further suggested a positive modulation of cytokine profiles in amniotic fluid. Conclusions: LF appears to exert multifaceted immunomodulatory effects that mitigate inflammation and support pregnancy maintenance. Although findings point to its potential role in PTB prevention, they should be interpreted with caution given the limited and heterogeneous evidence. Further large-scale, multicenter randomized trials are needed to confirm efficacy and to establish optimal dosage, route, and timing of administration. Full article

Background/Objectives: Fetuin-A is a multifunctional glycoprotein involved in metabolic and inflammatory regulation. Although its role in insulin resistance, type 2 diabetes, and cardiovascular disease is well recognized, its relationship with pregnancy-related body mass changes remains unclear. This study aimed to explore associations between maternal BMI dynamics during and shortly after pregnancy and serum fetuin-A concentrations. Methods: Fifty-five healthy Caucasian women with term singleton pregnancies were enrolled. BMI was recorded at three time points: pre-pregnancy, before delivery, and 48 h postpartum. Based on ΔBMI (postpartum minus pre-pregnancy BMI), participants were divided into two groups: ΔBMI ≤ 1 kg/m² (n = 32) and ΔBMI > 1 kg/m² (n = 23). Serum fetuin-A levels were measured before delivery and postpartum using ELISA. Additional laboratory parameters and body composition were assessed postpartum via standard tests and bioelectrical impedance analysis (BIA). Results: No significant differences were found between groups in BMI at any single time point or in laboratory or BIA-derived parameters. However, all three BMI change indices (ΔBMI_gestational, ΔBMI_puerperal, and ΔBMI) differed significantly between groups. Fetuin-A concentrations did not differ significantly between groups. Importantly, fetuin-A levels decreased significantly after delivery in both groups, suggesting a potential role of the placenta in its regulation. A significant correlation was observed between pre-delivery fetuin-A and postpartum uric acid in Group ΔBMI > 1 kg/m² (p = 0.016), indicating a possible link in women with greater gestational weight gain. Conclusions: While fetuin-A was not directly associated with BMI changes, its peripartum dynamics and correlation with uric acid may reflect underlying metabolic-inflammation pathways. ΔBMI indices may offer a more individualized measure of weight dynamics in pregnancy research. Full article

Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more pregnancy losses before 20 weeks of gestation. RPL is a common medical condition among reproductive-age women, with approximately 23 million cases reported annually worldwide. Up to 5% of pregnant women may experience two or more consecutive pregnancy losses. Previous studies have investigated risk factors for RPL, including maternal age, uterine pathology, genetic anomalies, infectious agents, endocrine disorders, thrombophilia, and immune dysfunction. However, RPL is a disease caused by a complex interaction of genetic factors, environmental factors (e.g., diet, lifestyle, and stress), epigenetic factors, and the immune system. In addition, due to the lack of research on genetics research related to RPL, the etiology remains unclear in up to 50% of cases. Platelets play a critical role in pregnancy maintenance. This study examined the associations of platelet receptor and ligand gene variants, including integrin subunit beta 3 (ITGB3) rs2317676 A > G, rs3809865 A > T; fibrinogen gamma chain (FGG) rs1049636 T > C, rs2066865 T > C; glycoprotein 1b subunit alpha (GP1BA) rs2243093 T > C, rs6065 C > T; platelet endothelial cell adhesion molecule 1 (PECAM1) rs2812 C > T; and platelet endothelial aggregation receptor 1 (PEAR1) rs822442 C > A, rs12137505 G > A, with RPL prevalence. In total, 389 RPL patients and 375 healthy controls (all Korean women) were enrolled. Genotyping of each single nucleotide polymorphism was performed using polymerase chain reaction–restriction fragment length polymorphism and the TaqMan genotyping assay. All samples were collected with approval from the Institutional Review Board at Bundang CHA Medical Center. The ITGB3 rs3809865 A > T genotype was strongly associated with RPL prevalence (pregnancy loss [PL] ≥ 2: adjusted odds ratio [AOR] = 2.505, 95% confidence interval [CI] = 1.262–4.969, p = 0.009; PL ≥ 3: AOR = 3.255, 95% CI = 1.551–6.830, p = 0.002; PL ≥ 4: AOR = 3.613, 95% CI = 1.403–9.307, p = 0.008). The FGG rs1049636 T > C polymorphism was associated with a decreased risk in women who had three or more pregnancy losses (PL ≥ 3: AOR = 0.673, 95% CI = 0.460–0.987, p = 0.043; PL ≥ 4: AOR = 0.556, 95% CI = 0.310–0.997, p = 0.049). These findings indicate significant associations of the ITGB3 rs3809865 A > T and FGG rs1049636 T > C polymorphisms with RPL, suggesting that platelet function influences RPL in Korean women. Full article

Chromosomal microarray analysis (CMA) was performed for 40 patients with B-ALL undergoing treatment according to the ALL-2016 protocol to investigate the copy number alterations (CNAs) and copy neutral loss of heterozygosity (cnLOH) associated with minimal residual disease (MRD)-positive remission. Aberrations involving over 20,000 genes were identified, and a random forest approach was applied to isolate a subset of genes whose CNAs and cnLOH are significantly associated with poor therapeutic response. We have assembled the triple matched healthy population data and used that data as a reference, but not as a matched control. We identified a recurrent cluster of cnLOH in the 19q13.2–19q13.31 region, significantly enriched in MRD-positive patients (70% vs. 47% in the reference group vs. 16% in MRD-negative patients). This region includes the pregnancy-specific glycoprotein (PSG) gene family and the oncogene ERF, suggesting a potential role in leukemic persistence and treatment resistance. Additionally, we observed significant deletions involving 7p22.3 and 16q13, often as part of large-scale losses affecting almost the entire chromosomes 7 and 16, indicative of global chromosomal instability. These findings highlight specific genomic regions potentially involved in therapy resistance and may contribute to improved risk stratification in B-ALL. Our findings emphasize the value of high-resolution CMA in diagnostics and risk stratification and suggest that PSG genes and other candidate genes could serve as biomarkers for predicting treatment outcomes. Full article

This study evaluated the effects of maternal supplementation with rumen-protected methionine (RPM), alone or combined with rumen-protected choline (RPC) and betaine (RPB), during the periconceptional and prepartum periods on reproductive outcomes and offspring performance in Chios ewes. One hundred synchronized ewes were assigned to three groups—control (no supplementation), M (5.50 g RPM/day), and MCB (3.50 g RPM, 1.60 g RPC, 0.49 g RPB/day)—from day −14 to +14 relative to mating. Blood was collected on days −14, 0, and +14 for ABTS (2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), ferric-reducing ability (FRAP), and malondialdehyde (MDA), on days 18 and 21 for progesterone, and on day 26 for pregnancy-associated glycoprotein (PAG) detection. Thirty days before and up to lambing, the ewes were further divided into C-C, C-M, C-MCB, M-M, M-C, MCB-MCB, and MCB-C subgroups. Embryonic loss did not differ between groups. FRAP was higher (p < 0.001) in MCB ewes, and ABTS was lower (p < 0.05) in M ewes, in the periconceptional period. Offspring in the C-M, C-MCB, M-M, M-C, and MCB-MCB groups had higher birth weights (p < 0.01), along with increased MDA levels (p < 0.05). The results suggest that maternal methyl donor supplementation during early and/or late gestation enhances antioxidant status, supports embryonic development, and increases birth weight. Full article

Obesity affects approximately 30% of pregnancies worldwide and is one of the leading metabolic disorders among pregnant women. Maternal obesity is often associated with placental dysfunction and structural alterations, which increase the risk of developing complications. Efflux transporters, including P-glycoprotein (P-gp), may impact placental function and fetal development. Consequently, our research examined the effects of obesity on P-glycoprotein expression in both a rat model and human placental tissue. P-gp expression was measured by RT-PCR and Western blot techniques in human and rat placental tissues. Moreover, we further characterized the high-fat and high-sugar diet (HFHSD)-induced gestational obesity rat model by measuring tissue weights. Significant decreases were observed in fetal, placental, and uterus weights in the obese animals near the end of pregnancy. In obese rats, mRNA and protein expression of placental P-gp showed a reduction on gestation days 15, 20, and 22. A similar P-gp reduction was observed in the term placenta in obese women in mRNA and protein levels. We hypothesize that the reduced expression of P-gp may heighten the susceptibility of both the fetus and placenta to P-gp substrates. This alteration could potentially result in an increased risk of pregnancy complications and obesity-related drug contraindications linked to P-gp transport during pregnancy. Full article

Olive cake was incorporated at a low inclusion rate (3.7%) into the rations of dairy cows through partial substitution of maize, and its effects on milk production, general health, and fertility traits were investigated. Multiparous purebred Holstein dairy cows (n = 148) were divided into two groups: a treated group (n = 86) and a control group (n = 62). The control ration (group C) was modified by replacing 1 kg of maize with an equal quantity of olive cake (group T). The experiment lasted from 60 days prepartum to 150 days postpartum. Electronic aids were utilized to quantify daily milk yield and detect estrus expression, while clinical and uterine examinations were performed weekly. Blood samples, uterine epithelial cells, and endometrial tissue samples were collected from a subgroup of healthy animals in both groups at specific time points. Blood samples were examined to determine the β-hydroxybutyric acid (BHBA), acute phase proteins (haptoglobin [Hpt] and serum amyloid A [SAA]), progesterone, and pregnancy-associated glycoproteins concentrations. Uterine epithelial cells were assessed for polymorphonuclear neutrophil (PMN) counts, and the expression of nine genes encoding inflammatory cytokines and immune system activation was analyzed in uterine biopsy tissue. No significant differences (p > 0.05) were observed between groups in milk yield, general morbidity, clinical endometritis, or conception rates. However, animals in group T came to estrus approximately 6 days earlier (p = 0.013) than those in group C; progesterone concentrations on day 7 of the subsequent cycle tended (p = 0.07) to be higher in group T. On day 21, BHBA concentrations were higher in group C than in group T (p < 0.05). Throughout the experiment, Hpt levels in group T were consistently lower (p < 0.001), while SAA was lower on day 7 compared to group C. From days 21 to 42 postpartum, there was a significant reduction in PMN numbers (group C p = 0.02; group T p < 0.0001), with a tendency for a greater reduction rate in group T (p = 0.08). Among the genes studied, a significant difference was revealed in the expression of the ILA1 gene, with strong correlations of gene expression in group C and weak to moderate correlations in group T. In conclusion, under the conditions of this experiment, the inclusion of olive cake into dairy cows’ rations did not affect milk production but improved certain health and fertility parameters, making olive cake a suitable alternative feedstuff for high-producing animals. Full article

The genetic improvement of beef cattle breeds is crucial for the advancement of the beef cattle industry. Whole-genome resequencing technology has been widely applied in genetic breeding as well as research on selection signatures in beef cattle. In this study, 20× whole-genome resequencing was performed on 282 Angus cattle from the Ningxia region, and a high-quality dataset encompassing extensive genomic variations across the entire genome was constructed. The iHS test identified 495 selection signal regions, which included pregnancy-associated glycoprotein (PAG) family genes and immune-related genes such as UL16-binding protein 21 (ULBP21), CD1b molecule (CD1B), and tumor necrosis factor ligand superfamily member 11 (TNFSF11). A quantitative trait locus (QTL) enrichment analysis revealed that several economic traits, including longissimus muscle area, marbling score, carcass weight, average daily gain, and milk yield, were significantly enriched in cattle with these selection signatures. Although the enrichment of QTLs for health traits was low, immune-related genes may indirectly contribute to improvements in production performance. These findings show the genetic basis of economic and adaptive traits in Ningxia Angus cattle, providing a theoretical foundation and guidance for further genetic improvement and breeding strategies. Full article

To the best of our knowledge, no studies in the literature have reported on the relationship between the pregnancy-associated glycoprotein (PAG) concentration and undernutrition during pregnancy in sheep. Therefore, the aim of this study was to investigate the effects of undernutrition on the blood concentration of PAGs in pregnant ewes carrying single and multiple fetuses, undergoing either dietary energy restriction or receiving 100% of their energy requirements during the period of maximal placenta growth. From d 24 to 100 of pregnancy, the ewes were fed ryegrass hay and two different iso-proteic concentrates, fulfilling either 100% of the ewes’ energy requirements (control group; n = 30, 14 singleton pregnancies, 16 multiple pregnancies) or only 50% (feed-restricted group; n = 29; 11 singleton pregnancies, 18 multiple pregnancies). Blood samples were collected from all the ewes the day before intravaginal sponge insertion (T0) and, thereafter, every 30 days starting from d 24 of gestation (T1) until d 30 after parturition (T6), to determine the PAG, progesterone, NEFA, total protein, and glucose concentrations. Our results showed that PAG concentrations are not only influenced by the number of fetuses, but also by the ewe’s diet. In particular, the PAG marginal means were higher in the feed-restricted group than in the control group (7.8 ± 0.6 and 10.8 ± 0.9 ng/mL for the control and feed-restricted groups, respectively; p = 0.040). This finding confirms that a dietary restriction between d 24 and d 100 of gestation leads to a growth in placental functions as inferred from the increase in the concentration of the PAG levels. Therefore, the measurement of PAG concentrations, in addition to serving as a marker of pregnancy, can also serve as a marker of placental functionality. Full article

Pseudopregnancy (PPG) is a common reproductive disorder in dairy goats, characterized by the accumulation of sterile fluid in the uterus and persistence of a corpus luteum, leading to temporary infertility and reduced farm efficiency. This study aimed to determine the pregnancy-associated glycoprotein (PAG) profile in dairy goats and to evaluate the PAG/P4 ratio as a potential novel biomarker for PPG diagnosis. A total of 605 Saanen and crossbreed mated goats were evaluated via transabdominal ultrasonography between 31 and 52 days after the removal of bucks in four intensive dairy farms, presenting an overall PPG incidence of 7.8%. Blood samples from PPG (n = 47), nonpregnant (NPG; negative control; n = 11), and pregnant (PG; positive control; n = 10) does were collected for PAG and P4 analysis. The PAG plasma levels were 0.08 ± 0.02, 0.13 ± 0.04, and 1.45 ± 0.04 OD (optical density) in the PPG, NPG, and PG groups, respectively (p < 0.001). The PAG/P4 ratio was lower in the PPG group (0.01 ± 0.11; p < 0.001) than in the NPG (0.24 ± 0.23) and PG (0.18 ± 0.23) groups. This difference allows for the establishment of a new methodological diagnostic approach to PPG. The area under the curve (AUC) was 0.996 for a cut-off of 0.04 and 97.9% and 100% sensitivity and specificity, respectively. This study suggests that the PAG/P4 ratio can serve as a reliable biomarker for PPG diagnosis, helping to distinguish it from pregnancy and nonpregnancy and improving reproductive management in dairy goats. Full article

Preeclampsia (PE) is a complex and multifaceted obstetric syndrome characterized by several distinct molecular subtypes. It complicates up to 5% of pregnancies and significantly contributes to maternal and newborn morbidity, thereby diminishing the long-term quality of life for affected women. Due to the widespread dissatisfaction with the effectiveness of existing approaches for assessing PE risk, there is a pressing need for ongoing research to identify newer, more accurate predictors. This study aimed to investigate early changes in the maternal serum proteome and associated signaling pathways. The levels of 125 maternal serum proteins at 11–13 weeks of gestation were quantified using liquid chromatography–multiple reaction monitoring mass spectrometry (LC-MRM MS) with the BAK-125 kit. Ten serum proteins emerged as potential early markers for PE: Apolipoprotein M (APOM), Complement C1q subcomponent subunit B (C1QB), Lysozyme (LYZ), Prothrombin (F2), Albumin (ALB), Zinc-alpha-2-glycoprotein (AZGP1), Tenascin-X (TNXB), Alpha-1-antitrypsin (SERPINA1), Attractin (ATRN), and Apolipoprotein A-IV (APOA4). Notably, nine of these proteins have previously been associated with PE in prior research, underscoring the consistency and reliability of our findings. These proteins play key roles in critical molecular processes, including complement and coagulation cascades, platelet activation, and insulin-like growth factor pathways. To improve the early prediction of PE, a highly effective Support Vector Machine (SVM) model was developed, analyzing 19 maternal serum proteins from the first trimester. This model achieved an area under the curve (AUC) of 0.91, with 87% sensitivity and 95% specificity, and a hazard ratio (HR) of 13.5 (4.6–40.8) with p < 0.001. These findings demonstrate that serum protein-based SVM models possess significantly higher predictive power compared to the routine first-trimester screening test, highlighting their superior utility in the early detection and risk stratification of PE. Full article