Fetal Growth Restriction Research Articles

Association between Subclinical Hypothyroidism and Adverse Pregnancy Outcomes in Assisted Reproduction Technology Singleton Pregnancies: A Retrospective Study.

Background/Objectives: Women with subclinical hypothyroidism (SCH) were reported to be at an increased perinatal risk. We aimed to investigate the relationship between SCH and perinatal outcomes in singleton pregnancies resulting from assisted reproduction technology (ART). Methods: We retrospectively examined the perinatal outcomes of ART singleton pregnancies in women who underwent thyroid function screening before conception and delivered at our hospital from January 2020 to July 2023. We defined SCH as thyroid-stimulating hormone (TSH) levels > 2.5 mU/L and normal free T4 levels. The patients were categorized into three groups: normal thyroid function (group A), SCH without levothyroxine therapy (group B), and SCH with levothyroxine therapy (group C). The risks of preterm birth, preeclampsia, fetal growth restriction, manual placental removal, and blood loss at delivery were compared among the three groups. Results: Out of the 650 ART singleton deliveries, 581 were assigned to group A, 34 to group B, and 35 to group C. The preterm birth rate at <34 weeks was significantly higher in group B and significantly lower in group C than in group A. The rate of preterm delivery at <34 weeks increased in correlation with TSH levels. Levothyroxine therapy was the significant preventive factor for preterm birth at <34 weeks. Conclusions: The preterm birth rate before 34 weeks was significantly higher in the SCH group. Levothyroxine therapy is a significant protective factor against preterm birth before 34 weeks. Universal screening for thyroid function and appropriate hormone therapy in pregnant women may help reduce perinatal risks, including preterm birth.

Comprehensive evaluation of fetal renal ultrasound parameters for fetal growth restriction

ObjectiveThis study aims to investigate variances in renal ultrasound parameters between fetuses experiencing fetal growth restriction (FGR) and those with normal intrauterine development, with the intent to offer actionable insights for clinical management. MethodForty-five pregnant women diagnosed with FGR between 28 and 36 weeks of gestation, who underwent examination at Wenzhou People's Hospital from September 2021 to June 2023, constituted the FGR group. Concurrently, 65 pregnant women with normal intrauterine development at matching gestational weeks formed the control group. Renal ultrasound parameters, encompassing renal artery peak systolic velocity (PSV), end diastolic velocity (EDV), time averaged maximum velocity (TAMX), resistive indices (S/D, PI, RI), ratios of renal volume to gestational age (RV/WEEK) and estimated fetal weight (RV/EFW), vascular indices (VI, FI, VFI), were compared between the two groups. All parameters represented the mean values of bilateral kidneys. ResultIn the FGR group, fetal renal artery PSV (37.71 ± 9.93 cm/s), EDV (6.19 ± 1.50 cm/s), TAMX (15.10 ± 3.83 cm/s), RV/WEEK (0.45 ± 0.12), RV/EFW (7.53 ± 3.24), VI (22.19 ± 15.00), and VFI (5.53 ± 3.63) were significantly lower compared to the control group (PSV: 47.11 ± 11.24 cm/s, EDV: 7.13 ± 2.00 cm/s, TAMX: 17.85 ± 3.85 cm/s, RV/WEEK: 0.66 ± 0.19, RV/EFW:9.20 ± 3.17, VI: 28.67 ± 14.72, VFI: 7.40 ± 3.68). Conversely, fetal renal artery resistive indices (S/D: 9.09 ± 2.58, PI: 2.71 ± 0.56, RI: 0.92 ± 0.04) in the FGR group were notably higher than those in the control group (S/D: 6.22 ± 1.93, PI: 2.20 ± 0.73, RI: 0.87 ± 0.04), with statistical significance (P < 0.05). No significant difference was found in renal FI between the FGR group (26.78 ± 6.59) and the control group (26.89 ± 5.82) (P > 0.05). Receiver operating characteristic (ROC) curve analysis revealed higher diagnostic efficacy for RV/WEEK and RI among individual indicators, while combined parameter application yielded the highest diagnostic efficiency. ConclusionUtilizing a comprehensive evaluation of fetal kidney ultrasound parameters with multiple indices facilitates early screening and diagnosis of FGR fetuses, thereby aiding clinical decision-making and enhancing newborn birth outcomes.

Fetal epicardial fat thickness and modified myocardial performance index in late-onset fetal growth restriction.

In our study, we aimed to investigate the value of fetal epicardial fat thickness (EFT) and modified myocardial performance index (mod-MPI) in fetal growth restriction (FGR) that develops after the 32nd week of gestation. Fifty-six pregnant women who met the inclusion and exclusion criteria were included in the study and were divided into two groups: pregnancies diagnosed with FGR after the 32nd week of gestation (FGR group) and those without (control group). Demographic and obstetric histories, ultrasonographic and clinical characteristics, fetal EFT and mod-MPI values, and neonatal outcomes of the groups were recorded, and comparisons were made between the groups. Additionally, the diagnostic performance of fetal EFT value in late FGR was investigated. The FGR group had fetal EFT that was statistically significantly lower (1.11 ± 0.21 vs. 1.34 ± 0.23, p = 0.001). The FGR group had a significantly lower isovolumetric contraction time (ICT) (31.04 ± 6.88 vs. 35.14 ± 7.58, p = 0.048). The two groups' isovolumetric relaxation time (IRT), ejection time (ET), and mod-MPI values (p values 0.871, 0.55, and 0.750, respectively) were comparable. Receiver operating characteristic (ROC) analysis at a cutoff of 1.2 revealed 76.1% sensitivity and 74.2% specificity, respectively, for the diagnostic performance of the fetal EFT value in late-onset FGR. There was a positive predictive value (PPV) and negative predictive value (NPV) of 64.0% and 83.8%, respectively. We found that fetal EFT was significantly lower in FGR and may be useful in diagnosing FGR. However, we observed that mode-MPI did not change in FGR.

Umbilical Artery Doppler and Adverse Outcomes in Severe Preeclampsia Without Fetal Growth Restriction: A Retrospective Cohort Study.

Background and objective Severe preeclampsia may be managed expectantly before 34 weeks gestation with close surveillance.Utilized in fetal growth restriction (FGR), evidence supports umbilical artery (UA) Dopplerpreventing neonatal morbidity from hypertensive disease and predicting adverse outcomes in preeclampsia. We evaluated the association of abnormal UA Doppler waveforms with early delivery (before 34 weeks gestation) and adverse maternal-fetal outcomes in patients with early severe preeclampsia without FGR. Methodology This is a retrospective cohort study of singleton pregnancies with International Classification of Diseases (ICD) Ninth or Tenth Revision, defined severe preeclampsia diagnosed before 34 weeks gestation without FGR from January 1, 2018, through January 27, 2023, at a large tertiary care center where S/D ratios were calculated from UA Doppler interrogation of a free loop of cord at least once weekly. This study was approved by the IRB (ID:00002216) and granted a full Health Insurance Portability and Accountability Act (HIPAA) waiver of consent. Exclusion criteria were major congenital anomalies, congenital infection, aneuploidy, leaving against medical advice >24 hours, and patient instability on admission defined as condition(s) precluding expectant management by the American College of Obstetrics and Gynecology. The primary outcome was delivery before 34 weeks gestation. Secondary outcomes were the mode of delivery and maternal/fetal complications. Patient characteristics and outcomes for normal versus abnormal UA Doppler groups were compared with chi-square, t-tests, and Fisher's exact test. Odds ratios and relative risks were calculated to compare outcomes. Results Of 194 patients with severe preeclampsia, 107 met inclusion criteria. Thirty-four patients had abnormal UA Doppler studies. There were no differences in demographic and clinical data between patients with normal and abnormal UA Doppler studies. Patients with abnormal UA Doppler studies were more likely to deliver before 34 weeks (OR=3.91; 95%CI 1.24-12.33) for worsening severe features (OR=3.85; 95% CI 1.42-10.41), and were less likely to deliver vaginally (OR=0.12; 95% CI 0.03-0.54). Abnormal UA Doppler studies were associatedwith an increased risk of neonatal complications (OR=6.46; 95% CI 1.42-29.42) and respiratory distress syndrome (RDS) (OR=4.75; 95%CI 1.32-17.16). Abnormal UA Doppler subgroups were divided into patients with elevated S/D >95% Acharya (N=22) and absent end-diastolic flow (EDF) (N=10). The elevated S/D group tended to deliver before 34 weeks gestation for worsening severe features (OR=3.71, 95% CI 1.144-12.050) and had a higher risk of neonatal complications (RR 1.404; 95% CI 1.213-1.624). The absent EDF subgroup was more likely to deliver before 34 weeks (RR=1.52; 95%CI 1.29-1.79) for abnormal fetal testing (OR=6.92; 95%CI 1.71-28.08) and undergo primary cesarean delivery (OR=7.23; 95%CI 1.43-36.61). Conclusion Pregnancies with severe preeclampsia without FGR displayed a high incidence of abnormal UA Doppler waveforms associated with loss of clinical stability and adverse fetal outcomes. The groups with more impedance to umbilical artery flow tended to deliver earlier, and as the Doppler shifted from elevated S/D to absent end-diastolic flow, the mode of delivery shifted to cesarean delivery with increased risk of abnormal fetal testing. These results support the utility of UA Doppler surveillance in severe preeclampsia.

First reported case of Acute Disseminated Encephalomyelitis in pregnancy in Sri Lanka

Acute Disseminated Encephalomyelitis (ADEM) complicating pregnancy is a rare occurrence, posing challenges to the management due to maternal and fetal risks including fetal loss, fetal anomalies, intrauterine fetal growth restriction (FGR) and preterm labour. We report a case of a 21-year-old primiparous woman who was diagnosed with ADEM during the second trimester. She was treated with high dose intravenous (IV) steroids as well as IV immunoglobulin. She made complete neurological recovery within two months, but there were fetal complications including oligohydramnios, intrauterine growth restriction and low birth weight. The baby was delivered via elective caesarean section due to suspicious cardiotocograph and abnormal fetal doppler studies indicative of compromised fetal circulation. The baby was given special baby care unit (SBCU) care. However, both the mother and baby were safely discharged following six days of special neonatal care. This is the first reported case of ADEM in pregnancy in Sri Lanka, and highlights the challenges in management.

The effect of antenatal corticosteroid administration on umbilical artery Doppler velocimetry in pregnancies complicated with fetal growth restriction

Objective: To examine the effect of antenatal corticosteroid administration on umbilical artery (UA) Doppler measurements in pregnancies complicated with fetal growth restriction (FGR). Methods: This cross-sectional study was conducted with 149 pregnant women scheduled for antenatal corticosteroid therapy because of the possibility of preterm birth. UA Doppler measurements (PI, S/D ratio, RI) before antenatal corticosteroid administration and 24 and 48 hours after the last dose of corticosteroid administration were evaluated and compared with each other in pregnant groups complicated with FGR and uncomplicated with FGR. Results: No statistically significant change was observed in UA Doppler parameters 24 and 48 hours after antenatal corticosteroid treatment in each group with and without FGR. While there was no significant difference between the precorticosteroid UA Doppler parameters (PI, S/D ratio, RI) of the two groups with and without FGR, the values of these parameters 24 hours after the last dose of treatment were statistically higher in the group complicated with FGR than in the uncomplicated group. However, no statistical difference was observed in UA Doppler parameters between the two groups 48 hours after the last dose of treatment. Conclusion: Antenatal corticosteroid does not permanently affect UA Doppler parameters in the case of FGR. Close monitoring of the fetus for 72 hours after the first dose of antenatal corticosteroid may be helpful in pregnant women complicated by FGR.

Polymorphisms in myeloperoxidase and tissue inhibitor of metalloproteinase-1 genes and their association with preeclampsia in the Chinese Han population

Hypertensive disorders of pregnancy (HDP) are multifaceted syndromes unique to pregnancy, characterized by increased blood pressure, edema, and proteinuria. Patients with HDP exhibit signs of endothelial dysfunction, possibly linked to increased myeloperoxidase (MPO) level and aberrant oxidative stress. Additionally, altered level of tissue inhibitor of metalloproteinase-1 (TIMP1) protein is associated with placental ischemia, hypoxia, and maternal vascular endothelial damage. Preeclampsia (PE) represents a critical stage of HDP that poses severe threats to maternal and fetal safety. This study aimed to determine the relationship between MPO and TIMP1 polymorphisms and the risk of PE in the Chinese Han population. Single nucleotide polymorphisms (SNPs), including MPO rs7208693, MPO rs2243828, and TIMP1 rs6609533, were genotyped in 170 patients with PE and 303 control participants. No significant association was observed between MPO polymorphisms (rs7208693 and rs2243828) and the risk of PE, whereas significant association between the TIMP1 rs6609533 A > G SNP and PE susceptibility was found. Specifically, individuals with the GG or AG genotypes had elevated risk of PE compared to those harboring the AA genotype. Furthermore, in the PE group, patients carrying the G allele were more likely to experience fetal growth restriction (FGR). In the non-PE group, the association between the G allele and the risk of FGR was not evident. In conclusion, the TIMP1 rs6609533 G allele in Chinese Han women was identified as a risk factor for PE. Our results indicated that the TIMP1 rs6609533 SNP can serve as a biomarker for the clinical diagnosis and treatment of PE.

Dietary factors and risk for adverse pregnancy outcome: A Mendelian randomization analysis.

This study aims to explore the link between dietary habits and adverse pregnancy outcomes (APOs), including preterm birth (PB), preeclampsia (PE), gestational diabetes mellitus (GDM), fetal growth restriction (FGR), and spontaneous abortion (SA) through two-sample Mendelian randomization (MR). We accessed publicly available genome-wide association studies' (GWAS) summary statistics for dietary habits and APOs, respectively. We used five MR methods to synthesize MR estimates across genetic instruments. To ensure the robustness of our results, we assessed heterogeneity, and horizontal pleiotropy, and conducted sensitivity analyses. The primary analysis showed that intake of dried fruit (odds ratio (OR), 0.522; 95% confidence interval (CI): 0.291-0.935) and fresh fruit (OR, 0.487; 95% CI: 0.247-0.960) was related to a decreased risk of PB. While intake of tea (OR, 1.602; 95% CI: 1.069-2.403) and poultry (OR, 6.314; 95% CI: 1.266-31.488) was linked to a heightened risk of PB. Cheese intake was a protective factor against PE (OR, 0.557; 95% CI: 0.337-0.920) and GDM (OR, 0.391; 95% CI: 0.270-0.565). Intake of lamb/mutton had a negative relationship with PE (OR, 0.372; 95%CI: 0.145-0.954), whereas oily fish consumption showed a positive relationship with FGR (OR, 2.005; 95% CI: 1.205-3.339). However, after correction using the false discovery rate (FDR) analysis, only the intake of cheese showed a significant causal relationship with GDM (p < .001). Our study preliminarily found that cheese intake was significantly associated with the lower risk of GDM, while others were suggestively associated with the risk of APOs. Well-designed prospective studies are still needed to confirm our findings in the future.

Coxsackievirus Group B Infections during Pregnancy: An Updated Literature Review.

Coxsackievirus group B (CVB), a member of the Picornaviridae family and enterovirus genus, poses risks during pregnancy due to its potential to cause severe fetal and neonatal infections. Transmission primarily occurs through fecal-oral routes, with infections peaking mostly in warmer months. Vertical transmission to the fetus can lead to conditions such as myocarditis, encephalitis, and systemic neonatal disease, presenting clinically as severe myocardial syndromes and neurological deficits. Diagnostic challenges include detecting asymptomatic maternal infections and conducting in utero assessments using advanced techniques like RT-PCR from amniotic fluid samples. Morbidity and mortality associated with congenital CVB infections are notable, linked to preterm delivery, fetal growth restriction, and potential long-term health impacts such as type 1 diabetes mellitus and structural cardiac anomalies. Current treatments are limited to supportive care, with emerging therapies showing promise but requiring further study for efficacy in utero. Preventive measures focus on infection control and hygiene to mitigate transmission risks, which are crucial especially during pregnancy. Future research should aim to fill knowledge gaps in epidemiology, improve diagnostic capabilities, and develop targeted interventions to enhance maternal and fetal outcomes.

Prevalence of placental bed spiral artery pathology in preeclampsia and fetal growth restriction: A prospective cohort study

BackgroundPreeclampsia and fetal growth restriction (PE/FGR) are pregnancy complications known to be associated with poor utero-placental function due to abnormal “physiological” remodeling of spiral arteries and unfavorable maternal cardiovascular health. However, the prevalence and degree of impaired spiral artery remodeling has not been clearly established. MethodProspective, multi-center observational cohort study to assess the prevalence of lesions associated with abnormal development of spiral arteries in placental bed biopsies systematically obtained from 121 women undergoing Caesarian section for PE/FGR compared with a reference group of 149 healthy controls. ResultsPE/FGR was associated with a high prevalence of impaired spiral artery remodeling compared with controls (63.6 vs 10.1 %, p < 0.001), and a higher prevalence of non-remodeled spiral arteries without the presence of intramural trophoblast (45.5 vs 6.7 %, p < 0.001), despite abundant interstitial trophoblast invasion in surrounding decidua and myometrium. Normal remodeling was associated with circumferential presence of intramural trophoblast and hardly any trophoblast in surrounding tissue. Acute atherosis (28.9 vs 3.4 %, p < 0.001) and thrombosis (16.5 vs 5.4 %, p = 0.003) lesions were significantly more prevalent in PE/FGR. Impaired remodeling, acute atherosis and thrombosis lesions were equally present in both decidual and myometrial segments of the spiral arteries in both groups. Impaired remodeling was most prominent in the groups with FGR (with or without PE) and thrombosis was most often seen in the group with PE and FGR. ConclusionPE/FGR is associated with a high prevalence of impaired physiological remodeling and vascular lesions of the uterine spiral arteries in the placental bed.

FERN: is it possible to conduct a randomised controlled trial of intervention or expectant management for early-onset selective fetal growth restriction in monochorionic twin pregnancy – protocol for a prospective multicentre mixed-methods feasibility study

IntroductionSelective fetal growth restriction (sFGR) in monochorionic twin pregnancy, defined as an estimated fetal weight (EFW) of one twin <10th centile and EFW discordance ≥25%, is associated with stillbirth and...

Does threatened miscarriage have an influence on maternal &amp; fetal outcomes during pregnancy? - Our experience in Kozhikode, North Kerala

: Bleeding in early pregnancy is a threat to developing embryo and constitute a significant source of anxiety to both parents, obstetrician. Adverse outcomes included miscarriage, placenta previa, abruption, preeclampsia, caesarean section, preterm labor, and preterm premature rupture of membranes, fetal growth restriction, and low birth weight.: The aim of this study was to find the association between threatened miscarriage and adverse pregnancy outcomes in both mother and fetus. Objective was to compare the pregnancy outcomes in normal patients (controls) and in those with threatened miscarriage (cases).: A 1year prospective study was conducted in Kozhikode; Kerala. The study included 140 antenatal patients who were grouped into 70 cases and 70 controls.: P-value is less than the significance level 0.05. It was found that caesarean section was significantly higher in case (66.2%) than control (42.9%). Pre-term delivery was also found to be higher in case (60.3%) compared to control (15.7%). PPROM was significantly higher in case (11.4%) compared to control (2.9%). Low birth weight was also higher in case (16.2%) than control (1.4%). : There was significant association between threatened miscarriage and outcomes like Preterm Labor, preterm premature rupture of membranes, caesarean section, fetal growth restriction, and low birth weight. There was no significant association between threatened miscarriage and outcomes like miscarriage, placenta previa, placental abruption, preeclampsia.

Doppler abnormalities and perinatal outcome in growth restricted fetuses in a tertiary care center: A retrospective study

Intrauterine Growth Restriction (IUGR), is a significant contributor to foetal and neonatal morbidity and mortality. The majority of prenatal problems that result in negative outcomes can be avoided with early identification and prompt management measures. Doppler ultrasonography is widely used to make the diagnosis of IUGR in foetuses and to monitor the progression in-utero. The purpose of the current study is to predict the perinatal prognosis of foetuses with growth restriction based on doppler abnormalities. A retrospective analysis was conducted among 134 cases of diagnosed IUGR in routine ultrasound from the year 2015 to 2021. Socio-demographic data, baby delivery details, and the ultrasound details regarding doppler evaluation of Umbilical Artery (UA) and Middle cerebral artery (MCA) were collected. The fetal cerebro-placental ratio (CPR) was then analysed with the fetal outcomes in the cases. Abnormal doppler was found in 31 out of 134 cases, with a CPR&amp;#60;1. There was significant association of gestational age, mode of delivery and birth weight variables with abnormal doppler. The mean birth weight of the baby (2052 grams), and NICU admission of the babies (17.6%) have also shown statistical association with abnormal doppler (p&amp;#60;0.05).Doppler velocimetry is the non-invasive method for identifying foetal growth restriction and anticipating perinatal difficulties, which aids the obstetrician in providing good antenatal care and prompt intervention and prevention of perinatal morbidity and mortality.

A New Look at Immunogenetics of Pregnancy: Maternal Major Histocompatibility Complex Class I Educates Uterine Natural Killer Cells.

Our incomplete knowledge of maternal-fetal interface (MFI) physiology impedes a better understanding of the pathological mechanisms leading to pregnancy complications, such as pre-eclampsia and fetal growth restriction. At the MFI, uterine natural killer (uNK) cells do not attack fetal cells but engage in crosstalk with both fetal and maternal cells to support feto-placental development. However, mother and fetus are genetically half-mismatched and certain combinations of variable immune genes-human leukocyte antigens (HLAs) and killer-cell immunoglobulin-like receptor (KIR), indeed, the most variable gene sets in the genome-associate with pregnancy outcomes, suggesting that these interactions regulate uNK cell function. How do these interactions influence the physiology and pathology at the MFI? Uterine NK cell function is regulated by both maternal and fetal Major Histocompatibility Complex (MHC); however, evidence for fetal cells educating uNK cells is lacking, and new evidence shows that maternal rather than fetal MHC class I molecules educate uNK cells. Furthermore, uNK cell education works through self-recognition by the ancient and conserved NKG2A receptor. Pregnant mice lacking this receptor produce normal litter sizes, but a significant portion of the offspring have low birthweight and abnormal brain development. Evidence from a genome-wide association study of over 150,000 human pregnancies validates the finding because women whose NKG2A receptor is genetically determined to engage their own MHC class I molecules are exposed to lower risk of developing pre-eclampsia, suggesting that maternal uNK cell education is a pre-requisite for a healthy pregnancy and, likely, for healthy offspring too.

Impacts of tolylfluanid on implantation and placental development: Disruption of mitochondrial function and implantation-related gene expression in vitro and in vivo

Tolylfluanid is a widely used pesticide and antifouling agent in agricultural and marine industries and is recognized as a potential endocrine disruptor. However, the toxicological effects of tolylfluanid on the placenta development was not elucidated. This study used trophoblastic cell (HTR-8/SVneo cell) and endometrial cell (T HESCs) lines as in vitro model and mouse models as in vivo model to investigate the toxic effects of tolylfluanid on implantation-associated cell and placenta development during early pregnancy. Experimental results indicated that both cell lines exhibited reduced viability upon tolylfluanid exposure. Various in vitro experiments were conducted at <1 mg/L concentration. The results indicate that tolylfluanid can arrest cell cycle and induce apoptosis in endometrial and trophoblastic cells, abnormally regulate Ca2+ homeostasis and MAPK signaling pathways, and disrupt mitochondrial function. In vivo experiments, subchronic tolylfluanid exposure to mouse during puberty and pregnancy period impaired placenta development, resulting in reduced fetal and placental weight, abnormal placental structures, and altered gene expression. Specifically, a decrease in the ratio of labyrinth/junctional zones and changes in placenta gene expression patterns after tolylfluanid exposure were similar to characters of adverse pregnancy outcomes such as preeclampsia and fetal growth restriction (FGR). This study suggests that tolylfluanid exposure may have negative outcomes on female reproduction, and highlights the need for stricter regulation and monitoring of tolylfluanid use to protect women's reproductive health. This is the first study indicating the adverse effects of tolylfluanid on implantation and placental development during pregnancy.

Development and validation of a prognostic model to predict birth weight: individual participant data meta-analysis

ObjectiveTo predict birth weight at various potential gestational ages of delivery based on data routinely available at the first antenatal visit.DesignIndividual participant data meta-analysis.Data sourcesIndividual participant data of four cohorts...

Evaluation of the effect of vitamin D on the placenta, kidney, and growth of developing fetuses in preeclamptic mice

Background Preeclampsia (PE) is a complicated syndrome that leads to maternal and fetal morbidity and mortality. PE is defined by the elevation of the mother’s blood pressure (hypertension) and the presence of proteinuria. Objective This study aimed to evaluate the effect of vitamin D on 18-day-old mice fetuses in which the PE syndrome was induced in the mother by L-NG-nitro arginine methyl ester (L-NAME). Materials and methods The mice grouping was divided as: (a) the control group (group I), (b) the female pregnant mice of the second group intraperitoneally injected with 50 mg/kg/day of L-NAME (group II), (c) the female pregnant mice of the third group were administered orally with 50 IU/kg/day of vitamin D (group III), and (d) the female pregnant mice of the fourth group were intraperitoneally injected with 50 mg/kg/day L-NAME and then orally, with 50 IU/kg/day vitamin D (group IV). All groups were treated daily from 7 to 14 days of gestation. Results and conclusion The placenta of mice injected with L-NAME showed different phases of histopathological changes in the basal and labyrinth zone. Meanwhile, the kidney in 18-day-old fetuses maternally injected with L-NAME showed an apparent enlargement in the glomerular area and the presence of hemorrhages among the tubules. However, the 18-day-old fetuses maternally treated with L-NAME and vitamin D (group IV) showed mild injury. This study concluded that induced PE-like symptoms in pregnant mice by L-NAME caused increased fetal growth restriction, impairment of placental histology, and histopathology of the kidneys of fetuses. On the other hand, vitamin D ameliorated the effect of L-NAME and reduced the risk of PE.

Pregnancy Disorders: A Potential Role for Mitochondrial Altered Homeostasis.

Pregnancy is a complex and challenging process associated with physiological changes whose objective is to adapt the maternal organism to the increasing energetic requirements due to embryo and fetal development. A failed adaptation to these demands may lead to pregnancy complications that threaten the health of both mothers and their offspring. Since mitochondria are the main organelle responsible for energy generation in the form of ATP, the adequate state of these organelles seems crucial for proper pregnancy development and healthy pregnancy outcomes. The homeostasis of these organelles depends on several aspects, including their content, biogenesis, energy production, oxidative stress, dynamics, and signaling functions, such as apoptosis, which can be modified in relation to diseases during pregnancy. The etiology of pregnancy disorders like preeclampsia, fetal growth restriction, and gestational diabetes mellitus is not yet well understood. Nevertheless, insufficient placental perfusion and oxygen transfer are characteristic of many of them, being associated with alterations in the previously cited different aspects of mitochondrial homeostasis. Therefore, and due to the capacity of these multifactorial organelles to respond to physiological and pathophysiological stimuli, it is of great importance to gather the currently available scientific information regarding the relationship between main pregnancy complications and mitochondrial alterations. According to this, the present review is intended to show clear insight into the possible implications of mitochondria in these disorders, thus providing relevant information for further investigation in relation to the investigation and management of pregnancy diseases.

The Role of MALAT1 in Regulating the Proangiogenic Functions, Invasion, and Migration of Trophoblasts in Selective Fetal Growth Restriction.

Epigenetic regulation is an important entry point to study the pathogenesis of selective fetal growth restriction (sFGR), and an understanding of the role of long noncoding RNAs (lncRNAs) in sFGR is lacking. Our study aimed to investigate the potential role of a lncRNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), in sFGR using molecular biology experiments and gain- or loss-of-function assays. We found that the levels of MALAT1, ERRγ, and HSD17B1 were downregulated and that of miR-424 was upregulated in the placental shares of the smaller twins. Moreover, angiogenesis was impaired in the placental share of the smaller fetus and MALAT1 could regulate the paracrine effects of trophoblasts on endothelium angiogenesis and proliferation by regulating miR-424. In trophoblasts, MALAT1 could competitively bind to miR-424 to regulate the expression of ERRγ and HSD17B1, thus regulating trophoblast invasion and migration. MALAT1 overexpression could decrease apoptosis and promote proliferation, alleviating cell damage induced by hypoxia. Taken together, the downregulation of MALAT1 can reduce the expression of ERRγ and HSD17B1 by competitively binding to miR-424, impairing the proangiogenic effect of trophoblasts, trophoblast invasion and migration, and the ability of trophoblasts to compensate for hypoxia, which may be involved in the pathogenesis of sFGR through various aspects.

Trophoblast fusion in fetal growth restriction is inhibited by CTGF in a cell-cycle-dependent manner.

Fetal growth restriction (FGR) is a relatively common complication of pregnancy, and insufficient syncytialization in the placenta may play an important role in the pathogenesis of FGR. However, the mechanism of impaired formation of the syncytiotrophoblast layer in FGR patients requires further exploration. In the present study, we demonstrated that the level of syncytialization was decreased in FGR patient placentas, while the expression of connective tissue growth factor (CTGF) was significantly upregulated. CTGF was found to inhibit trophoblast fusion via regulating cell cycle progress of BeWo cells. Furthermore, we found that CTGF negatively regulates cell cycle arrest in a p21-dependent manner as overexpression of p21 could rescue the impaired syncytialization induced by CTGF-overexpression. Besides, we also identified that CTGF inhibits the expression of p21 through ITGB4/PI3K/AKT signaling pathway. Our study provided a new insight for elucidating the pathogenic mechanism of FGR and a novel idea for the clinical therapy of FGR.