Effects of foetal size, sex and developmental stage on adaptive transcriptional responses of skeletal muscle to intrauterine growth restriction in pigs.

Intrauterine growth restriction (IUGR) occurs both in humans and domestic species. It has a particularly high incidence in pigs, and is a leading cause of neonatal morbidity and mortality as well as impaired postnatal growth. A key feature of IUGR is impaired muscle development, resulting in decreased meat quality. Understanding the developmental origins of IUGR, particularly at the molecular level, is important for developing effective strategies to mitigate its economic impact on the pig industry and animal welfare. The aim of this study was to characterise transcriptional profiles in the muscle of growth restricted pig foetuses at different gestational days (GD; gestational length ~ 115 days), focusing on selected genes (related to development, tissue injury and metabolism) that were previously identified as dysregulated in muscle of GD90 fetuses. Muscle samples were collected from the lightest foetus (L) and the sex-matched foetus with weight closest to the litter average (AW) from each of 22 Landrace x Large White litters corresponding to GD45 (n = 6), GD60 (n = 8) or GD90 (n = 8), followed by analyses, using RT-PCR and protein immunohistochemistry, of selected gene targets. Expression of the developmental genes, MYOD, RET and ACTN3 were markedly lower, whereas MSTN expression was higher, in the muscle of L relative to AW littermates beginning on GD45. Levels of all tissue injury-associated transcripts analysed (F5, PLG, KNG1, SELL, CCL16) were increased in L muscle on GD60 and, most prominently, on GD90. Among genes involved in metabolic regulation, KLB was expressed at higher levels in L than AW littermates beginning on GD60, whereas both IGFBP1 and AHSG were higher in L littermates on GD90 but only in males. Furthermore, the expression of genes specifically involved in lipid, hexose sugar or iron metabolism increased or, in the case of UCP3, decreased in L littermates on GD60 (UCP3, APOB, ALDOB) or GD90 (PNPLA3, TF), albeit in the case of ALDOB this only involved females. In conclusion, marked dysregulation of genes with critical roles in development in L foetuses can be observed from GD45, whereas for a majority of transcripts associated with tissue injury and metabolism differences between L and AW foetuses were apparent by GD60 or only at GD90, thus identifying different developmental windows for different types of adaptive responses to IUGR in the muscle of porcine foetuses.

Placental and serum levels of human α-Klotho in preeclampsia & intra-uterine growth retardation: A potential sensitive biomarker?

INTRODUCTION: α-Klotho protein has three isoforms: a transmembrane (mKL), a shed- soluble isoform, and a circulating soluble isoform (sKL). mKL is expressed in the kidney and placenta, while sKL is detectable in blood and urine. It is known that α-Klotho levels fluctuate during pregnancy mainly in women with complications such as preeclampsia (PE) and intra-uterine growth restriction (IUGR). METHODS: Forty-nine participants were divided into two groups: healthy and complicated pregnancy (PE, IUGR or both). Tissue samples (2 cm3) from the maternal side, Blood and urine samples were collected during pregnancy and postpartum. Samples were subjected to biochemical (WB), histological (H&E and IHC) staining as well as genetic analysis (qPCR). RESULTS: Blood αKL levels were preserved in both healthy and complicated pregnancies. Significantly lower blood αKL concentrations were found in PE postpartum (PP) compared to levels during pregnancy, and were significantly lower compared with postpartum of a healthy pregnancy. αKL activity was reduced in complicated pregnancies vs. healthy pregnancies. Placen tal mKL levels (ELISA) and expression (WB) were lowered in complicated pregnancies compared with the healthy pregnancies group. Additionally, we found a significant decline in the expression of mKL mRNA in PE/IUGR placentas compared with the healthy group. DISCUSSION: Several studies have focused on the involvement of αKL in normal placentation during pregnancy. Our results suggest lower function of sKL in complicated pregnancy compared with a control, and present differences in placental mKL levels as well as tissue and gene expression between healthy and complicated pregnancy. In light of our results, we conclude that complicated pregnancy is associated with in decline in mKL.

Intrauterine Growth Restriction and Placenta Previa: A Clinical Case Report of an Advanced-Age Pregnancy.

Exploring the intricacies of managing high-risk pregnancies complicated by intrauterine growth restriction (IUGR), placenta previa, and a single umbilical artery requires a comprehensive understanding of their etiologies, mechanisms, and treatment recommendations. This case report delves into the clinical course of a 34-year-old smoker with a pre-pregnancy body mass index of 14.2 kg/m2, shedding light on the considerations posed by a pregnancy in which several risk factors are superimposed on one another. IUGR, affecting 10%-15% of pregnancies, elevated the risk of adverse outcomes during labor and delivery, necessitating careful antenatal monitoring. Placenta previa, with an incidence of 0.3% to 2% in pregnancies, introduced further complications impacting delivery modes and raising the risk of hemorrhage. This report aims to showcase the interconnectedness between these various obstetrical complications and risk factors, to guide maternal-fetal-medicine specialists in making informed decisions during the management of high-risk pregnancies.

When autophagy meets placenta development and pregnancy complications.

Autophagy is a common biological phenomenon in eukaryotes that has evolved and reshaped to maintain cellular homeostasis. Under the pressure of starvation, hypoxia, and immune damage, autophagy provides energy and nutrients to cells, which benefits cell survival. In mammals, autophagy is an early embryonic nutrient supply system involved in early embryonic development, implantation, and pregnancy maintenance. Recent studies have found that autophagy imbalance in placental tissue plays a key role in the occurrence and development of pregnancy complications, such as gestational hypertension, gestational obesity, premature birth, miscarriage, and intrauterine growth restriction. This mini-review summarizes the molecular mechanism of autophagy regulation, the autophagy pathways, and related factors involved in placental tissue and comprehensively describes the role of autophagy in pregnancy complications.

Dataset on neonatal and maternal factors influencing neurodevelopmental outcomes in preterm infants: A study focused on the healthcare context of Mashhad, Iran.

This dataset offers an insight into the neurodevelopmental trajectories of preterm infants, encapsulating a wide array of neonatal and maternal factors. The data variables include demographic details alongside a detailed account of maternal health during pregnancy, encompassing aspects and other complications. Furthermore, the dataset documents neonatal health conditions. It also records critical indicators of neonatal health. The dataset is enriched with data on medical interventions and hospitalization details. It also contains information on the mother's drug usage during pregnancy and sonography results. A significant portion of the dataset is dedicated to the developmental assessment of the infants, utilizing the Bayley Scales to evaluate various domains such as cognitive, language, perceptual, fine motor, and coarse motor skills. The data are categorized to denote normal and abnormal outcomes in these domains, providing a detailed view of the developmental progress of the infants. The reuse potential of this dataset is substantial, serving as a rich resource for researchers and clinicians aiming to delve deeper into the multifaceted influences on preterm infant development. It can significantly contribute to the formulation of early intervention strategies, fostering a better understanding and enhancement of developmental outcomes in preterm infants.

The impact of DNA methylation as a factor of Adverse Pregnancy and Birth Outcomes (APBOs): a systematic review protocol.

BACKGROUND: Deoxyribonucleic acid (DNA) methylation is one of the epigenetic modifications that has gained a lot of interest as a factor influencing fetal programming and as a biomarker for adverse pregnancy and birth outcomes (APBOs). Epidemiological studies have demonstrated that DNA methylation can result in adverse pregnancy and birth outcomes (APBOs) including miscarriage, intrauterine growth restriction (IUGR), low birth weight (LBW), sepsis, and preterm birth (PTB), which may later result in diseases in adulthood. However, the mechanism by which DNA methylation influences these APBOs remains unclear. The systematic review will assess the association between global and gene-specific DNA methylation with adverse pregnancy outcomes. METHOD: The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 checklist will be followed when conducting this systematic review. To develop the search strategy the PI(E)COS (population, intervention/exposure, comparator/control, outcome, and study designs) framework will be followed. Thus far, the research team has retrieved 4721 from Cochrane Library, PubMed, Web of Sciences, and MEDLINE. Out of these, 584 studies have been screened for eligibility, and approximately 124 studies meet the inclusion criteria. Pending the search results identified from the grey literature. For identification of unpublished studies in journals indexed in electronic databases, Google Scholar will be used. I.M and A.S will separately extract data from the articles and screen them, if there are any disagreements between I.M and A.S, then the L.M will resolve them. The methodological quality and bias risk of the included studies will be evaluated using the Critical Appraisal Skill Programme CASP) checklist. [Formula: see text] and [Formula: see text] alpha = 0.10 statistic will be used for assessing statistical heterogeneity between studies. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach will be used to assess and grade the overall quality of extracted data. ETHICS AND DISSEMINATION: Ethical approval is not required. The systematic review will assess available literature on possible associations between DNA methylation with adverse pregnancy and birth outcomes (APBOs) including LBW, IUGR, miscarriage, sepsis, and PTB. The findings could help guide future research assessing DNA methylation and other APBOs. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRCRD42022370647.

Correlation between total deceleration area in CTG records and cord blood pH in pregnancies with IUGR.

PURPOSE: Fetal cardiotocography is the most common method to assess fetal well-being during labor. Nevertheless, its predictive ability for acidemia is limited, both in low-risk and high-risk pregnancies (Nelson et al. in N Engl J Med 334: 613-9, 1996; Rinciples P et al. in Health and Human Development Workshop Report on Electronic Fetal Monitoring : Update on Definitions. no. 2007, 510-515, 2008), especially in high-risk pregnancies, such as those complicated by growth restriction. In this study we aim examine the association between deceleration and acceleration areas and other measure of fetal heart rate in intrapartum fetal monitoring and neonatal arterial cord blood pH in pregnancies complicated by growth restriction. MATERIALS AND METHODS: A retrospective cohort study of 100 deliveries complicated by growth restriction, delivered during 2018, was conducted. Known major fetal anomalies, non-vertex presentation and elective cesarean deliveries were excluded. Total deceleration and acceleration areas were calculated as the sum of the areas within the deceleration and acceleration, respectively. RESULTS: In deliveries complicated by growth restriction, cord blood pH is significantly associated with total deceleration area (p = 0.05) and correlates with cumulative duration of the decelerations (Spearman's rank -0.363, p < 0.05), and total acceleration area (-0.358, p < 0.05). By comparing the cord blood pH in deliveries with a total deceleration area that was above and below the median total deceleration area, we demonstrated a significant difference between the categories. CONCLUSIONS: Cord blood pH significantly correlates with total deceleration area and other fetal monitoring characteristics in neonates with growth restriction. Future studies using real-time, machine-learning based techniques of fetal heart rate monitoring, may provide population specific threshold values that will support bedside clinical decision making and perhaps achieve better outcomes.

Placental assessment using spectral analysis of the envelope of umbilical venous waveforms in sheep.

INTRODUCTION: This study was designed to test the efficacy of an ultrasound flow measurement method to evaluate placental function in a hyperandrogenic sheep model that produces placental morphologic changes and an intrauterine growth restriction (IUGR) phenotype. MATERIALS AND METHODS: Pregnant ewes were assigned randomly between control (n = 12) and testosterone-treatment (T-treated, n = 22) groups. The T-treated group was injected twice weekly intramuscularly (IM) with 100 mg testosterone propionate. Control sheep were injected with corn oil vehicle. Lambs were delivered at 119.5 ± 0.48 days gestation. At the time of delivery of each lamb, flow spectra were generated from one fetal artery and two fetal veins, and the spectral envelopes examined using fast Fourier transform analysis. Base 10 logarithms of the ratio of the amplitudes of the maternal and fetal spectral peaks (LRSP) in the venous power spectrum were compared in the T-treated and control populations. In addition, we calculated the resistive index (RI) for the artery defined as ((peak systole - min diastole)/peak systole). Two-tailed T-tests were used for comparisons. RESULTS: LRSPs, after removal of significant outliers, were -0.158 ± 0.238 for T-treated and 0.057 ± 0.213 for control (p = 0.015) animals. RIs for the T-treated sheep fetuses were 0.506 ± 0.137 and 0.497 ± 0.086 for controls (p = 0.792) DISCUSSION: LRSP analysis distinguishes between T-treated and control sheep, whereas RIs do not. LRSP has the potential to identify compromised pregnancies.

Machine Learning-Based Approach to Predict Intrauterine Growth Restriction.

INTRODUCTION: Creating a prediction model incorporating multiple risk factors for intrauterine growth restriction is vital. The current study employed a machine learning model to predict intrauterine growth restriction. METHODS: This cross-sectional study was carried out in a tertiary hospital in Bandar Abbas, Iran, from January 2020 to January 2022. Women with singleton pregnancies above the gestational age of 24 weeks who gave birth during the study period were included. Exclusion criteria included multiple pregnancies and fetal anomalies. Four statistical learning algorithms were used to build a predictive model: (1) Decision Tree Classification, (2) Random Forest Classification, (3) Deep Learning, and (4) the Gradient Boost Algorithm. The candidate predictors of intrauterine growth restriction for all models were chosen based on expert opinion and prior observational cohorts. To investigate the performance of each algorithm, some parameters, including the area under the receiver operating characteristic curve (AUROC), accuracy, precision, and sensitivity, were assessed. RESULTS: Of 8683 women who gave birth during the study period, 712 were recorded as having intrauterine growth restriction, with a frequency of 8.19%. Comparing the performance parameters of different machine learning algorithms showed that among all four machine learning models, Deep Learning had the greatest performance to predict intrauterine growth restriction with an AUROC of 0.91 (95% confidence interval, 0.85-0.97). The importance of the variables revealed that drug addiction, previous history of intrauterine growth restriction, chronic hypertension, preeclampsia, maternal anemia, and COVID-19 were weighted factors in predicting intrauterine growth restriction. CONCLUSIONS: A machine learning model can be used to predict intrauterine growth restriction. The Deep Learning model is an accurate algorithm for predicting intrauterine growth restriction.

Risk Factors Associated With Intrauterine Growth Restriction: A Case-Control Study.

Background Intrauterine growth restriction (IUGR) is a disorder in which the fetus fails to reach its genetic development potential and is considered to be present when the weight at birth is less than the 10th percentile; as a result, it is at risk of increased postnatal morbidity and mortality. Every year, approximately 24% of newborns worldwide are determined to have IUGR. The objective of the present study was to identify various sociodemographic, medical, and obstetric risk factors associated with IUGR. Methodology A case-control study was conducted from January 2020 to December 2022. Fifty-four cases and 54 controls were included in the study. Postnatal women with neonates having birth weight below the 10th percentile for gestational age (GA) were recruited as cases in the study. Control cases were postnatal women with neonatal birth weight appropriate for (GA). Detailed history with respect to socio-demographic, medical, and obstetric parameters was noted and compared. Results Among the sociodemographic factors, only socioeconomic status showed significant statistical differences with the age group of 21 to 25 years showing maximum (51.9%) IUGR cases. Among the maternal risk factors, anemia (29.6%) and hypertensive disorders of pregnancy (22.2%) were marked as significant risk factors for IUGR. There was no significant difference in the distribution of past medical and obstetric histories between the two research groups. Conclusion Due to the poor living conditions, low literacy rates, and general lack of knowledge, low socioeconomic level increases the risk of IUGR. This leads to nutritional deficiencies and insufficient growth environment which results in anemia and hypertensive disorders of pregnancy which are potent risk factors for IUGR. IUGR may be caused by maternal risk factors as well as past medical and obstetric conditions. However, for the risk factor of IUGR, the birth weight at the time of delivery could be taken into consideration as well.

Maternal neuropeptide galanin levels in pregnancies with intra-uterine growth restriction (IUGR): neurohormonal regulation of fetal weight.

AIM: Galanin is a neuroendocrine peptide with diverse biological actions in humans. Here, we evaluated plasma galanin levels in pregnant women with intrauterine growth restriction (IUGR) to elucidate the mechanism underlying the causal link between regulatory neuropeptides and IUGR. MATERIAL AND METHODS: This prospective case-control study evaluated 40 IUGR pregnancies and 35 healthy body mass index (BMI) and age-matched second and third-trimester pregnant women at Istanbul Teaching and Research Hospital. Serums galanin levels were determined using an enzyme-linked immunosorbent assay (ELISA) kit according to the manufacturer's procedure. RESULTS: Median serum galanin levels were lower in the IUGR group (9.59 pg/ml) than in the control group (12.1 pg/ml), although statically insignificant. Galanin levels were significantly higher in the control group with a BMI ≥ 30 than in those with a BMI < 30; the IUGR group exhibited no significant difference. Galanin levels were higher in the control group premature births than in term pregnancies; the difference was insignificant in the IUGR group. Thus, IUGR minimally impacts circulating maternal galanin levels, indicating that while galanin might affect IUGR pathogenesis, it negligibly contributes to disease progression. CONCLUSION: The lack of correlation between galanin levels and maternal BMI and preterm pregnancies suggests a blunted neuropeptide response to hormonal stimulus in IUGR pregnancies, compared with the positive association with maternal BMI and negative association with healthy preterm pregnancies.

Low Birth Weight Intensifies Changes in Markers of Hepatocarcinogenesis Induced by Fructose Consumption in Rats.

Intrauterine growth restriction (IUGR) due to fetal exposure to glucocorticoid excess results in metabolic inflexibility and hepatic steatosis upon nutritional stress during adulthood. We previously demonstrated that rats born to dexamethasone (DEX)-treated mothers developed hepatic steatosis when exposed to 10% fructose solution during adult life. Persistent triacylglyceride (TAG) accumulation in the liver, in turn, is a feature of non-alcoholic fatty liver disease (NAFLD), which serves as a risk factor for non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). In the present study, we demonstrate that the combination of IUGR and fructose treatment during adulthood also results in increased hepatic myeloperoxidase (MPO) activity, AKT phosphorylation and serum aspartate transaminase. Growth-restricted rats also presented reduced hepatic TRIB3 and GADD45a after fructose treatment. Other markers of cell proliferation, such as Cyclin D, PCNA, Hgf and Hspa4/Hsp70 expression and the number of Ki-67 positive cells, were all increased in the liver of growth- restricted rats treated with fructose. On the other hand, the combination of IUGR and fructose treatment during adult life reduced the levels of IGF-1. In conclusion, our data indicate that after exposure to fructose, adult rats subjected to dexamethasone-induced IUGR display exacerbated molecular changes in markers of NASH and HCC.

Integrative Analysis of Liver Metabolomics and Transcriptomics Reveals Oxidative Stress in Piglets with Intrauterine Growth Restriction.

The correlation between oxidative stress and liver metabolic dysfunction in piglets with intrauterine growth restriction (IUGR) remains limited. Therefore, the objective of the present study was to investigate potential mechanisms of metabolic characteristics induced by oxidative stress in the livers of IUGR piglets using metabolomic and transcriptomic analysis. Analysis of the phenotypic characteristics showed that the liver weight of the intrauterine growth restriction piglets was significantly lower than that of normal birth weight piglets. Intrauterine growth restriction piglets exhibited disordered hepatic cord arrangement and vacuolization as well as excessive lipid accumulation in hepatocytes. In addition, the activities of antioxidant enzymes were significantly decreased in the liver of the intrauterine growth restriction piglets, whereas the level of the lipid peroxidation marker MDA was significantly increased. Finally, our findings revealed that intrauterine growth restriction piglets were involved in a variety of metabolic abnormalities, including mitochondrial dysfunction, imbalance of fatty acid composition, disruption to sources of one-carbon unit supply, and abnormal galactose conversion, which may be responsible for oxidative stress in the liver. In summary, these data provided a detailed theoretical reference for revealing the hepatic metabolic characteristics of intrauterine growth restriction piglets.

Association of Parental Factors and Insulin-like Growth Factor 2 Polymorphism with Intrauterine Growth Restriction.

Polymorphism of insulin-like growth factor 2 (IGF2) is known to play a role in cell development. Only the paternal IGF2 copy is active, while the copy inherited from the mother is inactive. This study aimed to explore whether maternal and paternal factors influence IGF2 polymorphism in newborns with intrauterine growth restriction (IUGR) compared to appropriate for gestational age (AGA). A cross-sectional exploratory study was conducted from June 2014 to November 2015 at the Neonatology, Gynecology 1 Clinic, Cluj-Napoca, Romania. The ApaI IGF2 genotypes and allele frequencies were similar in the IUGR and AGA groups (p-value > 0.10). The IUGR babies with a protective IGF2 genetic profile had significantly younger parents (a difference in the median age of 8 years for mothers and 9 years for fathers; p-value < 0.009). The IUGR babies had parents with lower birth weights than AGA babies (mothers' medians: 2800 g vs. 3100 g; fathers' medians: 3000 g vs. 3400 g; p-value < 0.02). In univariable regression analysis, the mother's and father's birth weight proved to be associated with IUGR. The father's birth weight proved to be the only factor significantly associated with IUGR, independent of the mother's birth weight or the presence of a protective IGF2 genetic profile (odd ratio = 0.998 [0.996 to 1.000], p-value = 0.032).

Gestational cholestasis induced intrauterine growth restriction through triggering IRE1α-mediated apoptosis of placental trophoblast cells.

Epidemiological and animal experimental studies suggest an association between gestational cholestasis and intrauterine growth restriction (IUGR). Here, we explored the mechanism through which gestational cholestasis induced IUGR. To establish gestational cholestasis model, pregnant mice were subcutaneously injected with 17α-Ethynylestradiol (E2) on gestational day 13 (GD13)-GD17. Some pregnant mice were intraperitoneally injected with 4µ8C on GD13-GD17. The results found that the apoptosis of trophoblast cells was elevated in placentas of mice with gestational cholestasis and in deoxycholic acid (DCA)-treated human trophoblast cell lines and primary mouse trophoblast cells. Correspondingly, the levels of placental cleaved caspase-3 and Bax were increased, while placental Bcl2 level was decreased in mice with gestational cholestasis and in DCA-treated trophoblast cells. Further analysis found that placental IRE1α pathway was activated in mice with gestational cholestasis and in DCA-treated trophoblast cells. Interestingly, 4µ8C, an IRE1α RNase inhibitor, significantly inhibited caspase-3 activity and apoptosis of trophoblast cells in vivo and in vitro. Importantly, 4µ8C rescued gestational cholestasis-induced placental insufficiency and IUGR. Furthermore, a case-control study demonstrated that placental IRE1α and caspase-3 pathways were activated in cholestasis cases. Our results provide evidence that gestational cholestasis induces placental insufficiency and IUGR may be via triggering IRE1α-mediated apoptosis of placental trophoblast cells.

Leptin Levels of the Perinatal Period Shape Offspring's Weight Trajectories through the First Year of Age.

Background: Leptin is a hormone regulating lifetime energy homeostasis and metabolism and its concentration is important starting from prenatal life. We aimed to investigate the association of perinatal leptin concentrations with growth trajectories during the first year of life. Methods: Prospective, longitudinal study, measuring leptin concentration in maternal plasma before delivery, cord blood (CB), and mature breast milk and correlating their impact on neonate's bodyweight from birth to 1 year of age, in 16 full-term (FT), 16 preterm (PT), and 13 intrauterine growth-restricted (IUGR) neonates. Results: Maternal leptin concentrations were highest in the PT group, followed by IUGR and FT, with no statistical differences among groups (p = 0.213). CB leptin concentrations were significantly higher in FT compared with PT and IUGR neonates (PT vs. FT; IUGR vs. FT: p < 0.001). Maternal milk leptin concentrations were low, with no difference among groups. Maternal leptin and milk concentrations were negatively associated with all the neonates' weight changes (p = 0.017 and p = 0.006), while the association with CB leptin was not significant (p = 0.051). Considering each subgroup individually, statistical analysis confirmed the previous results in PT and IUGR infants, with the highest value in the PT subgroup. In addition, this group's results negatively correlated with CB leptin (p = 0.026) and showed the largest % weight increase. Conclusions: Leptin might play a role in neonatal growth trajectories, characterized by an inverse correlation with maternal plasma and milk. PT infants showed the highest correlation with hormone levels, regardless of source, seeming the most affected group by leptin guidance. Low leptin levels appeared to contribute to critical neonates' ability to recover a correct body weight at 1 year. An eventual non-physiological "catch-up growth" should be monitored, and leptin perinatal levels may be an indicative tool. Further investigations are needed to strengthen the results.

Associations between testicular development and fetal size in the pig.

BACKGROUND: Impaired reproductive performance is the largest contributing factor for the removal of boars from commercial systems. Intrauterine growth restricted piglets represent 25% of the total number of piglets born and have impaired reproductive performance. This study aimed to improve the understanding of temporal changes in testicular gene expression during testes development in fetuses of different size. The lightest and closest to mean litter weight (CTMLW) male Large White × Landrace littermates were collected at gestational days (GD) 45, 60 and 90 (n = 5-6 litters/GD). RESULTS: Testes weight and testes weight as a percentage of fetal weight were not associated with fetal size at GD60 or 90. Fetal plasma testosterone was not associated with fetal size at GD90. There was no association between fetal size and seminiferous tubule area and number, number of germ or Sertoli cells per tubule. The lightest fetuses tended to have wider seminiferous tubules compared to the CTMLW fetuses at GD90 (P = 0.077). The testicular expression of KI67 (P ≤ 0.01) and BAX:BCL2 ratio (P = 0.058) mRNAs decreased as gestation progressed. Greater SPP1 mRNA expression was observed at GD60 when compared with GD45 and 90 (P ≤ 0.05). Lower expression of DMRT1 and SPP1 (P < 0.01) mRNAs was observed in testes associated with the lightest fetuses compared to the CTMLW fetuses at GD90. CONCLUSIONS: These findings provide novel insights into the expression profiles of genes associated with testicular development and function. Further, these data suggest that programming of reproductive potential in IUGR boars occurs late in gestation, providing a platform for further mechanistic investigation.

Ischemia modified albumin levels in intrauterine growth restriction: levels are increased in fetal cord blood but not in maternal blood.

OBJECTIVES: In this study, our aim was to determine the differences between intrauterine growth restriction (IUGR) and normal birth weight fetuses in terms of ischemia modified albumin (IMA) levels. For this purpose, we measured ischemia modified albumin levels in the cord blood of fetuses and venous blood of mothers. MATERIAL AND METHODS: This study is a prospective study conducted at University of Health Sciences Tepecik Training and Research Hospital between January 2018 and December 2019. According to the inclusion/exclusion criteria, 227 patients were included in the study. Participants were divided into two groups according to the presence (patient group) or absence (control group) of intrauterine growth restriction (IUGR). In addition to routine parameters recorded during pregnancy, the IMA levels and Doppler USG findings of all participants were recorded. RESULTS: The mean cord blood serum IMA levels of the patient group were significantly elevated compared to controls (p = 0.038). Whereas mean maternal blood serum IMA levels were similar among groups (p = 0.453). The cord blood and mother blood serum IMA levels were not significantly different with regard to the presence or absence of perinatal asphyxia. CONCLUSIONS: In the literature, studies evaluating IMA levels in the cord and maternal blood of IUGR fetuses are limited. In IUGR patients, IMA level is expected to increase and in our study, IMA levels were significantly increased but the presence of oxidative stress has not been found to affect IMA levels.

The dynamical interplay of perinatal leptin with birthweight and 3-month weight, in full-term, preterm, IUGR mother-infant dyads.

OBJECTIVE: To evaluate the dynamical interplay between perinatal leptin concentrations and neonatal weight evolution until 3 months of age. METHODS: In a prospective observational study, maternal, cord blood and neonatal plasma leptin concentrations were correlated to birthweight and 3-month weight in 26 full-term, 20 preterm, and 17 intrauterine growth restriction (IUGR) mother-neonate couples. RESULTS: The median of maternal, cord blood, neonatal leptin concentrations were significantly different among the three groups (p = 0.010; <0.001; =0.041 correspondingly). In the respect of the full-term group, higher concentrations were reported in preterm and IUGR mothers and lower concentrations in cord blood and neonatal plasma. The post-hoc comparisons showed that maternal concentrations were significantly higher in the IUGR group (p = 0.005 vs full-term), cord blood concentrations resulted always significantly lower (preterm, IUGR vs full-term p < 0.001) and neonatal concentrations were significantly lower in the preterm group (p = 0.018 vs full-term). Neonatal birthweight and 3-month weight were always significantly different among groups (p < 0.001), even if preterm and IUGR still had lower weight than full-term, the percent increasing of weight between birth and 3-month demonstrated that preterm and IUGR infants have grown significantly faster, (preterm, IUGR vs full-term p < 0.001). The univariable analysis showed a maternal leptin association with offspring' birthweight (R = -38%, p = 0.006) and with 3-month weight (R = -43%, p = 0.002). Accounting for confounders, these associations lost significance. Cord blood leptin concentrations positively correlated with birthweight and with 3-month weight (both, p < 0.001). The latter correlation, when adjusting for birthweight became negative (R = -43% p < 0.001). CONCLUSION: Our results showed that maternal leptin levels lost their influence on neonatal weight when considering confounders. At 3-month, once birthweight adjusted, the percent increasing of weight was statistically larger in preterm and IUGR than the full-term group and the correlation between cord blood leptin and weight turned negative, from positive at birth. These data may be a clue for further investigation on the relationship between perinatal leptin concentrations and catch-up growth.

Changes in Circulating Kisspeptin Levels During Each Trimester in Women With Antenatal Complications.

CONTEXT: Antenatal complications such as hypertensive disorders of pregnancy (HDP), fetal growth restriction (FGR), gestational diabetes (GDM), and preterm birth (PTB) are associated with placental dysfunction. Kisspeptin has emerged as a putative marker of placental function, but limited data exist describing circulating kisspeptin levels across all 3 trimesters in women with antenatal complications. OBJECTIVE: We aimed to assess whether kisspeptin levels are altered in women with antenatal complications. METHODS: Women with antenatal complications (n = 105) and those with uncomplicated pregnancies (n = 265) underwent serial ultrasound scans and blood sampling at the Early Pregnancy Assessment Unit at Hammersmith Hospital, UK, at least once during each trimester (March 2014 to March 2017). The women with antenatal complications (HDP [n = 32], FGR [n = 17], GDM [n = 35], PTB [n = 11], and multiple complications [n=10]) provided 373 blood samples and the controls provided 930 samples. Differences in circulating kisspeptin levels were assessed. RESULTS: Third-trimester kisspeptin levels were higher than controls in HDP but lower in FGR. The odds of HDP adjusted for gestational age, maternal age, ethnicity, BMI, smoking, and parity were increased by 30% (95% CI, 16%-47%; P < 0.0001), and of FGR were reduced by 28% (95% CI, 4-46%; P = 0.025), for every 1 nmol/L increase in plasma kisspeptin. Multiple of gestation-specific median values of kisspeptin were higher in pregnancies affected by PTB (P = 0.014) and lower in those with GDM (P = 0.020), but not significantly on multivariable analysis. CONCLUSION: We delineate changes in circulating kisspeptin levels at different trimesters and evaluate the potential of kisspeptin as a biomarker for antenatal complications.