RESUMO
The development of DBA/2J mouse strain embryos is nearly 12 h - or 6 somite pairs - delayed as compared to the outbred NMRI mouse embryos of the same age on gestation days (GD) 8-12. To evaluate inter-strain differences in susceptibility to teratogens, dams were treated with methylnitrosourea (MNU, 5 mg/kg body weight i.p.) on defined gestation days (NMRI: GD 9, 91/2 or 10; DBA/2J: GD 10 or 101/2). Skeletal anomalies produced by MNU on both mouse strains varied with the GD of treatment. The pattern of anomalies produced by MNU on a given GD markedly differed between the two mouse strains, yet they were similar -with a few exceptions- when exposures at equivalent embryonic stages are compared. Findings from this study indicated that strain-dependent differences in the developmental stage of mouse embryos of the same gestational age occur, a possibility that has been often neglected when inter-strain differences in susceptibility to developmental toxicants are interpreted.
Assuntos
Embrião de Mamíferos/anormalidades , Desenvolvimento Embrionário/efeitos dos fármacos , Metilnitrosoureia/toxicidade , Esqueleto/anormalidades , Somitos/anormalidades , Teratogênicos/toxicidade , Animais , Embrião de Mamíferos/efeitos dos fármacos , Feminino , Camundongos , Camundongos Endogâmicos DBA , Gravidez , Esqueleto/efeitos dos fármacos , Esqueleto/embriologia , Somitos/efeitos dos fármacos , Somitos/embriologiaRESUMO
ABSTRACT The development of DBA/2J mouse strain embryos is nearly 12 h - or 6 somite pairs - delayed as compared to the outbred NMRI mouse embryos of the same age on gestation days (GD) 8-12. To evaluate inter-strain differences in susceptibility to teratogens, dams were treated with methylnitrosourea (MNU, 5 mg/kg body weight i.p.) on defined gestation days (NMRI: GD 9, 91/2 or 10; DBA/2J: GD 10 or 101/2). Skeletal anomalies produced by MNU on both mouse strains varied with the GD of treatment. The pattern of anomalies produced by MNU on a given GD markedly differed between the two mouse strains, yet they were similar -with a few exceptions- when exposures at equivalent embryonic stages are compared. Findings from this study indicated that strain-dependent differences in the developmental stage of mouse embryos of the same gestational age occur, a possibility that has been often neglected when inter-strain differences in susceptibility to developmental toxicants are interpreted.
Assuntos
Animais , Feminino , Gravidez , Ratos , Esqueleto/anormalidades , Teratogênicos/toxicidade , Somitos/anormalidades , Desenvolvimento Embrionário/efeitos dos fármacos , Embrião de Mamíferos/anormalidades , Metilnitrosoureia/toxicidade , Esqueleto/efeitos dos fármacos , Esqueleto/embriologia , Somitos/efeitos dos fármacos , Somitos/embriologia , Embrião de Mamíferos/efeitos dos fármacos , Camundongos Endogâmicos DBARESUMO
Embryo-fetal development (EFD) studies, typically in pregnant rats and rabbits, are conducted prior to enrolling females of reproductive age in clinical trials. Common rabbit strains used are the New Zealand White (NZW) and Dutch Belted (DB). As fetal abnormalities can occur in all groups, including controls, Historical Control Data (HCD) is compiled using data from control groups of EFD studies, and is used along with each study's concurrent control group to help determine whether fetal abnormalities are caused by the test article or are part of background incidences. A probability analysis was conducted on 2014 HCD collected at Charles River Inc., Horsham PA on Covance NZW, Covance DB, and Charles River (CR) NZW rabbits. The analysis was designed to determine the probability of 2 or 3 out of a group of 22 does aborting their litter or of having a fetal abnormality by chance. Results demonstrate that pregnancy parameters and fetal observations differ not only between strains, but between sources of rabbits of the same strain. As a result the probability of these observations occurring by chance in two or three litters was drastically different. Although no one single strain is perfect, this analysis highlights the need to appreciate the inherent differences in pregnancy and fetal abnormalities between strains, and points out that an apparent isolated increased incidence of an observation in one strain will not necessarily be test-article related in another strain. A robust HCD is critical for interpretation of EFD rabbit studies, regardless of the rabbit strain used.
Assuntos
Desenvolvimento Embrionário , Desenvolvimento Fetal , Feto/embriologia , Coelhos/embriologia , Animais , Embrião de Mamíferos/anormalidades , Feminino , Feto/anormalidades , Gravidez , Probabilidade , ReproduçãoRESUMO
In this study, we investigated the reproductive capacity of pregnant rats exposed to daily orally administered powder-dehydrated reconstituted of Agaricus brasiliensis (=Agaricus blazei sensu Murrill), the fetal organogenesis, and the development of the pups. Pregnant rats were exposed for the entire gestational period to water (control) and A. brasiliensis at 300 or 600 mg/kg/day. Fertility and body weight of dams were monitored. Pups were monitored for body weight, offspring vitality, morphology, and physical and neurobehavioral development. An increase in sternebrae agenesis was observed at the 600 mg/kg/day dose of A. brasiliensis, while incomplete ossification of sternebrae was seen even at a 300 mg/kg/day dose. In conclusion, this study is the first to demonstrate the impact of maternal exposure to A. brasiliensis on the fetal organogenesis and development of offspring in a rat model. The 600 mg/kg/day dose showed some negative effects, and low toxicity was observed at the 300 mg/kg/day dose.
Assuntos
Basidiomycota , Embrião de Mamíferos/anormalidades , Animais , Feminino , Inocuidade dos Alimentos , Masculino , Gravidez , Ratos , Ratos Wistar , Esterno/anormalidadesRESUMO
STUDY DESIGN: To inhibit ß-catenin specifically signaling in chondrocytes Col2-ICAT transgenic mice were generated. Anomalies in caudal vertebrae were detected during embryonic and postnatal stages of Col2-ICAT transgenic mice. OBJECTIVE: To determine the role of canonical ß-catenin signaling in caudal vertebral development. SUMMARY OF BACKGROUND DATA: ß-catenin signaling plays a critical role in skeletal development. Col2-ICAT transgenic mice were generated to selectively block ß-catenin signaling by overexpression of the ICAT gene in chondrocytes. METHODS: Tails of E16.5 transgenic embryos and adult Col2-ICAT transgenic mice and their wild-type littermates were collected and analyzed. Skeletal preparation, 3-dimensional micro-computed tomographic and histological analyses were performed to evaluate changes in the structure of caudal vertebrae. Bromodeoxyuridine labeling was performed to evaluate changes in chondrocyte proliferation in caudal vertebrae. RESULTS: Skeletal preparation and 3-dimensional micro-computed tomographic analyses revealed bone deformation and angulated deformities in tail tissue in Col2-ICAT transgenic mice. Histological studies revealed abnormal bone development and dysplastic caudal vertebrae in Col2-ICAT transgenic mice. Inhibition of ß-catenin signaling in cartilage resulted in vertebral dysplasia leading to aberrant resegmenting process. Thus, 2 poorly developed sclerotomes failed to fuse to form a complete vertebrae. BrdU labeling revealed a decreased chondrocyte proliferation in both cartilageous templates of transgenic embryos and the growth plate of adult Col2-ICAT transgenic mice. CONCLUSION: Wnt/ß-catenin signaling plays an important role in vertebral development. Inhibition of ß-catenin signaling in chondrocytes results in caudal vertebra deformity in mice, which may occur as early as in the stage of sclerotome formation. LEVEL OF EVIDENCE: N/A.
Assuntos
Condrócitos/metabolismo , Transdução de Sinais , Coluna Vertebral/metabolismo , beta Catenina/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células , Condrócitos/citologia , Colágeno Tipo II/genética , Embrião de Mamíferos/anormalidades , Embrião de Mamíferos/metabolismo , Elementos Facilitadores Genéticos/genética , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Regiões Promotoras Genéticas/genética , Proteínas Repressoras , Coluna Vertebral/anormalidades , Coluna Vertebral/diagnóstico por imagem , Cauda/anormalidades , Cauda/diagnóstico por imagem , Cauda/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Microtomografia por Raio-X , beta Catenina/genéticaRESUMO
Assisted reproduction techniques have improved agricultural breeding in the bovine. However, important development steps may differ from the situation in vivo and there is a high mortality rate during the first trimester of gestation. To better understand these events, we investigated the development of embryos and fetal membranes following fixed-time AI (FTAI), IVF and nuclear transfer (NT). The onset of yolk-sac development was not normal in cloned embryos. Later steps differed from conditions in vivo in all three groups; the yolk-sac was yellowish and juxtaposed with the amniotic membrane. Vascularisation of the chorioallantoic membrane was relatively late and low in NT gestations, but normal in the others. The overall development of the embryos was normal, as indicated by morphology and regression analysis of growth rate. However, NT conceptuses were significantly smaller, with the livers in some embryos occupying the abdominal cavity and others exhibiting heart abnormalities. In conclusion, the yolk-sac and the cardiovascular system seem to be vulnerable to morphogenetic alterations. Future studies will focus on gene expression and early vascularisation processes to investigate whether these changes may be responsible for the high incidence of intrauterine mortality, especially in clones.
Assuntos
Bovinos/fisiologia , Embrião de Mamíferos/embriologia , Desenvolvimento Embrionário , Técnicas Reprodutivas/veterinária , Animais , Animais Endogâmicos , Brasil , Bovinos/genética , Clonagem de Organismos/métodos , Clonagem de Organismos/veterinária , Cruzamentos Genéticos , Perda do Embrião/etiologia , Perda do Embrião/veterinária , Embrião de Mamíferos/anormalidades , Membranas Extraembrionárias/anormalidades , Membranas Extraembrionárias/irrigação sanguínea , Feminino , Fertilização in vitro/efeitos adversos , Fertilização in vitro/veterinária , Morte Fetal/etiologia , Morte Fetal/veterinária , Cardiopatias Congênitas/etiologia , Cardiopatias Congênitas/veterinária , Inseminação Artificial/efeitos adversos , Inseminação Artificial/veterinária , Técnicas de Transferência Nuclear/efeitos adversos , Técnicas de Transferência Nuclear/veterinária , Placentação , Gravidez , Técnicas Reprodutivas/efeitos adversos , Saco Vitelino/anormalidadesRESUMO
BACKGROUND: Approximately 15% of misoprostol-induced-abortions may not be successful, leading to in utero exposure to the drug and to the induction of a series of defects including central nervous system, limb and visceral defects. A common proposal is that the drug causes disruption of the fetal vasculature leading to embryonic or fetal hypoxia. AIM: To evaluate the teratogenicity of misoprostol using the rat post-implantation embryo culture. MATERIAL AND METHODS: Rat embryos were collected at the beginning of organogenesis and cultured in rat serum containing misoprostol at concentrations of 200, 2,000 or 20,000 pg/ml. Functionality, morphology and morphometry parameters were evaluated. RESULTS: Misoprostol induced a dose-dependent embryotoxic effect causing a decrease in embryo viability and function (poor vascular development and survival) and morphometry (alterations in branchial arches, heart and cephalic portions of the neural tube, among others). CONCLUSIONS: All the manifestations observed are indicative of the ability of misoprostol to directly induce developmental retardation and alterations.
Assuntos
Anormalidades Induzidas por Medicamentos/embriologia , Abortivos não Esteroides/toxicidade , Embrião de Mamíferos/efeitos dos fármacos , Misoprostol/toxicidade , Animais , Embrião de Mamíferos/anormalidades , Feminino , Testes de Mutagenicidade/métodos , Gravidez , Ratos , Ratos Sprague-DawleyRESUMO
Background: Approximately 15 percent of misoprostol-induced-abortions may not be successful, leading to in utero exposure to the drug and to the induction of a series of defects including central nervous system, limb and visceral defects. A commonproposal is that the drug causes disruption of the fetal vasculature leading to embryonic or fetal hypoxia. Aim: To evaluate the teratogenicity of misoprostol using the rat post-implantation embryo culture. Material and Methods: Rat embryos were collected at the beginning of organogenesis and cultured in rat serum containing misoprostol at concentrations of 200, 2,000 or 20,000 pg/ml. Functionality, morphology and morphometry parameters were evaluated. Results: Misoprostol induced a dose-dependent embryotoxic effect causing a decrease in embryo viability and function (poor vascular development and survival) and morphometry (alterations in branchial arches, heart and cephalic portions of the neural tube, among others). Conclusions: All the manifestations observed are indicative of the ability of misoprostol to directly induce developmental retardation and alterations.
Assuntos
Animais , Feminino , Gravidez , Ratos , Anormalidades Induzidas por Medicamentos/embriologia , Abortivos não Esteroides/toxicidade , Embrião de Mamíferos/efeitos dos fármacos , Misoprostol/toxicidade , Embrião de Mamíferos/anormalidades , Testes de Mutagenicidade/métodos , Ratos Sprague-DawleyRESUMO
Background: Embryonic mortality is a major cause of reproductive failure in cattle, resulting in a lot of problems to the industry. Recently, many techniques have been used in the production of genetically modified animals mainly related to improve the animal production. The possibility to genetically manipulate living organisms through the addition or inactivation of genes has revolutionized the understanding of biological and molecular mechanisms. Herein, we showed data about what is known about the abnormalities in bovine conceptus using IVF and NT techniques. Review: The establishment of pregnancy results from the interaction between the trophoblast and maternal tissues. Embryonic/ fetal loss occurs throughout pregnancy in cattle; however, it is concentrated mainly in the first 42 days after breeding. Recently data have showed that approximately 50% of cloned bovine embryos do not establish the gestation after the transference of the blastocyst. In addition, placental abnormalities occur in high levels in cloned animals during the initial and in the end of gestation. Low viability of cloned embryos is mainly expressed by the reduction in the rate of deployment, the increased rate of perinatal mortality and fetal, and the various anomalies observed in newborn animals. Among the pregnancy complications from placental transfer of manipulated embryos (IVF and NT) there are changes in the morphology of the placentome, in the region of the fetal-maternal contact, increase of allantoic or amniotic fluid, vascularity, lower number of cotyledons, and increased of the interplacentomal area "Offspring Syndrome". In addition, the placenta, fetal membranes and umbilical cord from cloned animals have rudimentary development. According to Wells et al., the overall efficiency of cloning in bovine is limited to 5- 6%. In IVF pregnancies the placentome percentage, fetal villi, density and volume of binucleated cells is reduced. However, the volume of blood vessels in increased maternal wattles, believing there is a compensatory mechanism in the vascular network of the placentae. Conclusion: Many technological innovations could help to obtain a better quality production and significant improvements in animal breeding such as those brought about by nuclear transfer and in vitro fertilization. New studies on the dynamics of development in cattle embryology derived from nuclear transfer techniques and in vitro fertilization are necessary, focusing on different systems in order to find greater success in the artificial producing and selection of interest characteristics.
Assuntos
Animais , Bovinos , Placenta/anormalidades , Fertilização in vitro/métodos , Clonagem de Organismos/veterinária , Embrião de Mamíferos/anormalidades , Técnicas de Transferência Nuclear/veterináriaRESUMO
The congenital malformations in the off spring of diabetic mothers are the result of a multifactorial process. Susceptibility to the effects of maternal diabetes in the pathogenesis of these anomalies is influenced by the genetic background, indicating that there are polymorphic genes that modify the cellular response to hyperglycemia. The modifier genes for the teratogenic effect of maternal diabetes are yet unknown. An excessive glucose supply to embryonic tissues leads to a state of oxidative stress, which affects the expression of genes encoding scavenging enzymes such as super oxide dismutase (SOD) and catastases and activates development genes such as PAX3, involved in neural tube defects. Cell proliferation and cell death are important mechanisms underlying malformations in infants born to diabetic mothers. There is an increase of apoptotic Bax and caspase-3 proteins and a low expression of Bcl-Z ant apoptotic protein in embryos exposed to a diabetic environment. Hyperglycemia decreases intracellular levels of reduced GSH, prostaglandin EZ (PGEZ) and DNA synthesis in embryo's tissues. Understanding the molecular pathogenesis of diabetic embryopathy will allow the use of effective therapies for the prevention of teratogenic effects in diabetic mothers.
Assuntos
Animais , Feminino , Humanos , Gravidez , Ratos , Anormalidades Congênitas/embriologia , Hiperglicemia/complicações , Gravidez em Diabéticas , Apoptose/fisiologia , Anormalidades Congênitas/genética , Anormalidades Congênitas/fisiopatologia , Diabetes Mellitus Experimental/complicações , Embrião de Mamíferos/anormalidades , Hiperglicemia/fisiopatologia , Estresse Oxidativo/fisiologiaRESUMO
The congenital malformations in the off spring of diabetic mothers are the result of a multifactorial process. Susceptibility to the effects of maternal diabetes in the pathogenesis of these anomalies is influenced by the genetic background, indicating that there are polymorphic genes that modify the cellular response to hyperglycemia. The modifier genes for the teratogenic effect of maternal diabetes are yet unknown. An excessive glucose supply to embryonic tissues leads to a state of oxidative stress, which affects the expression of genes encoding scavenging enzymes such as super oxide dismutase (SOD) and catastases and activates development genes such as PAX3, involved in neural tube defects. Cell proliferation and cell death are important mechanisms underlying malformations in infants born to diabetic mothers. There is an increase of apoptotic Bax and caspase-3 proteins and a low expression of Bcl-Z ant apoptotic protein in embryos exposed to a diabetic environment. Hyperglycemia decreases intracellular levels of reduced GSH, prostaglandin EZ (PGEZ) and DNA synthesis in embryo's tissues. Understanding the molecular pathogenesis of diabetic embryopathy will allow the use of effective therapies for the prevention of teratogenic effects in diabetic mothers.
Assuntos
Anormalidades Congênitas/embriologia , Hiperglicemia/complicações , Gravidez em Diabéticas , Animais , Apoptose/fisiologia , Anormalidades Congênitas/genética , Anormalidades Congênitas/fisiopatologia , Diabetes Mellitus Experimental/complicações , Embrião de Mamíferos/anormalidades , Feminino , Humanos , Hiperglicemia/fisiopatologia , Estresse Oxidativo/fisiologia , Gravidez , RatosRESUMO
Cadmium (Cd) has an embryotoxic effect on laboratory animals expressed by growth retardation and induced craniofacial and skeletal malformations. Some of the mechanisms suggested to account for this reproduction damage include oxidative stress and lipoperoxidation. It has been shown that due to its antioxidant activity, glycine protects embryos from in vivo cadmium-induced teratogenicity. However, it is not known whether such protection may also be found in embryo cultures and what its possible mechanism of action might be. The purpose of this study was to determine whether the effect of glycine (1 mM) against the damage of CdCl(2) (1 microM) on the embryo, was direct or indirect. The amino acid was found to have significantly counteracted the effects of Cd by reducing the growth retardation and preventing the opening of the neural tube. Such protective effect seems to be partly due to decreased lipoperoxidation levels in embryos exposed to the metal, which would make it a direct effect.
Assuntos
Anormalidades Induzidas por Medicamentos/prevenção & controle , Cloreto de Cádmio/toxicidade , Glicinérgicos/farmacologia , Glicina/farmacologia , Teratogênicos/toxicidade , Animais , Antioxidantes/farmacologia , Embrião de Mamíferos/anormalidades , Embrião de Mamíferos/efeitos dos fármacos , Feminino , Retardo do Crescimento Fetal/induzido quimicamente , Retardo do Crescimento Fetal/prevenção & controle , Técnicas In Vitro , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/prevenção & controle , GravidezRESUMO
This study was designed to investigate the effect of vitrification and post-thaw survival and chromosomal aberrations caused by vitrification of vitrified 8-cell mouse embryos in comparison with a control group. To this purpose the survival rate and the frequency of chromosomal aberrations were assessed in frozen-thawed 8-cell mouse embryos after various storage durations in the presence of ethylene glycol as cryoprotectant. eight-cell mouse embryos were obtained from NMRI mice 3 days after mating. Retrieved embryos were transferred to vitrification solution containing ethylene glycol as cryoprotectant, then transferred into a vitrification straw using standard technique, and vitrified in liquid nitrogen. Six groups of embryos according to storage duration (24 hours, 1 and 2 weeks, 1-6 months) were frozen. After appropriate storage periods embryos were thawed and studied for their viability 4-6 hours after thawing and intact embryos were transferred to fresh medium containing colcemid. After 48 hours, the embryos were fixed and studied for their chromosome abnormalities using Tarkowsky's drying technique. Results indicate that freezing affects the viability and chromosome structure of embryos when compared with the control group. Furthermore increasing the storage duration reduces the viability and increases the chromosome aberrations of embryos (such as aneuploidy and polyploidy). This result might indicate that the effects of vitrification on the cytoskeleton or other cellular organelle might produce chromosomal alterations leading to cell death.
Assuntos
Aberrações Cromossômicas/embriologia , Criopreservação , Crioprotetores/farmacologia , Embrião de Mamíferos/anormalidades , Etilenoglicol/farmacologia , Congelamento , Animais , Camundongos , Fatores de TempoRESUMO
The effect of glycine in preventing cadmium (Cd) teratogenicity in mice was studied. Cadmium chloride (CdCl2) was administered subcutaneously at 1, 2 or 4 mg/kg doses on gestation days (GD) 7, 8 and 9. Glycine was given ad libitum (in the drinking water) from GD0 through GD18 (the day when animals were killed), as a 1% and 2% drinking water solution. Cd and nucleic acid concentrations in embryos were determined. The most common finding seen after CdCl2 4 mg/kg exposure was exencephaly. The incidence of this malformation was significantly reduced in mice receiving 2% glycine while fetal Cd significantly decreased as compared to cadmium-treated positive control animals. Increased nucleic acid levels were seen in the same embryos. In glycine non-supplemented mice given CdCl2 4 mg/kg, embryonic lipid peroxidation proved to be increased. In conclusion, lipid peroxidation was associated with cadmium-induced teratogenicity, and glycine inhibited the cadmium-induced effect by inhibiting placental transport of cadmium. However, further detailed studies are needed to establish the mechanism(s) of action.
Assuntos
Anormalidades Induzidas por Medicamentos/prevenção & controle , Cloreto de Cádmio/toxicidade , Embrião de Mamíferos/efeitos dos fármacos , Glicina/farmacologia , Teratogênicos/toxicidade , Anormalidades Induzidas por Medicamentos/patologia , Animais , DNA/análise , Relação Dose-Resposta a Droga , Antagonismo de Drogas , Embrião de Mamíferos/anormalidades , Embrião de Mamíferos/metabolismo , Feminino , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Camundongos , GravidezRESUMO
This study was desµgned to investµgate the effect of vitrification and post-thaw survival and chromosomal aberrations caused by vitrification of vitrified 8-cell mouse embryos in comparison with a controligroup. To this purpose the survival rate and the frequency of chromosomal aberrations were assessed in frozen-thawed 8-cell mouse embryos after various storage durations in the presence of ethyleneiglycol as cryoprotectant. eight-cell mouse embryos were obtained from NMRI mice 3 days after mating. Retrieved embryos were transferred to vitrification solution containing ethyleneiglycol as cryoprotectant, then transferred into a vitrification straw using standard technique, and vitrified in liquid nitrogen. Sixigroups of embryos according to storage duration (24 hours, 1 and 2 weeks, 1-6 months) were frozen. After appropriate storage periods embryos were thawed and studied for their viability 4-6 hours after thawing and intact embryos were transferred to fresh medium containing colcemid. After 48 hours, the embryos were fixed and studied for their chromosome abnormalities using Tarkowsky's drying technique. Results indicate that freezing affects the viability and chromosome structure of embryos when compared with the controligroup. Furthermore increasing the storage duration reduces the viability and increases the chromosome aberrations of embryos (such as aneuploidy and polyploidy). This result mµght indicate that the effects of vitrification on the cytoskeleton or other cellular organelle mµght produce chromosomal alterations leading to cell death.
Assuntos
Animais , Camundongos , Criopreservação , Aberrações Cromossômicas/embriologia , Crioprotetores/farmacologia , Embrião de Mamíferos/anormalidades , Etilenoglicol/farmacologia , Congelamento , Fatores de TempoRESUMO
The present study was performed to evaluate the long-term behavioral effect in offspring of a subteratogenic Cd dose administered by the oral route to Wistar rat during organogenesis. First, the teratogenic Cd dose was determined by treating pregnant rats with 20 mg/kg Cd from Day 6 to Day 14 of pregnancy and by visceral and skeletal analysis of their fetuses. In a second experiment, pregnant rats treated with this Cd dose were allowed to give birth and nurture their offspring. The physical and behavioral parameters of the offspring were analyzed in infancy and during adulthood. Results showed that Cd treatment during organogenesis (1) was not able to induce maternal toxicity; (2) induced external malformations; (3) increased significantly fetus anomalies and malformations, with reduced metacarpus ossification, cleft palate and right or left renal cavitation being observed in these animals; (4) did not modify pup body weight or weight gain during the lactation period; (5) improved testis descent and delayed the vaginal opening of pups; (6) did not modify ear unfolding, incisor eruption, eye opening, negative geotaxis or palmar grasp; (7) did not modify the open-field parameters and the stereotyped behavior of male or female pups; and (8) modified male sexual behavior and (9) reduced female sexual behavior. We conclude that prenatal exposure to a teratogenic Cd dose induced in the survivor animals several deleterious effects in their development as well as in adult behaviors, mainly in the sexual sphere.