Placenta Weight Research Articles

Vicissitudes in the Placental Cotyledon Number in a Singleton Pregnancy with Gestational Diabetes.

Background:Placenta is a transient organ during pregnancy, connects the fetus to the uterine wall. Pregnancy is frequently complicated by gestational diabetes, which might cause morphological changes in the placenta (weight, diameter, and cotyledons number); consequently, it may affect both fetus and mother.Aim:The aim of this study was to determine the difference in placental cotyledons number between pregnant with gestational diabetes versus without gestational diabetes, then correlate it with the weight and diameter between groups.Materials and Methods:A comparative study (gestational diabetes Group A and nongestational diabetes Group B) included mothers with a singleton baby delivered at term (37–40 weeks) after acceptance of the informed consent. Women with pregestational diabetes and other chronic diseases and those with intrauterine fetal death were excluded. Postdelivery placentae were accurately prepared and examined in detail. The placental weight, diameter, and cotyledons number were recorded and analyzed by SPSS version 21. The correlation was measured between the two groups in terms of cotyledons count, placental diameter, and weight.Results:The study included 385 participants (128 Group A and 257 Group B). Placental number of cotyledons, weight, and diameter in Group A were higher than in Group B, and the difference was significant (P = 0.000, P = 0.021, and P = 0.000, respectively). In Group A, there was a significant correlation between the placental weight, diameter, and number of its cotyledons (r = 0.23, P = 0.011). Cotyledon count was significantly affected by diabetic control (P = 0.021).Conclusions:Gestational diabetes increases placental cotyledons number, weight, and diameter.

The Role of High Calcium Diet Supplementation on L-NAME induced High Blood Pressure in Pregnant Rats

Background: Hypertension in pregnancy with or without proteinuria is one of the foremost reasons of maternal death and morbidity in the world. This study investigated the role of a high calcium diet (HCa) in N G -nitro-L-arginine methyl ester (L-NAME) administered to pregnant rats. Methods: Thirty-two female rats of the Sprague-Dawley strain were randomly assigned into 4 groups of control, L-NAME (0.3g/ L of water), L-NAME + HCa (2.5%), and HCa diet (2.5%) group. Following confirmation of mating, HCa was administered from day 3 to day 18 of pregnancy while L-NAME was administered from day 12 to 18. The rats were sacrificed on the 19th day and blood pressure measurements were obtained. Blood and placenta were collected for biochemical and oxidative assays. Results: Blood pressure was reduced in L-NAME + HCa rats compared with L-NAME (p<0.05). Placenta and fetal weight were decreased in rats receiving L-NAME, L-NAME + HCa and HCa compared with control (p<0.05). HCa diet had no effect on L-NAME impaired oxidative status. No significant difference was observed in the liver enzymes and CRP levels across the groups. However, there was a significant reduction in the platelet count of L-NAME + HCa and HCa groups when compared with the control and L-NAME. Calcium and magnesium levels in the serum and placenta homogenate were not different but their excretion was significantly increased in the urine samples of the L-NAME + HCa and HCa groups. Conclusion: This study showed that HCa reduced the blood pressure of pregnant rats administered L-NAME but had no effect on oxidative stress. This implies that HCa alone might not sufficiently ameliorate the negative effects of hypertension in pregnancy.

The Protective Role of Vitamin E Against Teratogenic Effects of Nicotine on Embryonic Bone Development

Aim: According to World Health Organization data, around 1.5 billion people in the world use tobacco products. Nicotine, the most common use of tobacco, is the main psychoactive substance that causes addiction. Exposure to nicotine during pregnancy increases the risk of low placenta weight, stillbirth, congenital heart disease, musculoskeletal defect. Antioxidants are used to protect against teratogenic substances such as nicotine. The purpose of the study was to determine the skeletal system malformations caused by low (3 mg/kg) and high (6 mg/kg) doses of nicotine during embryonic bone evolution by using the double skeletal staining method and the protector role of vitamin E in preventing these malformations.Material and Method: The rats were divided into 6 groups: the control, low-dose nicotine, high-dose nicotine, low-dose nicotine+vitamin E, high-dose nicotine+vitamin E and vitamin E. The development of the skeletal system of the fetuses was examined by the skeleton staining method. The anterior and posterior extremity images of the fetuses were examined under the stereomicroscope and then through photographing total bone length, ossification length and ossification rate were calculated in the ImageJ program. Results: There was an important decline in the total bone length, ossification length and ossification rate (p<0.05) in the bone measurements of the front and hind extremities, while it was found that the treatment groups approached the control group and the increases were important (p<0.05). Conclusion: It was concluded that being to nicotine during pregnancy delayed skeletal ossification and that vitamin E, which is an antioxidant, may be protective opposite the teratogenic effect of nicotine on the bone.

Impaired Compensatory Vasodilatory Effect Mediated by Wolfram Syndrome 1 and Corticotropin-Releasing Hormone Family Peptides in 17α-Ethynylestradiol-Induced Intrahepatic Cholestasis Pregnant Rats When Under Additional Acute Hypoxia Stress

Abstract Objective: To investigate the possible regulatory mechanism of corticotropin-releasing hormone (CRH), urocortin (UCN), and Wolfram syndrome 1 (WFS1) in 17α-ethynylestradiol (EE)-induced intrahepatic cholestasis pregnant rats and its ischemia reperfusion (IR) model. Methods: Pregnant rats (n = 60) were randomly divided into four experimental groups by random number table (Control, EE, IR, and EE-IR groups), and were studied on the 17th, 19th, and 21st gestational days (GD) (n = 5 in each group at the indicated time). Growth and development indicators of fetal rats among these four groups were recorded. Enzyme-linked immunosorbent assay was employed to detect CRH, UCN, and WFS1 levels in maternal sera. Western blotting and real-time polymerase chain reaction were used to quantify placental protein and placental mRNA levels of CRH, UCN, and WFS1. Multivariate analysis of variance and least significant difference test were used to establish the group and individual comparisons. Results: A significant difference was found in placenta weight (F = 8.10, P < 0.05), fetal rat weight (F = 40.86, P < 0.05), fetal rat length (F = 61.61, P < 0.05), and fetal rat tail length (F = 55.63, P < 0.05) among four groups on the 17th ,19th , and 21st GD.What's more, the overall differences of maternal serum UCN levels among Control, EE, IR, and EE-IR groups were significant (F = 2.48, P < 0.05). Expression of WFS1 mRNA in the EE-IR group was significantly increased and higher than Control (0.46 ± 0.15 vs. 0.24 ± 0.09, P < 0.05), EE (0.46 ± 0.15 vs. 0.17 ± 0.04, P > 0.05), and IR (0.46 ± 0.15 vs. 0.22 ± 0.15, P > 0.05) groups at 19th GD, indicating that endoplasmic reticulum stress may be activated. However, the expression of CRH (0.42 ± 0.05 vs. 0.58 ± 0.12, P < 0.05), UCN (0.43 ± 0.01 vs. 0.47 ± 0.16, P > 0.05), and WFS1 (0.57 ± 0.07 vs. 0.74 ± 0.12, P > 0.05) protein in the EE-IR group was subsided compared to the IR group at 17th GD. Conclusion: Fetal rat growth restriction was found in the EE-induced intrahepatic cholestasis model. This study revealed that significant changes in the maternal sera level of UCN , placental level of WFS1 mRNA and placental levels of CRH, UCN, and WFS1 protein in chronic versus acute stress in a rat model of pregnancy. This suggests an impaired compensatory vasodilatory effect mediated by these factors at gene transcription and protein translation levels, following acute hypoxia stress in EE-induced intrahepatic cholestasis in pregnant rats.

Effects of gestational diabetes mellitus on the quality and quantity of blood hematopoietic stem cells: a case-control study

AimTo evaluate the effects of gestational diabetes mellitus (GDM) on the quantity and quality of hematopoietic stem cells (HSC).MethodsIn this case-control study, HSC were isolated from umbilical cord blood (UCB) procured at delivery from 63 mothers with GDM and 67 healthy mothers. Total nucleated cells (TNC) and CD34+ cells were quantified using BD FACSCalibur flow cytometer. The quantity and quality of stem cells were determined.ResultsThe GDM group had lower total cord blood volume and lower number of nucleated HSC compared with healthy mothers. Regarding stem cell quantity parameters, they had significantly lower UCB volume (P = 0.041), TNC count (P = 0.022), total viable NC count (P = 0.014), and CD34+ percentage (P = 0.014). Regarding the quality of stem cells, they had significantly lower viable TNC percentage (P = 0.015). The predictors for total TNC count were longer labor duration (adjusted B coefficient [p]: 0.031 [0.046]), greater estimated blood loss (0.089 [0.005]), female neonates (12.322 [0.049]), and higher placenta weight (0.080 [0.033]). The predictors of total viable NC count were greater estimated blood loss (0.092 [0.003]), female neonates (13.16 [0.035]), and greater placenta weight (0.083 [0.026]).ConclusionThe GDM group had much lower quantity and quality of UCB stem cells. Our results should be taken into consideration when drawing cord blood for unrelated stem cell banking in an obstetric unit to ensure the obtaining of optimal cord blood samples and to avoid unnecessary expenses.

Placental Cord Drainage: Its Effect on Duration and Blood loss of Third Stage of Labor

Background: the present study aimed to evaluate the effect of placental cord drainage on duration and blood loss of third stage of labor. Design: Randomized controlled trial was utilized. Setting: The study was performed at delivery unit of Obstetrics and Gynecology Departments, Mansoura University Hospital, Egypt. Subjects: One hundred forty parturient women undergoing normal vaginal delivery attained the inclusion criteria were comprised. The entrants were divided equally by simple randomization into intervention group (n=70 women) who underwent placental cord drainage and control group consisted of (n=70 women) who received the conventional hospital protocol. Tools: Structured interview schedule and labor assessment sheet were used for collecting the data. Results: The mean of third stage assessment parameters showed statistically significant difference, where it was significantly shorter in favor of the intervention group than control group. Time elapsed until appearance of placenta separation signs was (3.657 ± 0.678 vs. 6.514 ± 0.829 min.), duration of 3rd stage was (4.528 ± 0.557 vs. 7.185 ± 0.665 min.) and the amount of blood loss was (192.50 ± 9.545 vs. 289.285 ± 11.711 ml.) respectively. However, there was no statistically significant difference observed between both groups regarding placenta weight. Furthermore, the incidence of relaxed uterus, Postpartum hemorrhage and the need for uterotonic drugs were lower in intervention group in comparison to those in control group by 17.1%, 10% and 10% respectively. 7.1% of control group had retained placenta. Conclusion: The current study findings highlighted that placental cord drainage was an effective method in reducing the duration and blood loss of third stage of labor in normal vaginal deliveries. Recommendations: Placental cord drainage should be encouraged in normal vaginal deliveries and conducting similar studies on a wide range of sample in multicenter settings for generalizing the findings.

Effect Of Virgin Olive Oil (EVOO) On Placenta Weight and Fetal Weight in Preeclampsia Model Wistar Rats

Preeclampsia was defined as new onset hypertension and proteinuria after 20 weeks of gestation in which the mother had no previous history of hypertension. Preeclampsia is a disorder that often occurs in pregnancy with an incidence rate of 2-8% among pregnancies in the world. Preeclampsia ranks 2nd as a cause of maternal death (MMR). In East Java, preeclampsia was ranked 1st as the cause of AKI in 2016. Preeclampsia as one of the main causes of maternal death can be detected and treated properly before the emergence of life-threatening complications such as eclampsia. In severe cases, preeclampsia increases the risk of comorbidities such as Hemolysis, Elevated Liver Enzyme Levels, and Low Platelet Levels (HELLP) syndrome, edema, Disseminated Vascular Coagulation (DIC), and eclampsia/cerebral edema, whereas in fetus preeclampsia is associated with intrauterine growth restriction. (IUGR), prematurity and fetal death. Extra virgin olive oil (EVOO) is obtained from olives in a mechanical way that does not change the composition of the oil. Research on EVOO has been widely studied in a broad spectrum which explores its content as antioxidants and also anti-inflammatory polyphenols and tocopherols that can be used as anti-oxidants and also anti-inflammatory. The purpose of this study was to prove the role of EVOO on placental and fetal weight in preeclampsia model Wistar rats. The design of this study was experimental (quasi experimental) with a posttest only control group design approach. This study consisted of 5 groups, negative group, positive group (preeclampsia model rats), treatment groups 1, 2 and 3, namely preeclampsia rats that were given EVOO in 3 different doses (each 0.5ml/day, 1ml/day, 2 ml/day). After being sacrificed, the placenta and fetus are weighed to determine their weight. The results showed that the administration of EVOO was effective in increasing the weight of the placenta and fetus in preeclampsia model rats with a P value of 0.000 (P<0.05).

Early life factors in relation to albuminuria and estimated glomerular filtration rate based on cystatin C and creatinine in adults from a Swedish population-based cohort study

BackgroundEarly life factors influence the number of nephrons a person starts life with and a consequence of that is believed to be premature kidney ageing. Thus, we aimed to identify early life factors associated with cystatin C and creatinine-based estimated glomerular filtration (eGFR) rate equations and urine -albumin-to-creatinine ratio after a follow-up of 46–67 years.MethodsThe study included 593 Swedish subjects without diabetes mellitus from the Malmo Diet Cancer Cohort. Perinatal data records including birth weight, gestational age, placenta weight and maternal related risk factors were analysed. eGFR was determined by Chronic Kidney Disease Epidemiology (CKD-EPI), the Lund-Malmö revised and Caucasian, Asian, Paediatric, and Adult (CAPA) equations. Postnatal growth phenotypes were defined as low (≤ 0) or high (> 0) birth weight z-score, or low (≤ median) or high (> median) body mass index at 20 years of age.ResultsIn women, lower birth weight was associated with lower eGFR (CAPA; CKD-EPI cystatin C). Birth weight z-score predicted adult albuminuria specifically in men (OR 0.75, 95% CI [0.58; 0.96]). Women with high birth weight z-score and low BMI at 20 years had lower eGFR (CAPA; CKD-EPI cystatin C; p = 0.04). Men with high birth weight z-score and high BMI at 20 years had lower risk for albuminuria (OR 0.35, 95% CI [0.12; 0.93]).ConclusionsLower birth weight, prematurity and postnatal growth curve have a potential sex- specific effect of early exposure to an adverse environment on lower cystatin C-based eGFR and albuminuria later in life. Cystatin C compared to creatinine -eGFR equations shows a higher ability to detect these findings.Graphic abstract

PSVII-3 Evaluation of dietary OmniGen AF supplementation and PG600 injection on reproductive characteristics of gilts

Abstract A cooperative study evaluated effects of supplemental dietary OmniGen AF (OG; Phibro Animal Health Corporation) on reproductive characteristics of gilts. Crossbred gilts (n = 56; initial body weight = 152.3 ± 9.7 kg) were assigned to treatments in a 2 x 2 factorial design [diet (OG or control) and PG600 (Merck Animal Health, El Dora, KS) injection (Yes or No)]. Dietary treatments were: 1) corn-SBM basal diet (control) that met NRC (2012) requirement estimates, or 2) control plus 0.75% OG and were fed 35 to 40 d prior to breeding. A common diet formulation was used by both stations. Gilts were estrous-synchronized by 14-d feeding of Matrix (Merck Animal Health). PG600 injections occurred 24 hours after Matrix withdrawal. Gilts were weighed at breeding and preslaughter (at d 39 to 48 postbreeding) and were euthanized to evaluate reproductive characteristics. There were no OG x PG600 interactions on any response measures (P > 0.15). Mean responses did not differ (P > 0.20) when gilts were fed control or OG diets, respectively, for total uterus weight (6,065 vs. 5,883 g), uterine horn length (129.2 vs. 123.9 cm), ovary weight (9.66 vs. 9.94 g), total corpora lutea (CL) number (25.0 vs. 25.3), individual CL weight (0.41 vs. 0.43 g), total follicular fluid weight (3.17 vs. 3.03 g), individual placenta weight (86.3 vs. 86.4 g), total fetuses (14.2 vs. 13.0), and fetus crown-rump length (7.97 vs. 7.66 cm). Supplementation with OG reduced (P = 0.04) individual placenta fluid volume of gilts (150.6 vs. 115.4 mL). PG600 injection increased (P < 0.001) ovary weight (9.03 vs. 10.57 g), total CL (18.09 vs 32.27) and reduced CL weight (0.46 vs. 0.38 g). The results demonstrated classic PG600 responses on reproductive characteristics but no effects of 0.75% OG supplementation nor an interaction between the two factors.

Phoenixin-20 ameliorates gestational diabetes mellitus (GDM) symptoms and placental insults in an experimental mouse model

Background and purposeGestational diabetes mellitus (GDM) is a complication commonly observed in pregnancy, closely associated with increased oxidative stress, inflammatory response, and endoplasmic reticulum (ER) stress. Phoenixin-20 (PNX-20) is a newly reproductive hormone from the hypothalamus that has displayed pleiotropic effects. The promising inhibitory effects of PNX-20 on inflammation have recently been widely reported. The present study aims to investigate the protective effect of PNX-20 on GDM induced placental insults. MethodsA GDM model was established on C57BLKsJ db/+ mice. The expression level of GPR173 was evaluated using RT-PCR and western blotting analysis. The serum level of glucose, insulin, lipid profiles, and oxidative stress indicators were detected with commercial kits. Fetal analysis was performed to evaluate the reproductive ability. ELISA was used to detect the production of inflammatory factors. The expressions of p-eIF-2α, ATF4, and GRP78 were evaluated with western blotting assay. ResultsFirstly, we found that GPR173 is expressed in the placenta tissue. Secondly, the elevated blood glucose level and lipid level, declined serum insulin level, fetus alive ratio, fetal and placenta weight, and shorten crown-rump length, were observed in the placenta tissue of GDM mice, which were reversed by treatment with PNX-20. Thirdly, the excessively released inflammatory factors and activated oxidative stress in GDM mice were alleviated by the administration of PNX-20. Lastly, the activated eIF-2α/ATF4 ER stress signaling pathway in GDM mice was dramatically suppressed by PNX-20. ConclusionOur data revealed a protective property of PNX-20 against placental insults resulted from GDM.

TNFα blockade reverses vascular and uteroplacental matrix metalloproteinases imbalance and collagen accumulation in hypertensive pregnant rats

Preeclampsia is a pregnancy-related disorder of maternal hypertension-in-pregnancy (HTN-Preg) and often fetal growth restriction (FGR). Placental ischemia could be an initiating event leading to inadequate vascular and uteroplacental remodeling and HTN-Preg; however, the molecular targets are unclear. To test the hypothesis that placental ischemia-induced release of proinflammatory cytokines target vascular and uteroplacental matrix metalloproteinases (MMPs), we tested if infusing TNFα (200 ng/kg/day) in day-14 pregnant (Preg) rats causes MMP imbalance and collagen accumulation, and if infusing TNFα decoy receptor Etanercept (0.4 mg/kg/day) in HTN-Preg rats with reduced uteroplacental perfusion pressure (RUPP) reverses MMP imbalance and collagen accumulation. On gestational day-19, blood pressure (BP) was higher in Preg + TNFα and RUPP vs Preg rats, and restored in RUPP + Etanercept rats. Gelatin zymography and Western blots revealed decreases in MMP-2 and MMP-9 and increases in MMP-1 and MMP-7 in aorta, uterus and placenta of Preg + TNFα and RUPP, that were reversed in RUPP + Etanercept rats. Collagen-I and IV were abundant in Preg + TNFα and RUPP, and were decreased in RUPP + Etanercept rats. The litter size, uterine, placenta, and pup weight were markedly reduced in RUPP, insignificantly reduced in Preg + TNFα, and slightly improved in RUPP + Etanercept rats. Thus TNFα blockade reverses the decreases in vascular and uteroplacental MMP-2 and MMP-9, and the increases in MMP-1, MMP-7 and accumulation of collagen-I and IV induced by placental ischemia and TNFα in HTN-Preg rats. Targeting TNFα using cytokine antagonists, or MMPs using MMP modulators could rectify MMP imbalance and collagen accumulation, restore vascular and uteroplacental remodeling, and improve BP in HTN-Preg and preeclampsia.

Fetal Outcomes of Abnormal Placental and Birth Weight Ratio

Objective: To find out the fetal complications of abnormal placental and birth weight ratio.
 Materials and methods: This is a cross sectional study conducted from January 2019 to January 2020 at department of Gyn/Obs PMCH Nawabshah. Total 110 patients who met the criteria were included in this study. After history, clinical examination and required radiological and biochemical investigations, participants were delivered and weight of placenta and bay was measured and ratio was recorded. Results were made and conclusion was drawn.
 Results: Age difference was also seen in participants. Maternal age ranged from 18-35 years. 65(59%) patients ranged from 18 to 25 years. 30(27%) patients were of age between 26-30 years. 16(14%) aged from 31-35 years. Regarding fetal outcomes, Intra Uterine Growth Retardation (IUGR) was found to be among 30(27.27%), IUD in 3(2.72%), fetal distress in10 (9.09%), low APGAR in 7(6.36%), respiratory distress in 6(5.45%) and Cardio Vascular Diseases in 0% patients.
 Conclusion: To sum up, it is concluded that in our study, the common fetal outcome due to abnormal Abnormal Placental And Birth Weight Ratio (PBWR) was intra uterine growth retardation (IUGR) followed by IUD, fetal distress and low APGAR.

The Effects of Sperm and Seminal Fluid of Immunized Male Mice on In Vitro Fertilization and Surrogate Mother–Embryo Interaction

The latest vaccination campaign has actualized the potential impact of antigenic stimuli on reproductive functions. To address this, we mimicked vaccination’s effects by administering keyhole limpet hemocyanin (KLH ) to CD1 male mice and used their sperm for in vitro fertilization (IVF). Two-cell embryos after IVF with spermatozoa from control (C) or KLH-treated (Im) male mice were transferred to surrogate mothers mated with vasectomized control (C) or KLH-treated (Im) male mice, resulting in four experimental groups: C–C, Im–C, C–Im, and Im–Im. The pre-implantation losses were significantly lower in the Im–C group than in the C–Im group. At the same time, the resorption rates reduced markedly in the C–Im compared to the Im–C group. Embryo and placenta weights were significantly higher in the Im–Im group. Although the GM-CSF levels were lower in the amniotic fluid of the gestating surrogate mothers in the Im–Im group, they were strongly correlated with embryo mass. The number–size trade-off was only significant in the Im–Im group. This suggests a positive, cooperative effect of spermatozoa and seminal fluid from immune-primed males on embryo growth and the optimal distribution of surrogate mother maternal resources despite the negative impact of males’ antigenic challenge on the IVF success rate.

Regulatory role of Apelin-13-mediated PI3K/AKT signaling pathway in the glucose and lipid metabolism of mouse with gestational diabetes mellitus

ObjectiveTo investigate the regulatory mechanism of Apelin-13-mediated PI3K/AKT signaling pathway in the glucose and lipid metabolism of gestational diabetes mellitus (GDM) mouse. MethodsGDM mice models were established and treated with Apelin-13 and/or PI3K/AKT inhibitor LY294002. Then, the indicators of glucose and lipid metabolism and the levels of inflammatory factors were detected. Besides, the levels of indicators of oxidative stress in the placenta of mice were measured. Western blotting was also carried out to determine the expression of PI3K/AKT pathway-related proteins in all groups. ResultsIn comparison with the Control group, mice in the GDM group presented with the continuous increase in the level of FBG as the time went on, while FINS level decreased evidently. Besides, the fetus alive ratio in the GDM group was much lower with significant increased weight of fetal mouse and weight of placenta; the mice had significant decreased levels of IL-6, IL-1β, TNF-α and MCP-1, and in the placenta, the levels of SOD, GPx, GSH and CAT were also reduced evidently, with significant downregulation of p-PI3K/PI3K and p-AKT/AKT. However, indicators above in the GDM mice treated with Apelin-13 had significant improvement as compared to those in the GDM group, and the improvement was reversed by LY294002 treatment. ConclusionApelin-13, possibly by activating the PI3K/AKT pathway, could improve the glucose and lipid metabolism, reduce the damage caused by oxidative stress and inflammatory reaction, and protect the pancreas islet, thereby improving the pregnancy outcome of GDM mice.

PLATELET-RICH PLASMA INCREASES HIF1a AND HIF2a IN ENDOMETRIUM AFFECTING LIVE BIRTH RATES IN MURINE ASHERMAN’S SYNDROME MODEL

Women with refractory thin endometrium suffering from recurrent implantation failure (RIF) do not have many effective treatment options. Platelet-rich plasma (PRP) has been noted to be a possible breakthrough for these patients in several clinical studies. Also, hypoxia-inducible factor 1-alpha (HIF1a) and HIF2a are recently being studied to have some connection with endometrial function. The objective of this study was to find out the underlying mechanism of PRP acting on refractory endometrium and its possible relationship with HIF1a/HIF2a. Murine Asherman’s syndrome (AS) models were made by inducing damage to the uterine horns and human PRP obtained from 6 RIF patients was applied by intrauterine injection at day 7 after injury. RT-PCR analyses and western blotting of fibrosis, angiogenic markers and embryo invasion related markers from the mouse endometrial specimen were done at day 7 after PRP treatment. Cell migration study (scratch test) was done to see the recovery rate of the damaged human endometrial cell after PRP treatment. Implantation and live birth rates were compared between mouse AS model with and without PRP treatment. T-test was used for statistical analysis with SPSS ver.26. RT-PCR analyses showed significant decreases in fibrosis markers (COL1a1, p = 0.041; TIMP1, p = 0.027; TGF-b1, p = 0.004; TNF-a, p = 0.047) and significant increases in angiogenic markers (VEGF-a, p = 0.047; ANG-1, p = 0.015; HGF p = 0.031) including HIF1a (p = 0.023) and HIF2a (p = 0.042). The embryo invasion related markers including LIF (p = 0.001), MT2-MMP (p = 0.001), LOX (p < 0.001), and ADM (p < 0.001) were significantly increased after PRP treatment in AS models. Western blot also revealed similar results as RT-PCR. Cell migration study showed significantly higher migration rate for PRP group compared to control. The number of implantation sites and live birth rates were significantly greater in PRP group compared to AS without treatment. No live pup was delivered from AS without PRP mouse group. The embryo and placenta weights were significantly greater in PRP treated group (p < 0.001). PRP has shown to improve the damaged endometrium by decreasing fibrosis, increasing angiogenesis and embryo invasion markers. HIF1a and HIF2a seem to be the key factors that are increased by PRP. In return, they affect the embryo implantation by inducing LOX, MT2-MMP in endometrial epithelial detachment, and LIF which regulates embryo attachment.

Folic acid Supplementation on placental Interleukin-6 and offspring growth in prenatal stress mice model

Introduction: Stress during pregnancy affects physical and psychological change, resulting in wide range of mild to severe abnormalities including inflammation, abberant placentation, fetal growth defect, and the decrease quality of life in the fetus’ adulthood. Previous study showed that Folic Acid (FA) has the potential effect in the pregnant and fetus’ prosperities due to the protective properties in the embryogenesis. To that end, we created the stress mice model and treated with FA, assessment was obtained by the expression of IL-6 in placenta and birth weight observation to reflect the fetus quality. Methods: subjects were 21 pregnant mice (Mus musculus) that divided into three groups (n=7) comprised of normal pregnant mice, stress mice model, and stress mice model treated with FA groups. Stress induction started from gestational day (gd) 10 to gd-15 by chronic restrain stress and 379 lux bright light exposure each twice-a-day within 30 minutes to induce depressive and anxiety-like behaviours. Folic acid treatment was begun with the similar time with the stress induction by dose dependent 3 mg/kg bw/day once a day prior the stress induction. On gd-16, mice were euthanized and fetal weight was examined followed by placental tissue collection for immunochemistry staining. Results: Placental IL-6 expression were not statistically different in stressed pregnant-mice treated by folic acid (p=0.077). There was a significant difference in fetal weight (p= 0.0001). In addition, the expression of placental IL-6 was associated with fetal weight (p= 0.021). Conclusions: The FA treatment has the ability to increase the fetal birth weight but unable to decrease the IL-6 as the pro-inflammatory cytokine in stress-induced mice.

Efficacy of Low Molecular Heparin on Preeclampsia by Inhibiting Apoptosis of Trophoblasts via the p38MAPK Signaling Pathway.

Objective To explore the efficacy of low molecular heparin on preeclampsia by inhibiting apoptosis of trophoblasts via the p38MAPK signaling pathway. Methods A preeclampsia rat model was established, and the effects of low molecular heparin on preeclampsia via the p38MAPK signaling pathway were analyzed based on intervention of the rats with different combinations of low molecular heparin and p38MAPK signaling pathway activator. Furthermore, a hypoxia/reoxygenation model of trophoblasts in vitro was established to explore the effects of low molecular heparin on trophoblasts via the p38MAPK signaling pathway. Results After treatment with low molecular heparin, pregnant rats in the heparin group showed significantly decreased blood pressure, 24 h proteinuria, and p38MAPK protein levels in placenta tissues and decreased apoptosis rate of placenta tissue cells (all P < 0.05) and showed more fetal rats and lowered weight of them (both P < 0.05) but showed no significant change in the weight of placenta (all P > 0.05). Pregnant rats treated with low molecular heparin and p38MAPK activator showed significantly higher blood pressure, 24 h proteinuria, and p38MAPK protein levels in placenta tissues and apoptosis rate of placenta tissue cells than those of pregnant rats in the heparin group (all P < 0.05) and also showed less fetal rats and lighter fetal rats than those in the heparin group (both P < 0.05) but showed no difference with them in the weight of placenta (P > 0.05). Further analysis revealed that low molecular heparin could protect the survival and migration of trophoblasts under hypoxia/reoxygenation conditions and reduce apoptosis of them (all P < 0.05). Conclusion Low molecular heparin can alleviate preeclampsia by inhibiting the p38MAPK signaling pathway and can inhibit apoptosis of trophoblasts and promote proliferation and migration of them.

The asthma predictive index as a surrogate diagnostic tool in preschoolers: Analysis of a longitudinal birth cohort.

To evaluate if the asthma predictive index (API) can be used as surrogate for asthma diagnosis in preschoolers. Birth cohort of 339 pregnant women enrolled at delivery and their offspring, who were followed for atopy, wheezing, and other respiratory illnesses through 30 months of age. The API was determined at 30 months of age by the researchers; and examined its association with physician-diagnosed asthma during the first 30 months, made independently by the primary care physician not involved in the study. Among 307 offspring with complete follow-up, 44 (14.3%) were API+. Maternal body mass index, maternal education, past oral contraceptive use, birthweight, placenta weight, age of daycare at 12 m, gastroesophageal reflux disease at 12 m, acute otitis media at 18 m, bronchiolitis, croup and pneumonia, cord blood adiponectin were all associated with API+. In the multivariable analysis, API+ was associated with almost sixfold odds of asthma diagnosis (adjusted OR = 5.7, 95% CI [2.6-12.3]), after adjusting for the relevant covariates above including respiratory infections like bronchiolitis and pneumonia. The API sensitivity was 48%, specificity 92%, 61% PPV, 88% NPV, 6.4 LR+, 0.56 LR-, 0.84 diagnosis accuracy. The adjusted odds for asthma was 11.4. This longitudinal birth cohort suggests, for first time, that API (a structured definition for asthma), could be used as a diagnostic tool, not only as a prognostic tool, in toddlers and preschoolers.

FGF15/FGF19 alleviates insulin resistance and upregulates placental IRS1/GLUT expression in pregnant mice fed a high-fat diet

IntroductionThis study aimed to evaluate whether FGF19 can alleviate insulin resistance and change the expression of placental IRS1/GLUTs. MethodsMice transgenic for Fgf15 (the murine homologue of human FGF19) were constructed, and human recombinant FGF19 was administered to pregnant high-fat diet mice. Then, glycolipid metabolism parameters and the weight of foetus and placenta were observed. The expression levels of key molecules of the insulin signalling pathway and glucose transporters in placentae were detected by qRT-PCR and western blotting. Primary trophoblasts and JAR cells were cultured in high-glucose medium, and FGF19 was added to observe its regulatory effects on IRS1/GLUTs. ResultsOverexpressing FGF15 or exogenously administering FGF19 reduced the levels of fasting blood glucose, HOMA-IR, triglycerides, and free fatty acids in pregnant high-fat diet mice compared to control mice (P < 0.05). FGF15/FGF19 did not significantly affect placental weight, foetal weight or litter size (P > 0.05). In addition, FGF15/FGF19 upregulated the expression of p-IRS1 and GLUT4 in the placentae of high-fat diet mice and upregulated GLUT1 levels in the placentae of normal diet-fed mice (P < 0.05), while it did not significantly alter total IRS1 and GLUT3 levels (P > 0.05). Consistent with the results of the animal experiments, FGF19 increased the expression of p-IRS1 and GLUT4 in trophoblast cells cultured in high-glucose medium (P < 0.05). DiscussionOverexpressing FGF15 or administering FGF19 to pregnant high-fat diet mice can improve glycolipid metabolism and alleviate systemic and local insulin resistance. The possible underlying mechanism may involve upregulation of placental expression of p-IRS1 and GLUT4.

Comparing the Predictivity of Human Placental Gene, microRNA, and CpG Methylation Signatures in Relation to Perinatal Outcomes.

Molecular signatures are being increasingly integrated into predictive biology applications. However, there are limited studies comparing the overall predictivity of transcriptomic versus epigenomic signatures in relation to perinatal outcomes. This study set out to evaluate mRNA and microRNA (miRNA) expression and cytosine-guanine dinucleotide (CpG) methylation signatures in human placental tissues and relate these to perinatal outcomes known to influence maternal/fetal health; namely, birth weight, placenta weight, placental damage, and placental inflammation. The following hypotheses were tested: (1) different molecular signatures will demonstrate varying levels of predictivity towards perinatal outcomes, and (2) these signatures will show disruptions from an example exposure (ie, cadmium) known to elicit perinatal toxicity. Multi-omic placental profiles from 390 infants in the Extremely Low Gestational Age Newborns cohort were used to develop molecular signatures that predict each perinatal outcome. Epigenomic signatures (ie, miRNA and CpG methylation) consistently demonstrated the highest levels of predictivity, with model performance metrics including R2 (predicted vs observed) values of 0.36-0.57 for continuous outcomes and balanced accuracy values of 0.49-0.77 for categorical outcomes. Top-ranking predictors included miRNAs involved in injury and inflammation. To demonstrate the utility of these predictive signatures in screening of potentially harmful exogenous insults, top-ranking miRNA predictors were analyzed in a separate pregnancy cohort and related to cadmium. Key predictive miRNAs demonstrated altered expression in association with cadmium exposure, including miR-210, known to impact placental cell growth, blood vessel development, and fetal weight. These findings inform future predictive biology applications, where additional benefit will be gained by including epigenetic markers.