Birth defects research. Part B, Developmental and reproductive toxicology最新文献

{"title":"Exposure Duration-Dependent Ovarian Recovery in Methoxychlor-Treated Mice","authors":"Lawrence V. Tannenbaum,&nbsp;Jodi A. Flaws","doi":"10.1002/bdrb.21164","DOIUrl":"https://doi.org/10.1002/bdrb.21164","url":null,"abstract":"<p>The pesticide methoxychlor (MXC) is known to target ovarian antral follicles in the mouse. In previous in vivo studies, MXC administration for 20 days increased atresia, but did not affect female fertility immediately after dosing. Thus, we hypothesized that perhaps not enough time had elapsed between the onset of MXC-induced atresia and actual follicle loss to result in reduced fertility. The current study was undertaken to determine whether MXC treatment for 20 days results in reduced antral follicle numbers and fertility at 30 and 60 days after dosing. To test this hypothesis, adult CD-1 female mice were dosed with vehicle control or MXC (64 mg/kg/day) for 20 days. At 30 and 60 days postdosing, the mice were either subjected to fertility tests or their ovaries were collected and subjected to histological evaluation of follicle numbers and atresia. The results indicate that at 30 days after the completion of dosing, MXC significantly increased atresia and reduced primordial and total follicle numbers, but did not affect fertility compared to controls. At 60 days after completion of dosing, MXC did not significantly affect fertility, follicle numbers, or atresia compared to controls. Collectively, these data indicate that the ovary may be able to recover from MXC treatment for 20 days</p>","PeriodicalId":9120,"journal":{"name":"Birth defects research. Part B, Developmental and reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrb.21164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91820712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure Duration-Dependent Ovarian Recovery in Methoxychlor-Treated Mice.","authors":"L. Tannenbaum, J. Flaws","doi":"10.1002/bdrb.21164","DOIUrl":"https://doi.org/10.1002/bdrb.21164","url":null,"abstract":"The pesticide methoxychlor (MXC) is known to target ovarian antral follicles in the mouse. In previous in vivo studies, MXC administration for 20 days increased atresia, but did not affect female fertility immediately after dosing. Thus, we hypothesized that perhaps not enough time had elapsed between the onset of MXC-induced atresia and actual follicle loss to result in reduced fertility. The current study was undertaken to determine whether MXC treatment for 20 days results in reduced antral follicle numbers and fertility at 30 and 60 days after dosing. To test this hypothesis, adult CD-1 female mice were dosed with vehicle control or MXC (64 mg/kg/day) for 20 days. At 30 and 60 days postdosing, the mice were either subjected to fertility tests or their ovaries were collected and subjected to histological evaluation of follicle numbers and atresia. The results indicate that at 30 days after the completion of dosing, MXC significantly increased atresia and reduced primordial and total follicle numbers, but did not affect fertility compared to controls. At 60 days after completion of dosing, MXC did not significantly affect fertility, follicle numbers, or atresia compared to controls. Collectively, these data indicate that the ovary may be able to recover from MXC treatment for 20 days.","PeriodicalId":9120,"journal":{"name":"Birth defects research. Part B, Developmental and reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79747167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Age, Duration of Exposure, and Dose of Atrazine on Sexual Maturation and the Luteinizing Hormone Surge in the Female Sprague–Dawley Rat","authors":"Charles B. Breckenridge,&nbsp;Pragati Sawhney Coder,&nbsp;Merrill O. Tisdel,&nbsp;James W. Simpkins,&nbsp;Kun Don Yi,&nbsp;Chad D. Foradori,&nbsp;Robert J. Handa","doi":"10.1002/bdrb.21154","DOIUrl":"10.1002/bdrb.21154","url":null,"abstract":"<div>\u0000 <p>Atrazine (ATZ) was administered daily by gavage to pregnant female Sprague Dawley rats at doses of 0, 6.25, 25 or 50 mg/kg/day, either during gestation, lactation and post-weaning (G/L/PW cohort) to F₁ generation female offspring or only from postnatal day (PND 21) until five days after sexual maturation (vaginal opening) when the estrogen-primed, luteinizing hormone (LH) surge was evaluated (PW cohort). Additional subgroups of F₁ females received the vehicle or ATZ from PND 21–133 or from PND 120–133. Slight reductions in fertility and the percentage of F₁ generation pups surviving to PND 21 in the gestationally exposed 50 mg/kg dose group were accompanied by decreased food intake and body weight of dams and F₁ generation offspring. The onset of puberty was delayed in of the F₁ generation G/L/PW females at doses of 25 and 50 mg/kg/day. F₁ generation females in the PW high-dose ATZ group also experienced a delay in the onset of puberty. ATZ had no effect on peak LH or LH AUC in ovariectomized rats 5 days after sexual maturation, irrespective of whether the F₁ generation females were treated from gestation onward or only peripubertally. There was no effect of ATZ treatment on the estrous cycle, peak LH or LH AUC of F₁ generation females exposed from gestation through to PND 133 or only for two weeks from PND 120–133. These results indicate that developing females exposed to ATZ are not more sensitive compared to animals exposed to ATZ as young adults</p>\u0000 </div>","PeriodicalId":9120,"journal":{"name":"Birth defects research. Part B, Developmental and reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrb.21154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34232907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Maternal Exposure to Piperonyl Butoxide (PBO) on Behavioral Development in F1-Generation Mice","authors":"Toyohito Tanaka,&nbsp;Akiko Inomata","doi":"10.1002/bdrb.21163","DOIUrl":"10.1002/bdrb.21163","url":null,"abstract":"<p>Female mice were exposed maternally to piperonyl butoxide (PBO) through diet to provide dietary levels of 0% (control), 0.01%, 0.03%, and 0.09% during gestation and lactation periods, and selected reproductive and neurobehavioral parameters were measured in the F₁ generation. There was no adverse effect of PBO on litter size, litter weight, or sex ratio at birth. The average body weights of male offspring decreased significantly in dose-related manners on postnatal days (PNDs) 0, 4, 7, and 14 (<i>p</i> = 0.0019, 0.0096, 0.033, and 0.038, respectively) during the lactation period. In female offspring, the average body weights decreased in dose-related manners on PNDs 0, 4, 7, and 14 (<i>p</i> = 0.0027, 0.0104, 0.0193, and 0.0062, respectively). The survival of dams slightly decreased (<i>p</i> = 0.0209) in the high-dose group during the lactation period. With respect to behavioral developmental parameters, surface righting on PND 7 of male and female offspring was delayed significantly in a dose-related manner (<i>p</i> &lt; 0.001 in each). Swimming direction on PND 7 of male offspring was delayed significantly in a dose-related manner (<i>p</i> &lt; 0.01), and for female offspring it was delayed significantly in the high-dose group (<i>p</i> &lt; 0.05). Swimming head angle on PND 7 of male offspring was delayed significantly in a dose-related manner (<i>p</i> &lt; 0.05). Spontaneous behavior examination in males indicated that rearing increased in the high-dose group in the F₁ generation. The dose levels of PBO in the present study produced some adverse effects in neurobehavioral parameters in mice</p>","PeriodicalId":9120,"journal":{"name":"Birth defects research. Part B, Developmental and reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrb.21163","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34226014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Dofetilide on the Heart Rate of GD11 and GD13 Rat Embryos, in vivo, Using Ultrasound","authors":"Helen Ritchie,&nbsp;Diana Oakes,&nbsp;Tzong-tyng Hung,&nbsp;Elizabeth Hegedus,&nbsp;Shreya Sood,&nbsp;William Webster","doi":"10.1002/bdrb.21162","DOIUrl":"10.1002/bdrb.21162","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>There are a wide range of drugs including antidepressants, anticonvulsants and antipsychotics that cause embryonic bradycardia in vitro but it is unknown if they have a similar effect in vivo. One way to verify whether these in vitro findings are replicated in vivo is by the use of ultrasound examination of dosed pregnant rats. We tested this by examining the effect of dofetilide on embryonic heart rate (HR) in vivo using ultrasound.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Rats were dosed with dofetilide (4 or 2.5 mg/kg) on GD11 or (5 or 2.5 mg/kg) on GD13 and embryonic HR assessed by ultrasound, 2 and 24 hr later. Fetuses were examined for malformations on GD20.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>HR of control rat embryos showed a wide range at each gestational day. Dosing with dofetilide on GD11 caused severe bradycardia (∼60% reduction) 2 hours after dosing with recovery after 24 h of &gt;60% of LD but death and slow HR among the HD embryos. At term, 32% of the LD surviving fetuses had hypoplastic upper lip while &gt;90% of HD embryos had died. On GD13, embryonic HR was reduced in a dose-dependent manner with &gt;85% of LD and HD recovered by 24 hr. At term, all LD fetuses were normal while 29% of HD fetuses had limb defects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CONCLUSIONS</h3>\u0000 \u0000 <p>Ultrasound is a useful technique to investigate the effect of maternally administered drugs on the embryonic HR in the rat. The results may provide more information about the safety of these drugs in pregnancy leading to better risk assessment for the human</p>\u0000 </section>\u0000 </div>","PeriodicalId":9120,"journal":{"name":"Birth defects research. Part B, Developmental and reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrb.21162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34032432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Early Postnatal NSAID Treatment on Nephrogenesis in Wistar Rats","authors":"Ruud R. G. Bueters,&nbsp;Annelies Klaasen,&nbsp;Nuria Maicas,&nbsp;Sandrine Florquin,&nbsp;Lambertus P. van den Heuvel,&nbsp;Michiel F. Schreuder","doi":"10.1002/bdrb.21161","DOIUrl":"10.1002/bdrb.21161","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>Prematurely born children with patent ductus arteriosus are treated with ibuprofen or indomethacin, which may inhibit kidney development. We determined whether clinical doses affected kidney development and function, with or without extrauterine growth retardation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Wistar rats were cross-fostered in normal food (NF) or food restricted (FR) litters at postnatal day (PND) 2. On PND 3 to 4, three doses of 0.9% NaCl, 0.1 mg/kg indomethacin, or 10 mg/kg ibuprofen were administered via intraperitoneal injection with 12-hr intervals. Kidneys were evaluated for apoptosis, proliferation, and gene expression at PND 8; stereological assessment of nephron number at PND 35; and clinical pathology and neutrophil gelatinase-associated lipocalin at 4 and 9 months. Blood pressure was measured at the ages of 4, 6, and 9 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>NF and FR bodyweight differed from PND 3 onwards, ranging from 16.5 g at weaning (<i>p</i> &lt; 0.001) to 39 g at necropsy (<i>p</i> = 0.019). Kidney proliferation/apoptosis ratios were 7:1 and 3:1 (<i>p</i> = 0.001), respectively and different expression of <i>Wnt4</i> (0.7x<i>), Oat1</i> (1.3x), <i>Nphs1</i> (1.7x), <i>and Aqp4</i> (1.3x) was noted (but its biological relevance doubted). Nephron numbers were decreased by 12% (<i>p</i> = 0.109) in the ibuprofen-NF group and 7.5% (<i>p</i> = 0.237) in FR groups. This coincided with a tendency to increased neutrophil gelatinase-associated lipocalin at 9 months. No differences were noted in electrolytes, creatinine, or urea clearance. No valid blood pressure results could be obtained.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CONCLUSION</h3>\u0000 \u0000 <p>A clinical Ibuprofen dose showed potential to inhibit kidney development in neonatal rats. FR did not modulate these effects</p>\u0000 </section>\u0000 </div>","PeriodicalId":9120,"journal":{"name":"Birth defects research. Part B, Developmental and reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrb.21161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34076150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Himatanthus sucuuba in Maternal Reproductive Outcome and Fetal Anomaly Frequency in Rats","authors":"Thaigra de Sousa Soares,&nbsp;Débora Cristina Damasceno,&nbsp;Wilma De Grava Kempinas,&nbsp;Flávia Mayara Campos Resende,&nbsp;Maria Aparecida Correa dos Santos,&nbsp;Clélia Akiko Hiruma-Lima,&nbsp;Gustavo Tadeu Volpato","doi":"10.1002/bdrb.21152","DOIUrl":"10.1002/bdrb.21152","url":null,"abstract":"<p>The aim of this study was to evaluate the effect of <i>Himatanthus sucuuba</i> on the maternal reproductive outcome and fetal anomaly incidence in rats. Pregnant rats were randomly divided into three experimental groups as follows: Control = treated with water (vehicle), treated 250 = treated with <i>H. sucuuba</i> at dose 250 mg/kg, and treated 500 = treated with <i>H. sucuuba</i> at dose 500 mg/kg. The rats were orally treated, by <i>gavage</i>, with <i>H. sucuuba</i> or vehicle (water) during preimplantation and organogenic period (from gestational day 0–14). At day 21 of pregnancy, all rats were killed to obtain maternal–fetal data. The treatment with <i>H. sucuuba</i> at dose of 250 mg/kg caused reduction in placental efficiency and an increase preimplantation loss rate and placenta weight compared with the control. The treated 500 group presented a significant decrease in maternal weight gain, maternal weight gain minus gravid uterus weight, fetal weight, and placental efficiency compared with the control. In this group, there was a decrease in body weight at day 20 of pregnancy and metacarpus ossification and an increase in the preimplantation loss rate and skeletal anomalies compared with other groups. <i>Himatanthus sucuuba</i> extract caused intrauterine growth restriction, preimplantation loss, and developmental delay in the high doses tested</p>","PeriodicalId":9120,"journal":{"name":"Birth defects research. Part B, Developmental and reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrb.21152","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33977974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Exposure to Atrazine on Dopaminergic Development in Pubertal Male SD Rats","authors":"Yan-Shu Li,&nbsp;Xi He,&nbsp;Kun Ma,&nbsp;Yan-Ping Wu,&nbsp;Bai-Xiang Li","doi":"10.1002/bdrb.21151","DOIUrl":"10.1002/bdrb.21151","url":null,"abstract":"<p>Atrazine (ATR, 2-chloro-4-ethylamino-6-isopropylamino-s-triazine) is used worldwide as a herbicide, and its presence in the environment has resulted in documented human exposure. A lack of strong evidence for genetic heritability of idiopathic Parkinson's disease has focused attention on environmental toxicants in the disease etiology, particularly agrichemicals. Parkinson's disease is associated with advanced age and is characterized by the degeneration of dopaminergic neurons, but it is unclear whether specific neuronal damage could result from insults during development. The juvenile period is particularly vulnerable to environmental agent, therefore, we evaluated the effects of a 28-day exposure to ATR on the dopaminergic system in pubertal rats. Sprague–Dawley rats were treated orally with ATR at 50, 100, and 200 mg/kg bw, daily from postnatal days 27 to 54. In this study, we examined the hypothesis that pubertal exposure to ATR would disrupt the development of the nigrostriatal dopamine (DA) system. The content of DA and levodopa (L-DA) were examined in striatum samples by HPLC-FL, and the mRNA and protein expression of tyrosine hydroxylase, orphan nuclear hormone receptor (Nurr1), Nurr1 interacting protein (NuIP), and cyclin-dependent kinase inhibitors of the Cip̲Kip family (p57kip2) were examined in samples of the nigrostriatum by use of fluorescence Real-Time quantitative polymerase chain reaction (PCR). Exposure of juvenile rats to the high dose of ATR led to reduced levels of DA and L-DA, genes expression of NuIP, Nurr1, and p57kip2 in animals</p>","PeriodicalId":9120,"journal":{"name":"Birth defects research. Part B, Developmental and reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrb.21151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33971085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Valproic Acid Induces the Hyperacetylation of P53, Expression of P53 Target Genes, and Markers of the Intrinsic Apoptotic Pathway in Midorganogenesis Murine Limbs","authors":"France-Hélène Paradis,&nbsp;Barbara F. Hales","doi":"10.1002/bdrb.21149","DOIUrl":"10.1002/bdrb.21149","url":null,"abstract":"<p>In utero exposure to valproic acid (VPA), an anticonvulsant and histone deacetylase inhibitor (HDACi), increases the risk of congenital malformations. Although the mechanisms leading to the teratogenicity of VPA remain unsolved, several HDAC inhibitors increase cell death in cancer cell lines and embryonic tissues. Moreover, P53, the master regulator of apoptosis, is an established HDAC target. The purpose of this study was to investigate the effects of VPA on P53 signaling and markers of apoptosis during midorganogenesis in vitro limb development. Timed-pregnant CD1 mice (gestation day 12) were euthanized; embryonic forelimbs were excised and cultured in vitro for 3, 6, 12, or 24 hr in the presence or absence of VPA or valpromide (VPD), a non-HDACi analog of VPA. Quantitative RT-PCR and Western blots were used to assess the expression of candidate genes and proteins involved in P53 signaling and apoptosis. P53 hyperacetylation and a decrease (<i>Survivin/Birc5</i> and <i>Bcl2</i>) or an increase (<i>p21</i>/<i>Cdkn1a)</i> in the expression of p53 target genes was observed only in VPA-exposed limbs. VPA exposure also triggered an increase in markers of apoptosis and DNA damage; the concentrations of cleaved caspase 9 and caspase 3, cleaved-poly (ADP-ribose) polymerase, and γ-H2AX were increased in VPA-exposed limbs. VPD treatment caused a small but significant increase in cleaved caspase 3. Thus, in vitro exposure to an HDACi such as VPA leads to P53 hyperacetylation, enhances the expression of P53 target genes, and triggers an increase in apoptosis that may contribute to teratogenicity</p>","PeriodicalId":9120,"journal":{"name":"Birth defects research. Part B, Developmental and reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrb.21149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33947354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reproductive and Developmental Toxicity of Orally Administered Botanical Composition, UP446-Part I: Effects on Embryo-Fetal Development in New Zealand White Rabbits and Sprague Dawley Rats","authors":"Mesfin Yimam,&nbsp;Young-Chul Lee,&nbsp;Eu-Jin Hyun,&nbsp;Qi Jia","doi":"10.1002/bdrb.21150","DOIUrl":"10.1002/bdrb.21150","url":null,"abstract":"<p>The pharmacotoxicology impacts of dietary supplements taken at the time of pregnancy have remained alarming since women are the frequent herbal medicine users in many countries as a complement to the conventional pregnancy management. The use of herbal medicines and diet supplements in expectant mothers linked closely to the health of the childbearing mothers and the fetuses where the lack of developmental safety data imposes a challenge to make the right choices. Here, we describe the potential adverse effects of UP446, a standardized bioflavonoid composition from the roots of <i>Scutellaria baicalensis</i> and the heartwoods of <i>Acacia catechu</i>, on embryo-fetal development following maternal exposure during the critical period of major organogenesis in rabbits and rats. Pregnant dams were treated orally with UP446 at doses of 250, 500, and 1000 mg/kg/day during gestation. The number of resorptions, implantations, litter size, body weights, and skeletal development was evaluated. Maternal food intake and body, tissue, and placenta weight were also assessed. There were no statistically significant differences in implantation, congenital malformation, embryo-fetal mortalities, and fetuses sex ratios in all dosing groups of both species. Therefore, the no observed adverse effect level of UP446 was considered to be greater than 1000 mg/kg in both the maternal and fetus in both species</p>","PeriodicalId":9120,"journal":{"name":"Birth defects research. Part B, Developmental and reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrb.21150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33948039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}