Number Of Fetal Resorptions Research Articles

Attenuating effects of selenium and zinc against hexavalent chromium-induced oxidative stress, hormonal instability, and placenta damage in preimplanted rats.

As a toxic metal, hexavalent chromium (CrVI) has effects on both the reproductive and endocrine systems. This study aimed to evaluate the protective effects of selenium (Se) and zinc (Zn) against the toxicity of chromium on the placenta in pregnant Wistar albino rats. Thirty pregnant Wistar rats were divided into control and four treated groups, receiving subcutaneously (s.c) on the 3rd day of pregnancy, K2Cr2O7 (10mg/kg body weight (bw)) alone, or in association with Se (0.3mg/kg bw), ZnCl2 (20mg/kg bw), or both of them simultaneously. Plasma steroid hormones, placenta histoarchitecture, oxidative stress profile, and developmental parameters were investigated. These results showed that K2Cr2O7 exposure induced a significant increase in the levels of both plasma estradiol (E2) and placenta malondialdehyde (MDA), the number of fetal resorptions, and percent of post-implantation loss. On the other hand, K2Cr2O7 significantly reduced developmental parameters, maternal body and placenta weight, and plasma progesterone (P) and chorionic gonadotropin hormone (β HCG) levels. However, K2Cr2O7 significantly decreased the placenta activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH), and nonprotein sulfhydryl (NPSH). These changes have been reinforced by histopathological evaluation of the placenta. Se and/or ZnCl2 supplementation provoked a significant improvement in most indices. These results suggest that the co-treatment with Se or ZnCl2 strongly opposes the placenta cytotoxicity induced by K2Cr2O7 through its antioxidant action.

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.

Preventive effects of folic acid on Zika virus-associated poor pregnancy outcomes in immunocompromised mice.

Zika virus (ZIKV) infection may lead to congenital microcephaly and pregnancy loss in pregnant women. In the context of pregnancy, folic acid (FA) supplementation may reduce the risk of abnormal pregnancy outcomes. Intriguingly, FA may have a beneficial effect on the adverse pregnancy outcomes associated with ZIKV infection. Here, we show that FA inhibits ZIKV replication in human umbilical vein endothelial cells (HUVECs) and a cell culture model of blood-placental barrier (BPB). The inhibitory effect of FA against ZIKV infection is associated with FRα-AMPK signaling. Furthermore, treatment with FA reduces pathological features in the placenta, number of fetal resorptions, and stillbirths in two mouse models of in utero ZIKV transmission. Mice with FA treatment showed lower viral burden and better prognostic profiles in the placenta including reduced inflammatory response, and enhanced integrity of BPB. Overall, our findings suggest the preventive role of FA supplementation in ZIKV-associated abnormal pregnancy and warrant nutritional surveillance to evaluate maternal FA status in areas with active ZIKV transmission.

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Objectives Research on the pathogenesis and treatment of preeclampsia is hindered by lack of animal models. Here, we tested the hypothesis that the Dahl Salt Sensitive (Dahl S) rat, a known model of hypertension and kidney disease, is also a spontaneous model of preeclampsia. Methods We compared pregnancy in the Dahl S to a normotensive control rat strain, Sprague Dawley (SD), and another model of genetic hypertension with normal cardiovascular adaptations to pregnancy, the Spontaneously Hypertensive Rat (SHR). Female rats were implanted with telemetry units (DSI) via the femoral artery, allowed to recover for 10 days, and then mated with males of their same strain. Uterine artery resistance index (UARI) was measured on gestational day (GD) 18 via Doppler ultrasound (Vevo770) in anesthetized animals (n = 5–12), and urine was collected via metabolic cage on GD19. Rats were euthanized on GD20, pups were measured, the number of fetal resorptions was noted, and placentas were harvested for further analysis. Results Mean arterial pressure (MAP), proteinuria, and UARI were significantly greater at late pregnancy in the Dahl S rat compared to SD and SHR (Table). In the control strains, MAP decreased during pregnancy as expected, but there was a rise in MAP in the Dahl S. Pup and litter sizes were significantly smaller in the Dahl S rat, with an increased number of fetal resorptions in the Dahl S rat, indicating intrauterine growth restriction is present in this strain (Table). Conclusions These data suggest that the Dahl S rat exhibits a superimposed preeclamptic phenotype during pregnancy that is distinctive from preexisting hypertension during pregnancy as seen in the SHR control. Strain MAP (mmHg) Δ MAP (mmHg) Proteinuria (g/day) UARI # of Pups per Litter Pup weight/maternal weight (g/kg) Percent fetal resorptions SD 94 ± 2.2 −10.9 ± 2.1 11.0 ± 5.9 0.50 ± 0.01 13.3 ± 1.9 10.9 ± 0.3 0 SHR 114 ± 10.7∗ −20.3 ± 10.5 4.2 ± 3.2 0.53 ± 0.04 11.2 ± 0.6 8.3 ± 0.3 0 Dahl S 166 ± 3.0∗# 8.6 ± 2.4∗# 253.7 ± 28.2∗# 0.71 ± 0.02∗# 6.5 ± 1.6∗ 6.7 ± 0.8∗ 17.1 ± 6.5∗# ∗p Disclosures E.E. Gillis: None. J.N. Mooney: None. M.R. Garrett: None. J.M. Sasser: None.

Adverse effects of rosemary (Rosmarinus officinalis L.) on reproductive function in adult male rats.

Ingestion of rosemary (Rosmarinus officinalis L.) by two groups of adult Sprague-Dawley rats at levels of 250 and 500 mg/kg body wt for 63 days was investigated for its effects on fertility. Body weight and absolute and relative testes weights were not affected, but the average weights of epididymides, ventral prostates, seminal vesicles, and preputial glands decreased significantly. A significant decline in spermatogenesis in testes due to a decrease in the number of primary and secondary spermatocytes and spermatids in treatment group 2 (500 mg/kg) is attributed to a significant decrease in testosterone. Sperm motility and density were also significantly decreased in the cauda epididymis and in the testes of rosemary-treated male rats in group 2. In addition, the treatment markedly increased the number of fetal resorptions in female rats impregnated by group 2 males, thereby reducing their fertility.

Pregnancy outcomes following pre- and post-implantation exposure of Sprague–Dawley rats to benzyl isothiocyanate

The present investigation examines the outcomes of rats' pregnancy following pre- and post-implantation maternal exposure (orally) to benzyl isothiocyanate (BITC; 12.5, 25 and 50 mg/kg body weight). Three maternal deaths were recorded in the group of rats treated with 50 mg/kg BITC. Obvious signs of toxicity characterized by hypo-activity, perinasal staining, piloerection, hunched posture and decrease in body weights were observed in BITC-treated rats during the treatment periods. Dose-dependent increase in early fetal resorptions was seen in rats treated with BITC prior to implantation, but was not statistically significant. There were no significant differences in the number of implantation sites in treatment groups compared with the control. Similarly, there were no significant differences in the number of fetal resorptions, relative weights of maternal liver, kidney and spleen of rats in post-implantation treatment groups compared with the control. The differences in the number of viable fetuses in treatment groups compared with the control were also not significant. However, fetal weights in rats treated with 25 and 50 mg/kg BITC and placental weights in all the treatment groups were significantly lower than the control. In conclusion, at 12.5–50 mg/kg, BITC did not cause significant pre- and post-implantation fetal loss in pregnant rats. BITC-induced low fetal and placental weights could be of obstetrical importance, but at levels/doses that would provoke maternal toxicity.

Effect of antenatal exposure to paroxetine (paxil) on growth and physical maturation of mice offspring.

Our purpose was to determine, in a placebo-controlled manner, whether antenatal exposure to paroxetine affected long-term growth and physical maturation of mice offspring. Forty-one CD-1 mice consumed paroxetine (n = 21) or a placebo (n = 20) for 2 weeks before conception and throughout gestation. The daily dose of paroxetine (Paxil; 30 mg/kg/d) was known to achieve concentrations in the serum equivalent to the upper therapeutic level in humans and in the fetal brain equivalent to that of the adult mouse. Growth and physical maturation of the offspring were compared by paired t-test, Welch's corrected test, and Fisher's exact test. The maternal weight gain, litter sizes, number of fetal resorptions, and gestational age at delivery were not different between the paroxetine and the placebo-exposed offspring. Newborn pups exposed to paroxetine were more likely to have low birthweights (1.65 gm vs. 1.70 gm; P < 0.05) and narrower heads (7.7 mm vs. 8.1 mm; P < 0.05). Body weight, body length, and head circumference measurements increased in a manner that was indistinguishable between the two groups of offspring, regardless of gender. No differences in achievement of physical milestones (lower incisor eruption, eye opening, and development of external genitalia) were noted between the two groups. The reproductive capability and the perinatal outcomes of the second-generation offspring were unaffected by paroxetine exposure. A clinically relevant dose of paroxetine, when given throughout gestation, did not affect long-term growth and physical maturation of mice offspring.

Effect of Antenatal Exposure to Paroxetine (Paxil) on Growth and Physical Maturation of Mice Offspring

Objective: Our purpose was to determine, in a placebo-controlled manner, whether antenatal exposure to paroxetine affected long-term growth and physical maturation of mice offspring.Methods: Forty-one CD-I mice consumed paroxetine (n = 21) or a placebo (n = 20) for 2 weeks before conception and throughout gestation. The daily dose of paroxetine (Paxil; 30 mg/kg/d) was known to achieve concentrations in the serum equivalent to the upper therapeutic level in humans and in the fetal brain equivalent to that of the adult mouse. Growth and physical maturation of the offspring were compared by paired t-test, Welch's corrected test, and Fisher's exact test.Results: The maternal weight gain, litter sizes, number of fetal resorptions, and gestational age at delivery were not different between the paroxetine and the placebo-exposed offspring. Newborn pups exposed to paroxetine were more likely to have low birthweights (1.65 gm vs. 1.70 gm; P < 0.05) and narrower heads (7.7 mm vs. 8.1 mm; P < 0.05). Body weight, body length, and head circumference measurements increased in a manner that was indistinguishable between the two groups of offspring, regardless of gender. No differences in achievement of physical milestones (lower incisor eruption, eye opening, and development of external genitalia) were noted between the two groups. The reproductive capability and the perinatal outcomes of the second-generation offspring were unaffected by paroxetine exposure.Conclusion: A clinically relevant dose of paroxetine, when given throughout gestation, did not affect long-term growth and physical maturation of mice offspring.

Placental thrombosis and fetal loss after passive transfer of mouse lupus monoclonal or human polyclonal anti-cardiolipin antibodies in pregnant naive BALB/c mice.

In the present study we evaluated the effect of passive transfer of a mouse monoclonal (CAM) or a human polyclonal anti-cardiolipin IgG on pregnancy outcome in BALB/c mice. The mice were immunized through the tail vein immediately after mating with 10 micrograms of monoclonal or polyclonal anti-cardiolipin antibodies. Two other groups of mice were given a mouse irrelevant monoclonal antibody or normal human polyclonal IgG respectively, at the same dose. In mice immunized with monoclonal or polyclonal anti-cardiolipin antibody we observed a significant increase in the number of fetal resorptions and a significant reduction of the mean weights of the embryos and the placentas. In mice immunized with CAM we also found a significant decrease in the number of healthy pups, while mice infused with human aCL antibody expressed a significant reduction in the fecundity rate. The histological examination showed widespread thrombosis and necrosis in the placentas derived from the mice immunized with the anti-cardiolipin antibodies. The model supports a possible direct pathogenetic effect of anti-phospholipid antibodies in recurrent fetal loss and points out that thrombotic events at placental level can be instrumental in the pathogenesis of the obstetric complications.

Effect of regular voluntary exercise on resting cardiovascular responses in SHR and WKY pregnant rats.

The purpose of this study was to assess the influence of regular voluntary exercise in pregnant normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats on 1) uteroplacental perfusion and mean arterial pressure in the resting conscious condition and 2) fetal number, fetal weight, and number of fetal resorptions. WKYs and SHRs were randomly assigned to standard cages [CWKY (n = 10); CSHR (n = 6)] or cages with activity wheels [EWKY (n = 7); ESHR (n = 8)]. EWKYs and ESHRs exercised for 12 wk, and then all rats were bred and experiments were conducted on gestational day 17. Resting blood flow (microspheres), heart rate (HR), and mean arterial pressure (Pa) were measured. No significant difference was found in Pa, HR, uterine blood flow (ESHRs 52 +/- 8 ml.min-1.100 g-1; CSHRs 28 +/- 6 ml.min-1.100 g-1), or maternal placental blood flow (ESHRs, 122 +/- 31 ml.min-1.100 g-1; CSHRs 78 +/- 21 ml.min-1.100 g-1) among the groups. Exercise altered the relationship between maternal placental and uterine blood flow and Pa in the SHR; SHRs with lower Pa maintained higher placental and uterine blood flow after training. Before gestation ESHRs ran on average more kilometers per week than EWKYs (43 +/- 3 vs. 34 +/- 4), but during gestation ESHRs averaged fewer kilometers per week than EWKYs (16 +/- 4 vs. 22 +/- 4). Succinate dehydrogenase activity was higher in the white vastus lateralis (1.02 +/- 0.2 mumol cytochrome c reduced.min-1.g wet wt-1) and vastus intermedius (3.1 +/- 0.5 mumol cytochrome c reduced.min-1.g wet wt-1) muscles of ESHRs.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of in Utero Ultrasound Exposure on the Development of the Fetal Mouse Testis1

The effect on the developing fetal testis of in utero exposure to 1-MHz, continuous-wave ultrasound in the spatial peak, temporal average intensity range 0.5-10 W/cm2 for durations of 400-30 sec on Day 9, 12, or 15 of gestation was determined. Results show that two subtle, yet potentially deleterious, effects occurred: a reduction in the Sertoli cell population and an apparent delay in the cessation of gonocyte mitosis. An increase was also seen in the number of fetal resorptions and stillborn pups per number of implantation sites in the exposed specimens as compared to the sham and cage controls. Because the reduction in testis weight was proportional to decreased body weight and because there was no difference in Sertoli cell numbers due to day of treatment, the testicular effects may reflect a generalized delay in growth. Whether this effect of ultrasound on fetal testis will be translated into an equal reduction in germ cell numbers in the adult testis remains to be determined.

Developmental toxicity of Clarified Slurry Oil applied dermally to rats.

Clarified Slurry Oil (CSO), the heavy residual fraction from the fluidized catalytic cracker, was applied to the shaven backs of groups of 10 pregnant rats at doses of 0, 4, 8, 30, 125, and 250 mg/kg/day. All groups received the test material on gestation days 0-19. CSO was applied undiluted and left uncovered on the skin; collars were placed on the rats to minimize ingestion of the test material. Signs of maternal toxicity, some of which were seen at dose levels as low as 8 mg/kg/day, included vaginal bleeding, decreased body weight gain, reduced food consumption, death, increased relative liver weights, atrophy of the thymus, and aberrant serum chemistry. The number of fetal resorptions/deaths was markedly increased and the number of viable offspring decreased by CSO at dosages of 30 mg/kg/day and above. The group receiving 250 mg/kg/day carried no viable offspring. Fetuses from pregnant females exposed to CSO at dose levels in excess of 8 mg/kg/day were smaller than those from control and 4 mg/kg/day groups, and their skeletons showed decreased ossification. Abnormal external development and visceral development were observed in living and dead fetuses exposed in utero to CSO at dose levels as low as 8 mg/kg/day. Based on these data, 4 mg/kg/day represents the No-Observed-Adverse-Effect-Level for both maternal and developmental toxicity.

Dose requirements, assay procedures and tissue specificity for PCB inductation of P-450 dependent mono-oxygenase activity in the rat: implications for design of studies measuring in vivo induction of human placental mono-oxygenases.

Pregnant Sprague-Dawley and Fisher 344 rats were treated on day 15 of gestation with Aroclor 1254 in a single dose ranging from 0 to 500 mg kg-1 body weight and killed on day 18 of gestation. In the small groups of animals used for this study, no effect was observed on mean maternal liver or placental weight, or the number of fetal resorptions at any of the doses tested. Measurement of aryl hydrocarbon hydroxylase (AHH) and 7-ethoxycoumarin O-deethylase (7ECD) activity in tissue homogenates, however, showed that administration of Aroclor 1254 (15 mg kg-1 body weight or greater) induced mono-oxygenase activity in fetal liver. Both the AHH and 7ECD assay detected effects of PCBs with similar sensitivity, and the findings were comparable when homogenates were assayed instead of microsomes. These data were used to suggest technical approaches to the detection of mono-oxygenase induction in placental tissue human populations exposed to PCBs.

Influence of exercise training on maternal and fetal morphological characteristics in the rat.

Evidence in both humans and animals has shown that exercise before or during pregnancy may effect fetal outcome. The purpose of this investigation was to examine the effects of an exercise program on fetal development in the rat. Prior to impregnation one group of animals was exercise-trained on a Quinton shock-stimulus rodent treadmill. The exercised group was trained to run 5 days/wk, for 2.0 h/day at 31 m/min up an 8 degree incline for 8 wk before mating. Following mating the training intensity was reduced to 27 m/min up a 5 degree incline, and the exercise period decreased to 1 h/day. On day 19 of gestation, 24 h postexercise for the trained mothers, the animals were killed in the fed state and the maternal and fetal characteristics were measured. The sedentary controls gained significantly (P less than 0.05) more body weight during pregnancy. This can be attributed to three factors: higher number of fetuses, 14.83 +/- 0.04 vs. 12.2 +/- 0.85 for the trained; larger litter weights, 44.25 +/- 4.97 vs. 26.17 +/- 1.82 g/dam for the trained; and slightly larger lipid stores. In addition to having fewer pups the trained mothers had a greater number of fetal resorptions; 0.9/dam as opposed to 0.17/dam for the sedentary control. Analysis of fetal body composition showed no difference in total body water, protein, or fat between the pups of sedentary and trained dams. The results of this study indicate that exercise training prior to and during pregnancy influences fetal development in the rat.