Postimplantation Loss Research Articles

Toxicological Study of Sodium Selenite on Fetal Development and DNA Fragmentation in Liver Cells of Pregnant Rats

The present study was carried out to evaluate the effects of sodium selenite on fetal development and DNA in liver of rats. Pregnant rats were divided into three groups: control group, group treated orally with 5µg Se/kg body wt. and group treated orally with 10µg Se/kg body wt. Dams were treated orally with sodium selenite from day 7 to 19 of gestation. Sodium selenite treatment revealed decrease in maternal body weight, reduction in fetal weight, length and number of viable fetuses, increased number of resorbed fetuses and post-implantation loss at the two doses tested. Fetal skeleton showed signs of developmental delay in skull and limbs of the treated groups. Sodium selenite treatment revealed significant reduction of placental and liver weights in treated dams. Sodium selenite-induced oxidative stress in liver tissue of rats as evidenced by increase in lipid peroxidation and glutathione peroxidase activity, while catalase was significantly decreased. Also, increase in DNA fragmentation, marked reduction of hepatic DNA content, and many histopathological changes in the liver were recorded. The results demonstrated that treatment of pregnant rats with sodium selenite at the toxic dosages chosen showed maternal and fetal toxicity that may be concerned with hepatic oxidative stress accompanied with DNA fragmentation and depletion of total DNA content.

Effects of Ginkgo biloba extract on the embryo‐fetal development in Wistar rats

Ginkgo biloba extract (GBE) is an herbal medicine used for treating neurodegenerative diseases, cerebrovascular insufficiency, peripheral arterial occlusive disease, and also vestibular disturbance. Some components of GBE have presented estrogenic effects and, in a previous study, high dosages of GBE caused intra-uterine growth retardation in fetuses of Wistar rats treated during the fetogenesis period. Pregnant Wistar rats were treated, through gavage, with different dosages of aqueous GBE (3.5, 7.0, and 14.0 mg/Kg/day), during the tubal transit and implantation period. Rats were killed on the 15th day of pregnancy and the following parameters were evaluated: clinical symptoms of maternal toxicity; maternal body weight; feed and water intake; maternal liver, kidney, and ovary weights; number of corpora lutea; implants per group ratio; pre- and post-implantation loss per group ratio; live fetuses mean; dead fetuses percentage; fetus and placenta weight per offspring ratio; and fetal external malformation. No significant alteration was found for both the maternal and embryonic parameters evaluated. The GBE treatment in pregnant Wistar rats, during the tubal transit and implantation period, caused no toxic effect on the maternal organism and did not induce embryonic death, growth retardation, and/or fetal malformations.

Reproductive and Developmental Toxicity of Amitraz in Sprague-Dawley Rats

The present study was conducted to obtain information on the effects of amitraz on reproductive and developmental parameters in rats. The test chemical was administered via the drinking water containing 0, 40, 120, and 360 ppm to male rats from 2 weeks before mating to the end of 14-day mating period and to females from 2 weeks before mating, throughout mating, gestation and up to lactational day 4. During the study period, clinical signs, body weights, food intake, organ weights, reproductive and littering findings, necropsy findings, sperm parameters, and histopathology were examined. At 360 ppm, decreases in the body weight gain, food consumption, and the number of live pups and an increase in the post-implantation loss were observed. In addition, decreases in the seminal vesicle weight and sperm motility were found in males. At 120 ppm, a decrease in the food consumption was found transiently in both males and females, but no reproductive and developmental toxicity was observed in both sexes. There were no signs of either general or reproductive and developmental toxicity in the 40 ppm group. Based on these results, it was concluded that the repeated oral administration of amitraz to rats resulted in a decrease in the food consumption at 120 ppm and decreases in the seminal vesicle weight, sperm motility, and the number of live pups and an increase in the post-implantation loss at 360 ppm in rats. Under these experimental conditions, the no-observed-adverse-effect level (NOAEL) of amitraz for general and reproduction/developmental toxicity was believed to be 120 ppm, and the no-observed-effect level (NOEL) of amitraz was believed to be 40 ppm in rats.

Reversibility of the effects of the chemotherapeutic regimen for non-Hodgkin lymphoma, cyclophosphamide, doxorubicin, vincristine, and prednisone, on the male rat reproductive system and progeny outcome

The chemotherapeutic agents used to treat non-Hodgkin lymphoma, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), have adverse effects on male reproductive function and progeny outcome. To determine the reversibility of these effects, male rats received a CHOP treatment mimicking human exposure. CHOP reduced testicular and epididymal weights; these remained decreased after 9 weeks recovery. This treatment also decreased testicular sperm number and increased spermatozoal DNA damage. Although sperm production returned to control values after 9 weeks recovery, DNA damage persisted. Decreased litter size, and increased pre- and post-implantation losses were observed among litters sired by CHOP-exposed males. Litter size and pre-implantation loss returned to control within 3 weeks post-treatment and post-implantation loss by 6 weeks. Thus, effects of CHOP on progeny outcome were reversed 9 weeks post-treatment, although germ cell DNA breaks remained elevated. These data suggest that the ability to sire viable progeny may not be a sensitive measure of spermatozoal quality in rats.

Disrupted imprinting status at the H19 differentially methylated region is associated with the resorbed embryo phenotype in rats

Igf2, an imprinted gene that is paternally expressed in embryos, encodes an embryonic growth factor. An important regulator of Igf2 expression is methylation of the H19 differentially methylated region (DMR). A significant association has been observed between sperm methylation status at the H19 DMR and post-implantation loss. In addition, tamoxifen treatment has been shown to increase post-implantation loss and reduce DNA methylation at the H19 DMR in rat spermatozoa. Because this DMR is a primary DMR transmitting epigenetic imprint information from the gametes to the embryo, the aim of the present study was to determine the imprinting status of H19 DMR in post-implantation normal and resorbed embryos (F(1)) and to compare it with the H19 DMR in the spermatozoa of the respective sires. Analysis of the H19 DMR revealed methylation errors in resorbed embryo that were also observed in their sires' spermatozoa in the control and tamoxifen-treated groups. Expression analysis of the reciprocally imprinted genes Igf2 and H19 showed significant downregulation of Igf2 protein without any effect on H19 transcript levels in the resorbed embryos. The results indicate an association between disrupted imprinting status at the H19 DMR in resorbed embryos and the spermatozoa from their respective sires regardless of treatment, implying a common mechanism of resorption. The results demonstrate transmission of methylation errors at the Igf2-H19 locus through the paternal germline to the subsequent generation, emphasising the role of paternal factors during embryogenesis.

Delayed ossification in Wistar rats induced by Morinda citrifolia L. exposure during pregnancy

Different products of plant Morinda citrifolia L. (noni) have been marketed and used around the world based on properties described by Polynesian people that use them for more than 2000 years. Marketing of these products is based on their presumptive phytotherapic properties. However there is little scientific evidence about their safety, especially when used during pregnancy. Aim of the study Evaluate the possible developmental toxicity of the noni fruit aqueous extract and commercial product of TAHITIAN NONI ® juice in rats exposed during pregnancy. Materials and methods Pregnant Wistar rats were exposed by gavage to 7, 30 and 300 mg/kg bw (body weight) of noni aqueous extract or to 0.4, 2 and 20 mL/kg bw (body weight) of noni juice between day 7 and day15 of pregnancy. Caesarean sections were performed on day 20 of pregnancy and reproductive parameters were evaluated. Implantations sites and postimplantation losses were recorded. Fetuses were weighted and examined for externally visible anomalies. After, the fetuses were cleared with KOH and the bones stained with alizarin red. Skeletal alterations of the skull, vertebral column, ribs, forelimbs, hindlimbs, sternum, sings of delayed ossification and variations were examined in accordance with pre-defined criteria and identified using harmonized and internationally accepted nomenclature recommended by the International Federation of Teratology Societies. Results Exposure with extract and juice of Morinda citrifolia did not induce maternal toxicity at the tested doses, but induced delayed ossification in fetuses. Conclusion The exposure of pregnant rats to aqueous extract or juice Morinda citrifolia during organogenesis period may induce adverse effects on the normal development of fetuses. These findings indicate the need for further studies with noni derivates preceding their use in pregnant women.

Inter‐laboratory control data for reproductive endpoints required in the OPPTS 870.3800/OECD 416 reproduction and fertility test

The U.S. EPA revised the Reproduction and Fertility Effects Test Guideline (OPPTS 870.3800/OECD 416) in 1998, adding numerous endpoints in an effort to incorporate new methodologies, improve the sensitivity for detecting reproductive toxicants, and more efficiently utilize study animals. Many of these new endpoints have not been used in regulatory reproductive toxicology studies prior to their inclusion in the test guidelines; thus, the Health and Environmental Sciences Institute (HESI) of the International Life Sciences Institute (ILSI) initiated the Reproductive Endpoints Project to examine the utility of these new endpoints. This report provides a retrospective analysis of 43 multi-generation studies (16 in Wistar rats, 27 in Sprague-Dawley rats) conducted according to the latest version of the test guidelines. It focuses on vehicle (negative) control values (means and ranges) for the various endpoints to examine inter-laboratory variability. Based on the compiled data, the most variable endpoints across laboratories and their associated coefficients of variation (CV) for each generation were: percent abnormal sperm (166-205%), testicular spermatid concentration (126-147%), postimplantation loss (97-104%), primordial follicle counts (69%, only measured in P2 females), and epididymal sperm concentration (52-57%). Absolute and relative prostate and thymus weights, weanling uterine weights, and anogenital distance had CVs of 25-50%. Sources of variability included procedural differences between laboratories, inherent biological variability, and/or small sample sizes for some endpoints. These inter-laboratory control data provide a means for laboratories to review their performance on reproductive toxicity measures, and provide perspective for interpreting their own control data and data from treated animals.

Effects of Concrete and Wood Building Environments on Pregnant Dams and Embryo-Fetal Development in Rats.

We have recently reported that the continuous exposure of rats to a concrete building environment under cool temperatures had adverse effects on general health parameters and embryo-fetal development. This study examined to compare the potential effects of concrete and wood building environments on pregnant dams and embryo-fetal development in rats. Groups of 10 mated females were exposed to polycarbonate (control), concrete, or wood cages from gestational days (GD) 0 to 20 under cool temperatures (11.9∼12.3°C). All the females underwent a caesarean section on GD 20, and their fetuses were examined for any morphological abnormalities. The temperatures in the cages were similar in all groups but the relative humidity in the concrete and wood groups were higher than in the control group. The concentration of volatile organic compounds in the wood group was higher than in the control group. In the concrete group, maternal effects manifested as an increase in the incidence of clinical signs, a lower body weight, and a decrease in the thymus and ovary weights. Developmental effects included increased post-implantation loss and decreased litter size. Infrared thermal analysis showed that the skin temperature of the rats in the concrete group was lower than that in the control group. In contrast, there were no exposure-related adverse effects on the maternal and developmental parameters in the wood group. Overall, the exposure of pregnant rats to a concrete building environment under cool temperatures has adverse effects on the clinical signs, body weight, skin temperature, organ weight, and embryo-fetal development. On the other hand, exposure to a wood building environment does not have any adverse effects in rats.

Effects of Sri Lankan Black Tea (Camellia sinensis L.) on Pregnancy of Rats

The aim of this study was to demonstrate the potential effects of black tea brew of Camellia sinensis using Sri Lankan high grown dust grade no. 1 tea on pregnancy outcome of rats when exposed during early (days 1-7), mid (days 8-14) and late (days 15-21) pregnancy of rats. Different doses of black tea brew (mg/ml/day) was orally administered daily during this period to separate groups of rats (n = 6/group): 84 (equivalent to 1.5 cups), 167 (3 cups), 501 (9 cups), and 1336 (24 cups). The results showed that black tea brew did not significantly (P > 0.05) change the pregnancy outcome (in terms of quantal pregnancy, number of uterine implants, number of viable implants, implantation index, pre-implantation loss, post-implantation loss, gestation index, number of pups born, litter index, live birth index and viability index) and pre- (in terms of length of the implants/foetus, gestation length, cranial length, cranial diameter and tail length of pups) and postnatal (in terms of time taken to open eyes, eruption of incisors and appearance of fur) development. Furthermore, black tea brew did not induce gross morphological birth abnormalities. If the results are applicable to women, it is concluded that even heavy consumption of black tea brew during pregnancy may not be harmful for pregnancy outcome.

Animal models for clinical and gestational diabetes: maternal and fetal outcomes

BackgroundDiabetes in pregnant women is associated with an increased risk of maternal and neonatal morbidity and remains a significant medical challenge. Diabetes during pregnancy may be divided into clinical diabetes and gestational diabetes. Experimental models are developed with the purpose of enhancing understanding of the pathophysiological mechanisms of diseases that affect humans. With regard to diabetes in pregnancy, experimental findings from models will lead to the development of treatment strategies to maintain a normal metabolic intrauterine milieu, improving perinatal development by preventing fetal growth restriction or macrosomia. Based on animal models of diabetes during pregnancy previously reported in the medical literature, the present study aimed to compare the impact of streptozotocin-induced severe (glycemia >300 mg/dl) and mild diabetes (glycemia between 120 and 300 mg/dl) on glycemia and maternal reproductive and fetal outcomes of Wistar rats to evaluate whether the animal model reproduces the maternal and perinatal results of clinical and gestational diabetes in humans.MethodsOn day 5 of life, 96 female Wistar rats were assigned to three experimental groups: control (n = 16), severe (n = 50) and mild diabetes (n = 30). At day 90 of life, rats were mated. On day 21 of pregnancy, rats were killed and their uterine horns were exposed to count implantation and fetus numbers to determine pre- and post-implantation loss rates. The fetuses were classified according to their birth weight.ResultsSevere and mild diabetic dams showed different glycemic responses during pregnancy, impairing fetal glycemia and weight, confirming that maternal glycemia is directly associated with fetal development. Newborns from severe diabetic mothers presented growth restriction, but mild diabetic mothers were not associated with an increased rate of macrosomic fetuses.ConclusionExperimental models of severe diabetes during pregnancy reproduced maternal and fetal outcomes of pregnant women presenting uncontrolled clinical diabetes. On the other hand, the mild diabetes model caused mild hyperglycemia during pregnancy, although it was not enough to reproduce the increased rate of macrosomic fetuses seen in women with gestational diabetes.

Perinatal exposure of rats to Bisphenol A affects the fertility of male offspring

Aims The exposure to endocrine disruptor (ED) induces functional and behavioral abnormalities associated with reproduction. Humans are ubiquitously exposed to Bisphenol A (BPA), an ED, as it leaches from polycarbonate plastics into their contents. The aim of the present study was to determine the effect of perinatal exposure of male rats to BPA on fertility parameters and perturbations in the expression of testicular steroid receptors (SRs) in adult F 1 offspring. These effects were studied in adult males of the F 2 and F 3 generations to determine the vertical transmission of BPA exposure. Main methods Pregnant female rats (F 0) were gavaged with either BPA (1.2 and 2.4 μg/kg bw), a vehicle control or positive control with Diethylstilbestrol (10 μg/kg bw) during the perinatal period. Adult F 1 males were subjected to fertility assessment by mating with unexposed females. The reproductive functions of the subsequent F 2 and F 3 litters were investigated in a similar manner. Immunohistochemical localization of SRs was carried out in the testes of F 1, F 2 and F 3 generation adult rats. Key findings A significant increase in post implantation loss and a decrease in litter size and sperm count and motility were observed in the F 1 male offspring. A reduction in the testicular expression profile of SRs was observed. These effects were very prominent in the subsequent F 2 and F 3 generations. Significance Perinatal exposure to environmentally relevant doses of BPA affects the male germ line, leading to impairments in the fertility of F 1 male offspring and their subsequent F 2 and F 3 generations.

Neonatal exposure of male rats to Bisphenol A impairs fertility and expression of sertoli cell junctional proteins in the testis

Background Sertoli cell junctional proteins (SCJP) (viz. adhesion, gap and tight junctions) are important for spermatogenesis and perturbations in expression of these proteins are associated with impairments in process of sperm production. Bisphenol A (BPA) is an endocrine disrupter that has been associated with impaired spermatogenesis. However the mechanistic basis of impaired spermatogenesis is unknown, whether BPA is a Sertoli cell toxicant has not yet been fully investigated. Objectives The present study was undertaken to decipher the effects of neonatal exposure of male rats to BPA on fertility and its effect on the testicular expression of SCJP during development. Methods Neonatal male rats were s.c. injected with BPA at doses ranging from 0.6 to 10 μg/rat (100–1600 μg/kg bw of BPA) on post-natal days (PNDs) 1–5, and controls received vehicle. Diethylstilbestrol (DES) was used as a positive control. Male fertility was assessed during adulthood and the lowest dose of BPA that was most effective at impairing fertility was determined. Immunohistochemical localization for Connexin 43 (Cx-43, gap junctional), Zona Occludin-1 (ZO-1, tight junctions) and N-cadherin (adherens junction) was carried out on testicular tissue sections obtained from PNDs 15, 30, 45 and 90 of rats exposed to lowest dose of BPA that impaired fertility. Results Females mated with male rats that were exposed neonatally to various concentrations of BPA showed a significant increase in post-implantation loss and a decrease in litter size. There were significant changes in sperm count along with hormonal imbalances in the rats exposed neonatally to BPA. The 2.4 μg dose (400 μg/kg bw) of BPA was determined as the lowest dose that was capable of impairing male fertility. A significant reduction in the expression of Cx-43 (PND 45 and 90) and increases in the expression of N-cadherin (PND 45 and 90) and ZO-1 (PND 90) were observed in the testes of rats exposed neonatally to effective dose of BPA. Interestingly, there was an altered expression pattern of Cx43 amongst the sloughed cells in the testes of the experimental rats as compared to controls. Conclusion Neonatal exposure of BPA to rats impairs their fertility and has the potential to induce perturbations in SCJP. These perturbations may be one of the contributing factors that lead to impairments in spermatogenesis in the exposed animals and can be used as potential biomarkers to study BPA-induced effects on testes.

Induction of dominant lethal mutations by Ascaris trypsin inhibitor in male mice

Trypsin inhibitor (ATI) isolated from Ascaris suum, a gastrointestinal nematode parasite, was tested for the induction of dominant lethal mutations in male mice. Dominant lethal effects of ATI for the main stages of germ cell development were analyzed by mating at specific time points after dosing. Three groups of adult BALB/c males received 50, 100 or 250 mg/kg body weight (bw) single intraperitoneal (ip) injection of ATI in sterile phosphate-buffered saline (PBS). The control group received concurrent injection of PBS. After the administration of ATI or PBS, each male was mated with two untreated females. For fractionated examination with regard to successive germ cell stages (spermatozoa, spermatids, spermatocytes, and spermatogonia), every second week two other untreated virgin females were placed with each male for mating. The uteri of the females were inspected on the 15th day of gestation, and preimplantation loss and postimplantation loss determined from dominant lethal parameters. Exposure of mice germ cells to ATI did not impair mating activity of males. Pregnancy rates were reduced (∼5–10%) by treatment of males with higher doses of ATI, but differences between treatment and control groups were not statistically significant ( P > 0.05). In the females bred to ATI-treated males, significant increase in preimplantation loss was observed at post-injection week 1 (reflecting exposure to spermatozoa) and 3 (reflecting exposure to mid and early spermatids) for higher doses of the inhibitor ( P < 0.05 or P < 0.01). During mating days 15–21 a statistically significant increase in postimplantation loss and dominant lethal effects were observed for all doses of ATI. At higher doses, dominant lethal effects were restricted to spermatozoa ( P < 0.01). These data suggest that ATI induces dominant lethal mutations at postmeiotic stages of spermatogenesis, but spermatids are the most sensitive cell stage to the effect of ATI. These preliminary findings show that ATI may be one of the factors causing disturbances in spermatogenesis leading to a reduction of host reproductive success.

Prenatal developmental toxicity studies of inhaled methyl iodide vapor in rabbits reveal a susceptible window of exposure inducing late gestational fetotoxicity

Methyl iodide (MeI), an intermediate used in the manufacture of some insecticides and pharmaceuticals, is under review for U.S. registration as a non-ozone-depleting alternative to methyl bromide in the pre-plant soil fumigation market. Guideline (OPPTS 870.3700) developmental toxicity studies in New Zealand White (NZW) rabbits showed dose-dependent increases in the litter proportions of late fetal deaths and postimplantation loss and/or decreased fetal body weight following inhalation exposure of pregnant rabbits to MeI during gestation days (GD) 6–28. A subsequent phased-exposure study was performed to pinpoint the critical window of gestational exposure that produced the rabbit fetotoxicity. Artificially inseminated NZW female rabbits were exposed to 20 ppm MeI vapors by whole-body inhalation (6 h/day) throughout major organogenesis and fetal development (GD 6–28), during early gestation (GD 6–14) or mid-gestation (GD 15–22) only, or during 2-day intervals late in gestation (GD 23–24, 25–26, or 27–28). No maternal or developmental toxicity was elicited from maternal exposure during GD 6–14, 15–22, or 27–28. However, MeI-related fetotoxicity, including increased litter proportions of late fetal deaths with or without corresponding decreases in fetal body weight, were observed for females exposed during GD 6–28 (p < .01), 23–24 and 25–26. Although the increase in late-stage fetal death for each of the 2-day exposures on GD 23–24 and GD 25–26 was not statistically significant, as noted for the combined total of fetal deaths during the GD 6–28 exposure, it can be deduced that the gestational window of GD 23–26 was the most susceptible window of exposure for eliciting developmental toxicity in rabbits exposed to MeI vapors.

Chronic exposure to fine particulate matter emitted by traffic affects reproductive and fetal outcomes in mice

Air pollution is an important environmental health risk factor that can result in many different gestational and reproductive negative outcomes. In this study, we have investigated the effects of two different times of exposure (before conception and during pregnancy) to urban ambient particulate matter on reproductive and pregnancy outcomes in mice. Using exposure chambers receiving filtered (F) and non-filtered (NF) air, we observed that exposed females exhibited changes in the length of estrus cycle and extended estrus and, therefore, a reduction in the number of cycles during the studied period (F 2.6±0.22 and NF 1.2±0.29, p=0.03). The mean number of antral follicles declined by 36% ( p=0.04) in NF mice (75±35.2) compared to F mice (118.6±18.4). Our results further indicate a significant increase in time necessary for mating and decreased fertility and pregnancy indices ( p=0.003) in NF couples. Mean post-implantation loss rates were increased by 70% ( p⩽0.005) in the NF2 group (exposed before and during pregnancy to NF air) compared to the F1 group (exposed before and during pregnancy to F air) and were influenced by both pre-gestational ( p<0.004) and gestational ( p<0.01) period exposure. Fetal weight was significantly higher in the F1 group when compared with the other groups ( p<0.001), at a 20% higher weight in the F1 group (0.86±0.18 g) than in the NF2 group (0.68±0.10 g). Furthermore, fetal weight was influenced by both pre-gestational and gestational period exposure, and a significant interaction between these two factors was found ( p<0.001). This study demonstrated that exposure to ambient levels of urban traffic-generated particulate matter negatively affects different functions and stages of the reproductive process. Our results also reinforce the idea that maternal exposure to air pollution is linked to negative pregnancy outcomes, even if the exposure occurs only before conception.

Abortifacient potentials of the aqueous extract of Bambusa vulgaris leaves in pregnant Dutch rabbits

Background There is the claim in the folklore medicine of Nigeria of the use of Bambusa vulgaris leaves as an abortifacient. However, there has not been any scientific evidence in the literature that substantiated or refuted this claim. Study Design Pregnant Dutch rabbits weighing 1.62–1.70 kg were randomized into three groups. Group A (control) was orally administered with 1.85 mL/kg body weight of distilled water (vehicle), thrice daily on Days 18–20 of pregnancy, while Groups B and C were treated like the control group except they received 250 and 500 mg/kg body weight of the aqueous extract of B. vulgaris leaves. Results Preliminary chemical screening of the aqueous extract of B. vulgaris leaves revealed the presence of alkaloids, tannins, phenolics, glycosides, saponins, flavonoids and anthraquinones. Clinical toxicity symptoms such as respiratory distress, salivation, weight loss, dull eyes, diarrhea, change in the appearance of fur as well as mortality were not observed in the animals at any period of the experiment. The 250 mg/kg body weight of the extract decreased (p<.05) the number of live fetus, whereas the 500 mg/kg body weight produced no live fetus. The 250 and 500 mg/kg body weight of the extract reduced the survival rate of the fetus to 29% and 0%, whereas the same doses produced abortion at the rate of 60% and 100%, respectively. The implantation index and preimplantation loss compared well with the control. Both doses increased the resorption index and postimplantation loss. The extract also decreased the concentrations of serum progesterone, follicle-stimulating and luteinizing hormones. While there was no effect on the weight of the uterus, uterine/body weight ratio, length of the right uterine horn and uterine cholesterol, the alkaline phosphatase activity and glucose concentration decreased significantly. The extract also provoked vaginal opening. Conclusion This study has substantiated the abortifacient potential of the aqueous extract of B. vulgaris leaves. The mechanism of abortion could possibly be through changes in the implantation site, altered hormone levels and, partly, estrogenicity. All these may be attributed, at least, in part to the phytoconstituents.

Maternal toxicity of nonsteroidal anti-inflammatory drugs as an important factor affecting prenatal development

Purpose Treatment-related signs of maternal toxicity, intrauterine growth retardation, increased skeletal developmental variations, and decreased bone ossification have been reported previously in rats exposed to high doses of non-selective cyclooxygenase (COX) inhibitors (ibuprofen, piroxicam, and tolmetin), also known as nonsteroidal anti-inflammatory drugs (NSAID). On the other hand, decrease in fetal length has been the only sign of toxicity found after exposure to selective COX-2 inhibitor (DFU). The aim of the study was to evaluate maternal effects on selected developmental abnormalities. Methods Data on postimplantation loss, fetal weight and length, placental weight, external and skeletal malformations and developmental variations were examined in the control and common COX-inhibitors-exposed groups, in relation to selected maternal blood biochemical parameters. Results Abnormal maternal urea level was found in mothers that gave birth to litters with low fetal weights and high incidence of skeletal malformations. Increased incidence of developmental variations and higher placental weights were also noted in this group. The number of litters with postimplantation loss, external malformations, external and skeletal variations was higher for dams with abnormal urea levels. A high incidence of external developmental variations was also seen in the offspring of dams with abnormal protein level. The highest embryo and/or fetal mortality were revealed in litters of dams with high urea and low total protein levels, simultaneously. In utero exposure to the examined COX-inhibitors increased the risk of developmental skeletal variations (OR = 1.74). Conclusion Maternal toxicity is an important factor affecting prenatal development during in utero exposure to nonsteroidal anti-inflammatory drugs.

Chronic dietary exposure to a low-dose mixture of genistein and vinclozolin modifies the reproductive axis, testis transcriptome, and fertility.

BackgroundThe reproductive consequences and mechanisms of action of chronic exposure to low-dose endocrine disruptors are poorly understood.ObjectiveWe assessed the effects of a continuous, low-dose exposure to a phytoestrogen (genistein) and/or an antiandrogenic food contaminant (vinclozolin) on the male reproductive tract and fertility.MethodsMale rats were exposed by gavage to genistein and vinclozolin from conception to adulthood, alone or in combination, at low doses (1 mg/kg/day) or higher doses (10 and 30 mg/kg/day). We studied a number of standard reproductive toxicology end points and also assessed testicular mRNA expression profiles using long-oligonucleotide microarrays.ResultsThe low-dose mixture and high-dose vinclozolin produced the most significant alterations in adults: decreased sperm counts, reduced sperm motion parameters, decreased litter sizes, and increased post implantation loss. Testicular mRNA expression profiles for these exposure conditions were strongly correlated. Functional clustering indicated that many of the genes induced belong to the “neuroactive ligand-receptor interactions” family encompassing several hormonally related actors (e.g., follicle-stimulating hormone and its receptor). All exposure conditions decreased the levels of mRNAs involved in ribosome function, indicating probable decreased protein production.ConclusionsOur study shows that chronic exposure to a mixture of a dose of a phytoestrogen equivalent to that in the human diet and a low dose—albeit not environmental—of a common anti-androgenic food contaminant may seriously affect the male reproductive tract and fertility.

Effects of gestational exposure to chlorpyrifos on implantation and neonatal mice

Exposure to some organophosphate (OP) compounds during pregnancy has been associated with adverse health consequence on both the mother and the offspring. The aim of the study was to evaluate the effect of exposure to chlorpyrifos (CPF) during gestation on implantation and on some neonatal parameters in mice. Twenty one virgin Swiss albino mice divided into 3 groups of 7 mice each served as subjects for this study. Mice in group 1 were dosed with corn oil (control), while those in groups 2 and 3 were exposed to CPF at a dose of 15.9 mg/kg (~15% LD50) and 21.2 mg/kg (~20% LD50), respectively. All the dams were dosed between gestation days (GD) 6 - 15 and monitored for signs of toxicity and gestation length. At birth, the litter size and weight, and the anogenital distance of the pups were measured. The pups were evaluated for physical characteristics and death. The dams were sacrificed at postnatal day 22, and the uterine horns evaluated for number of implantation sites. The results showed a significant decrease in the litter size and weight, and anogenital distance in pups exposed to CPF in utero compared to the control. In addition, all the pups prenatally exposed to CPF were born weak and died few days postpartum. A dose-dependent increase in percentage postimplantation loss was observed in mice dosed with CPF. In conclusion, exposure of pregnant mice to CPF caused increased gestation length, and postimplantation loss, decreased litter size and weight, survivability and anogenital distance.

Toxicological reproductive study of Cassia occidentalis L. in female Wistar rats

Ethnopharmacological relevance Cassia occidentalis L. (Leguminosae) has long been used as natural medicine in rainforests and other tropical regions for the treatment of inflammation, fever, liver disorders, constipation, worms, fungal infections, ulcers, respiratory infections, snakebite and as a potent abortifacient. Aim of the study This study has investigated the effects of oral sub-acute administration of Cassia occidentalis during pregnancy in female Wistar rats. Materials and methods Three groups of pregnant rats were treated orally from the 1st to the 6th day (pre-implantation period) and from the 7th to the 14th day (organogenic period) of pregnancy, with doses of 250 and 500 mg/kg. On the 20th day of pregnancy, the animals were euthanized and reproductive parameters evaluated. Results The results revealed no statistically significant differences between the control and treated groups in terms of offspring/dam relationship; fetuses, placentae and ovaries weights; number of implantation and resorption sites; number of corpora lutea in the ovaries and pre- and post-implantation loss rates. However, the presence of dead fetuses was registered in both doses of 250 and 500 mg/kg of Cassia occidentalis. Conclusions Further studies should therefore be conducted to obtain more detailed characteristics of the toxic effects of this species, the use of which is not recommended during pregnancy.