Significant Decrease In Fetal Weight Research Articles

Safety of embryo cryopreservation: insights from mid-term placental transcriptional changes

BackgroundIn recent years, with benefits from the continuous improvement of clinical technology and the advantage of fertility preservation, the application of embryo cryopreservation has been growing rapidly worldwide. However, amidst this growth, concerns about its safety persist. Numerous studies have highlighted the elevated risk of perinatal complications linked to frozen embryo transfer (FET), such as large for gestational age (LGA) and hypertensive disorders during pregnancy. Thus, it is imperative to explore the potential risk of embryo cryopreservation and its related mechanisms.MethodsGiven the strict ethical constraints on clinical samples, we employed mouse models in this study. Three experimental groups were established: the naturally conceived (NC) group, the fresh embryo transfer (Fresh-ET) group, and the FET group. Blastocyst formation rates and implantation rates were calculated post-embryo cryopreservation. The impact of FET on fetal growth was evaluated upon fetal and placental weight. Placental RNA-seq was conducted, encompassing comprehensive analyses of various comparisons (Fresh-ET vs. NC, FET vs. NC, and FET vs. Fresh-ET).ResultsReduced rates of blastocyst formation and implantation were observed post-embryo cryopreservation. Fresh-ET resulted in a significant decrease in fetal weight compared to NC group, whereas FET reversed this decline. RNA-seq analysis indicated that the majority of the expression changes in FET were inherited from Fresh-ET, and alterations solely attributed to embryo cryopreservation were moderate. Unexpectedly, certain genes that showed alterations in Fresh-ET tended to be restored in FET. Further analysis suggested that this regression may underlie the improvement of fetal growth restriction in FET. The expression of imprinted genes was disrupted in both FET and Fresh-ET groups.ConclusionBased on our experimental data on mouse models, the impact of embryo cryopreservation is less pronounced than other in vitro manipulations in Fresh-ET. However, the impairment of the embryonic developmental potential and the gene alterations in placenta still suggested it to be a risky operation.

The adverse effects of vitrification on mouse embryo development and metabolic phenotype in offspring.

Embryo vitrification is a standard procedure in assisted reproductive technology. Previous studies have shown that frozen embryo transfer is associated with an elevated risk of adverse maternal and neonatal outcomes. This study aimed to explore the effects of mouse blastocyst vitrification on the phenotype of vitrified-warmed blastocysts, their intrauterine and postnatal development, and the long-term metabolic health of the derived offspring. The vitrified-warmed blastocysts (IVF + VT group) exhibited reduced mitochondrial activity, increased apoptotic levels, and decreased cell numbers when compared to the fresh blastocysts (IVF group). Implantation rates, live pup rates, and crown-rump length at E18.5 were not different between the two groups. However, there was a significant decrease in fetal weight and fetal/placental weight ratio in the IVF + VT group. Furthermore, the offspring of the IVF + VT group at an age of 36 weeks had reduced whole energy consumption, impaired glucose and lipid metabolism when compared with the IVF group. Notably, RNA-seq results unveiled disturbed hepatic gene expression in the offspring from vitrified-warmed blastocysts. This study revealed the short-term negative impacts of vitrification on embryo and fetal development and the long-term influence on glucose and lipid metabolism that persist from the prenatal stage into adulthood in mice.

Exploration of Maternal and Fetal Toxicity Risks for Metronidazole-Related Teratogenicity and Hepatotoxicity through an Assessment in Albino Rats.

Metronidazole is the primary antimicrobial drug for treating acute and chronic vaginal pathogens during pregnancy; however, there has been insufficient research on placental disorders, early pregnancy loss, and preterm birth. Here, the potential activity of metronidazole on pregnancy outcomes was investigated. 130 mg/kg body weight of metronidazole was orally given individually to pregnant rats on gestation days 0-7, 7-14, and 0-20. Pregnancy outcome evaluations were carried out on gestation day 20. It was demonstrated that metronidazole could induce maternal and fetal hepatotoxicity. There is a significant increase in the activities of maternal hepatic enzymes (ALT, AST, and ALP), total cholesterol, and triglycerides compared with the control. These biochemical findings were evidenced by maternal and fetal liver histopathological alterations. Furthermore, metronidazole caused a significant decrease in the number of implantation sites and fetal viability, whereas it caused an increase in fetal lethality and the number of fetal resorptions. In addition, a significant decrease in fetal weight, placental weight, and placental diameter was estimated. Macroscopical examination revealed placental discoloration and hypotrophy in the labyrinth zone and the degeneration of the basal zone. The fetal defects are related to exencephaly, visceral hernias, and tail defects. These findings suggest that the administration of metroniazole during gestation interferes with embryonic implantation and fetal organogenesis and enhances placental pathology. We can also conclude that metronidazole has potential maternal and fetal risks and is unsafe during pregnancy. Additionally, it should be strictly advised and prescribed, and further consideration should be given to the associated health risks.

Pregnancy Outcomes in A Group Egyptian Patients with Systemic Lupus Erythematosus: A Cohort Study

Abstract Background Systemic lupus erythematosus (SLE) predominantly affects women of childbearing age thus pregnancy in lupus patients is a common clinical scenario. SLE adversely affects pregnancy outcomes and pregnancy leads to SLE flares Aim of the work Determining the frequencies and predictors of maternal and fetal pregnancy outcomes in women with SLE by a prospective cohort study Patients and methods seventy-one pregnant lupus patients were followed prospectively, and their data compared to age-matched pregnant healthy controls attending Ain Shams University Hospital clinics Results Thirteen Patients had activity at conception. Sixty-six(93%) Where on treatment. Flares occurred in 51 patients (72%) during pregnancy with nephritis being the most common occurring in 78%. The prevalence of anemia, AKI and hypertension (HTN) during pregnancy were higher in SLE group than control group (P < 0.01). The rate of delivery by Cesarean section (CS), PTL, postpartum hemorrhage, preeclampsia (PE), severe PE and HELLP were higher in SLE group then control group (P < 0.01) as well as an increase in rate of postpartum infection (P < 0.05). There was an increase in rate of fetal loss, prematurity, intrauterine growth restriction (IUGR), NICU admission, still birth/intrauterine fetal death and highly significant decrease in fetal weight in SLE group than control group (P < 0.01). Pregestational HTN was independently associated with PE (OR 91.228; CI 6.791-1225.538). Proteinuria and HTN during pregnancy were independently associated with prematurity (OR 14.162 CI 1.029-194.958 & OR 10.596, CI 1.460-76.894). Conclusion Pregnancy in lupus patients carries a higher risk of pregnancy morbidity and worse fetal outcomes than the controls.

Aspirin Ameliorates Preeclampsia Induced by a Peroxisome Proliferator-Activated Receptor Antagonist.

Reduced expression of peroxisome proliferator-activated receptor γ (PPARγ) in the placenta was found in women with severe preeclampsia. Aspirin is currently used as the only recommended intervention in pregnancies for prevention of preeclampsia. In this study, we aimed to investigate whether aspirin could attenuate PPARγ inhibitor (T0070907)-induced preeclampsia and its impact on expression of PPARγ. Sixty Sprague-Dawley rats were used and treated with different doses of aspirin (0, 1, and 1.5 mg/kg) in presence or absence of PPARγ antagonist, T0070907. We found that mean arterial blood pressure was significantly reduced by aspirin treatment in T0070907-exposed rats. T0070907 exposure also led to significant decrease in fetal weight and increase in placental weights. However, 1.5 mg/kg of aspirin reversed these effects of T0070907. Additionally, aspirin also reversed T0070907-induced changes in the levels of thromboxane B2, vascular endothelial growth factor, soluble fms-like tyrosine kinase, and matrix metalloproteinase 2 in both maternal blood and placental tissue. The increased messenger RNA and protein levels of Cox1 and Cox2 induced by T0070907 were markedly reduced by aspirin treatment. Importantly, T0070907 repressed both transcriptional and translational levels of PPARγ, which were reversed by aspirin. In conclusion, this study suggests that aspirin prevented the occurrence of preeclampsia, which is possibly through enhancing both transcriptional and translational levels of PPARγ.

A study of plasma corticosterone levels in an intrauterine growth restricted rat model at prenatal E19 and postnatal P14

A role of fetal exposure to maternal steroids is suggested as a potential mechanism that contributes to the developmental programming of adult CV risk. We hypothesize that the placenta of the IUGR fetus has a higher levels of corticosterone leading to a reduction in placental size and that transmission of maternal steroids to the fetus may serve as a potential mediator of later programmed CV risk. At day 14 gestation RUPP was performed on pregnant rat dams with sham surgeries performed on Control pregnant rat dams. Fetuses were sacrificed at E19 and E20 and P14. Sampling indicated a significant decrease in fetal weight and PW at E19 in the IUGR compared to the Control fetus; PW was significantly decreased at E20 in IUGR compared to Control. However, placental efficiency was significantly higher in IUGR relative to Control at E19 and E20. BW was significantly decreased in IUGR pups compared to Control. A significant increase in plasma levels of corticosterone were observed at E19 in RUPP compared to E19 Control dams; circulating corticosterone levels were also significantly increased in P14 RUPP dams. However, fetal plasma corticosterone levels were not altered in IUGR at E19 compared to Control. In conclusion, early measurements indicated that IUGR fetal weight and weight at birth were significantly reduced by placental insufficiency; however, placental efficiency was increased perhaps indicative of a compensatory mechanism.

Sibutramine Effects on the Reproductive Performance of Pregnant Overweight and Non-Overweight rats

It is well established that sibutramine produces weight loss and is used frequently in women of childbearing age. However, the potential adverse consequences attributed to sibutramine use by women who may become pregnant is not known. It was thus of interest to determine the effects of sibutramine on the reproductive performance of pregnant rats. Overweight as well as non-overweight female Wistar rats were treated with sibutramine (6 mg/kg) orally, daily for 15 d and then mated with normal male rats. Pregnancy was confirmed and treatment continued with sibutramine until d 14 of pregnancy. On d 20 of pregnancy all rats were anesthetized for determination of various maternal and fetal parameters. There was a significant maternal weight reduction at the end of pregnancy in the non-overweight drug-treated group compared to the control (non-overweight, no drug). Sibutramine alone and overweight condition alone produced a significant increase in postimplantation loss and placental index. In the overweight with or without sibutramine groups a significant decrease in fetal weight was noted. Data suggest that sibutramine alone or the condition of excess weight in the absence of drugs produced impaired reproductive performance. However, treatment of overweight rats with sibutramine did not further exacerbate fetal loss compared to sibutramine alone or the effects noted with excess weight alone.

Developmental toxic effects of ethylbenzene or toluene alone and in combination with butyl acetate in rats after inhalation exposure

First, the developmental toxic potential of n-butyl acetate (BA) was examined in Sprague-Dawley rats following whole body inhalation exposure, 6 h day(-1), from day 6 to 20 of gestation, at concentrations of 0, 500, 1000, 2000 and 3000 ppm. Maternal toxicity was evidenced by significant decreases in body weight gain at 2000 and 3000 ppm, and by reduced food consumption at 1000 ppm and higher concentrations. The effects on prenatal development were limited to a significant decrease in fetal weight at 3000 ppm. Thus, inhaled BA was not a selective developmental toxicant. In the second part of this study, the developmental toxic effects of simultaneous exposures to ethylbenzene (EB) and BA, or to toluene (TOL) and BA were evaluated. Pregnant rats were administered EB (0, 250 or 1000 ppm) and BA (0, 500 or 1500 ppm), or TOL (0, 500 or 1500 ppm) and BA (0, 500, 1500 ppm), separately and in combinations, using a 2 x 2 factorial design. The maternal weight gain was reduced after exposure to 1000 ppm EB, to 1500 ppm BA, or to 1500 ppm TOL, either alone or in binary combinations. A significant reduction of fetal weight was associated with exposure to 1000 ppm EB alone, to either mixtures of EB with BA, or to 1500 ppm TOL alone or combined with BA at either concentration. No embryolethal or teratogenic effects were observed whatever the exposure. There was no evidence of interaction between EB and BA or between TOL and BA in causing maternal or developmental effects.

Effect of Gestational Nutrition on Vascular Integrity in the Murine Placenta

Maternal undernutrition is thought to result in smaller offspring and programme disease in later life. It is not known whether gestational nutrition affects development and functioning of placental vessels. The aim of this study was to ascertain if disturbed angiogenesis and junctional integrity were features of the labyrinthine vessels of placenta taken from transgenic Tie2-GFP mice fed either 18% (control) or 9% (low protein; MLP) casein diet.MLP animals showed a significant decrease in fetal weight at E14.5 and in placental and fetal weight at E18.5, however, maternal weight and litter size remained unaffected. Stereological analyses revealed that the fraction of components of the placenta remained similar in both study groups. There was a significant reduction in labyrinthine blood vessel length but not in luminal diameter in the E18.5 MLP group. In both MLP groups, perturbation of vascular endothelial Cadherin and β-catenin, regulators of junctional integrity, permeability and quiescence, was observed with higher percentage of vessels showing weak or no junctional immunoreactivity. The reduction in length of the labyrinthine vessels and the downregulation of the adhesion molecules suggest that gestational undernutrition causes vascular dysfunction in the murine placenta. This may play a role in the early life programming of disease risk.

Evaluation of the protective activity of deferiprone, an aluminum chelator, on aluminum-induced developmental toxicity in mice.

Since deferiprone can be an effective chelating agent for the treatment of aluminum (Al) overload, in the present study we investigated whether this chelator could protect against Al-induced maternal and developmental toxicity in mice. A single oral dose of Al nitrate nonahydrate (1,327 mg/kg) was given on gestation day 12, the most sensitive time for Al-induced maternal and developmental toxic effects in mice. At 2, 24, 48, and 72 hr thereafter, deferiprone was given by gavage at 0 and 24 mg/kg. Cesarean sections were performed on day 18 of gestation and fetuses were examined for malformations and variations. Aluminum-induced maternal toxicity was evidenced by significant reductions in body weight gain, corrected body weight change, and food consumption. Developmental toxicity was evidenced by a significant decrease in fetal weight per litter and an increase in the total number of fetuses and litters showing bone retardation. No beneficial effects of deferiprone on these adverse effects could be observed. By contrast, a more pronounced decrease in maternal weight gain and corrected body weight change, as well as a higher number of litters with fetuses showing skeletal variations was noted in the group exposed to Al nitrate and treated with deferiprone at 24 mg/kg. According to the current results, deferiprone would not be effective to prevent Al-induced maternal and embryo/fetal toxicity in mice.

Embryotoxic effects of methylmercuric chloride administered to mice and rats during orangogenesis.

Pregnant C57BL mice were given a daily dose of 7.5, 6.0, 5.0 or 2.5 mg/kg methylmercuric chloride (MMC) orally from the sixth through the thirteenth day of pregnancy. Pregnant Wistar rats were given a daily dose of 7.5, 5.0 or 2.5 mg/kg MMC orally from the seventh through the fourteenth day of pregnancy. Fetal examinations were performed on days 18 and 20 in mice and rats, respectively. In mice, the dose of 7.5 mg/kg was embryocidal. The dose of 6.0 mg/kg also caused a high incidence of fetal death, decreased fetal weight and a marked increase in malformations. A dose of 5.0 mg/kg caused a decrease in fetal weight and a marked increase in the incidence of malformations. The most common malformations were cleft palate and fused thoracic vertebrae. In rats, the dose of 7.5 mg/kg caused a high incidence of fetal death and malformations. The most frequent malformations were cleft palate, generalized edema, brain lesions and wavy ribs. A dose of 5.0 mg/kg caused a significant decrease in fetal weight and a significant increase in the incidence of malformations.

Teratologic evaluation of synthetic delta-9-tetrahydrocannabinol in rats.

Delta-9-Tetrahydrocannabinol (THC) was dissolved in propylene glycol and 25, 50, or 100 mg/kg administereed dialy sc to pregnant Charles River Sprague-Dawley rats on days 6-15 of gestation (presence of sperm considered day 1). Maternal weight gain was depressed, but a significant decrease in fetal weight occurred only in the 50 mg/kg group. No malformations were noted, only some abnormalities consisting of several instances of rudimentary 14th rib and soft or spongy spinal cords.

EFFECT OF SODIUM TOLBUTAMIDE ON PREGNANT ALBINO RATS AND THEIR YOUNG.

The sodium salt of tolbutamide, in dosages ranging from 12.5 mg./kg. to 125 mg./kg. body weight, was administered to pregnant albino rats to determine its effect upon litter size, individual fetal weight, normal development of the young, and the fetal skeleton. As the dosage level increased, a statistically significant decrease in fetal weight was observed. Tolbutamide administration had no detrimental effect upon the total number of implantations; however, a large number of resorptions occurred at the 125 mg./kg. level resulting in a decreased litter number. The number of rats having litters with fetuses weighing less than three grams increased as the dosage increased from 12.5 mg./kg. to 100 mg./kg. levels. No adverse effect on the maternal animal was noted except at the 100 mg./kg. and 125 mg./kg. levels. At these levels all animals experienced a localized tetanic response which varied in duration according to the level of injection. The number of sternebrae, metacarpals, and metatarsals, as well as long bones, indicated that the number and size of bones varied inversely with increased dosage levels. Normal skeletal development occurred despite dosages up to and including the 37.5 mg./kg. level. Abnormalities were observed from the 50 mg./kg. to the 125 mg./kg. level of administration.