Integrated geophysical investigation of recent earth tremors in Nigeria using aeromagnetic and gravity data.

Understanding the tectonics at active sites of recent seismic activities in Nigeria is fundamental towards disaster mitigation and emergency planning. We apply geophysical techniques of gravity and magnetic methods to investigate crustal depths, subsurface geologic faults and fractures, and the overall subsurface interaction at Mpape region and environs. Estimated depths to the bottom of magnetic crust (basal depths) range between 11.0 and 11.4 km at the Mpape region and decrease further southward towards Guabe town. This signifies the depth range of the active crust within the region. Comparative deeper basal depths (15.0-16.2 km) were obtained at locations farther from Mpape-Guabe towns at Nasarawa, Rubochi, and Fuka regions, showing a more stable region away from Mpape region. Computed Moho depths from gravity data show deeper depths at the Mpape region (~ 34.1 km) suggesting that the active crust exists in the upper crust. Two-dimensional modeling analysis along a profile taken across the Mpape region shows a conspicuous subsurface basement intrusion at the Mpape region with deep faults and fractures reaching depths of 7-14 km. Shallow basal depths at the Mpape region resulting from significant subsurface intrusion and concentrated subsurface faults at the intruded region may be responsible for the instability of the Mpape region. The most affected area is located within the Mpape-Guabe towns. We recommend the establishment of seismic monitoring facilities in this area for effective monitoring and evaluation.

Epigenetic Remodeling through Downregulation of Polycomb Repressive Complex 2 Mediates Chemotherapy Resistance in Testicular Germ Cell Tumors.

A greater understanding of the hypersensitivity and curability of testicular germ cell tumors (TGCTs) has the potential to inform strategies to sensitize other solid tumors to conventional chemotherapies. The mechanisms of cisplatin hypersensitivity and resistance in embryonal carcinoma (EC), the stem cells of TGCTs, remain largely undefined. To study the mechanisms of cisplatin resistance we generated a large panel of independently derived, acquired resistant clones from three distinct parental EC models employing a protocol designed to match standard of care regimens of TGCT patients. Transcriptomics revealed highly significant expression changes shared between resistant cells regardless of their parental origin. This was dominated by a highly significant enrichment of genes normally repressed by H3K27 methylation and the polycomb repressive complex 2 (PRC2) which correlated with a substantial decrease in global H3K27me3, H2AK119 ubiquitination, and expression of BMI1. Importantly, repression of H3K27 methylation with the EZH2 inhibitor GSK-126 conferred cisplatin resistance to parental cells while induction of H3K27 methylation with the histone lysine demethylase inhibitor GSK-J4 resulted in increased cisplatin sensitivity to resistant cells. A gene signature based on H3K27me gene enrichment was associated with an increased rate of recurrent/progressive disease in testicular cancer patients. Our data indicates that repression of H3K27 methylation is a mechanism of cisplatin acquired resistance in TGCTs and that restoration of PRC2 complex function is a viable approach to overcome treatment failure.

Plantas medicinais da Bacia do Rio das Velhas: avaliação das condições para produção e uso em saúde pública / Medicinal plants of the Rio das Velhas watershed region: potential for production and use in public health

RESUMO O desenvolvimento de projetos que contemplem o cultivo e beneficiamento de plantas medicinais, com qualidade, é urgente e necessário, especialmente quando se considera a expansão da oferta desses produtos para o Sistema Único de Saúde (SUS). Nesta pesquisa, foi avaliada a existência de iniciativas que produzem e disponibilizam plantas medicinais de interesse do SUS, em municípios que compõem a Bacia Hidrográfica do Rio das Velhas (BHRV), em Minas Gerais. Foram visitados 45 municípios da Bacia buscando informações sobre atividades já existentes de produção e uso coletivo de plantas medicinais. Os dados sobre plantas medicinais já existentes foram posteriormente confrontados com informações epidemiológicas, como as principais causas de internações hospitalares e cobertura de equipes da Estratégia da Saúde da Família (ESF). A pesquisa evidenciou a existência de atividades filantrópicas e comerciais, relativas à utilização coletiva de plantas medicinais, apenas em Belo Horizonte, Capim Branco, Curvelo, Lassance, Nova Lima e Sete Lagoas. Vinte e sete espécies, nativas e exóticas, presentes na RDC 10/2010 da Anvisa são produzidas nessas iniciativas, e elas ocorrem tanto de forma espontânea como por meio de cultivo. A correlação das principais causas de internação hospitalar com as espécies vegetais disponíveis revelou potenciais locais de aproveitamento das plantas, inclusive pela ESF. O desenvolvimento da cadeia produtiva, trabalhando desde o cultivo até a dispensação aos usuários do SUS, pode representar uma oportunidade de integração de diferentes atores e instituições da região, além de incrementar o desenvolvimento econômico-social e a preservação da biodiversidade local.

ABSTRACT The development of projects that include the cultivation and processing of medicinal plants with quality is urgent and necessary, especially when considering the offer increase of these products to the Unified Health System (SUS). In this study, we evaluated the potential of the Rio das Velhas" watershed region (BHRV) in producing and using medicinal plants. We visited 45 cities of the watershed, seeking information about existing production and collective use of medicinal plants. Afterwards, the data obtained in the fieldwork were confronted with epidemiological information, such as hospitalization rates and coverage of the Family Health Strategy. The research showed the existence of commercial and philanthropic activities in Belo Horizonte, Capim Branco, Curvelo, Lassance, Nova Lima and Sete Lagoas. Twenty-seven species, native and exotic ones, included in the 10/2010 Resolution edited by the Brazilian Health Surveillance Agency (Anvisa), are produced in these initiatives, and they occur both spontaneously and through cultivation. The correlation of the leading causes for hospitalization and the available plant species showed potential use of local plants, including by the Family Health Strategy. The development of the production chain, from the plants" cultivation to the medicines" dispensation for the SUS users, may represent an opportunity of integration of different actors and institutions in the region, besides increasing the economic and social development and contributing to the preservation of local biodiversity.

Klf9 is necessary and sufficient for Purkinje cell survival in organotypic culture.

During their phase of developmental programmed cell death (PCD), neurons depend on target-released trophic factors for survival. After this period, however, they critically change as their survival becomes target-independent. The molecular mechanisms underlying this major transition remain poorly understood. Here, we investigated, which transcription factors (TFs) might be responsible for the closure of PCD. We used Purkinje cells as a model since their PCD is restricted to the first postnatal week in the mouse cerebellum. Transcriptome analysis of Purkinje cells during or after PCD allowed the identification of Krüppel like factor 9 (Klf9) as a candidate for PCD closure, given its high increase of expression at the end of the 1st postnatal week. Klf9 function was tested in organotypic cultures, through lentiviral vector-mediated manipulation of Klf9 expression. In absence of trophic factors, the Purkinje cell survival rate is of 40%. Overexpression of Klf9 during PCD dramatically increases the Purkinje cell survival rate from 40% to 88%, whereas its down-regulation decreases it to 14%. Accordingly, in organotypic cultures of Klf9 knockout animals, Purkinje cell survival rate is reduced by half as compared to wild-type mice. Furthermore, the absence of Klf9 could be rescued by Purkinje cell trophic factors, Insulin growth factor-1 and Neurotrophin3. Altogether, our results ascribe a clear role of Klf9 in Purkinje cell survival. Thus, we propose that Klf9 might be a key molecule involved in turning off the phase of Purkinje PCD.

Hepatitis C Virus infection in apparentenly healthy individuals with family history of diabetes in Vom, Plateau State Nigeria.

Hepatitis C virus (HCV) infection is an important public health problem worldwide. Its association with, and predisposing nature for diabetes mellitus (DM) has been long established. This research was carried out to determine the prevalence of Hepatitis C virus (HCV) amongst people with possible genetic predisposition to diabetes mellitus living in and around Vom, Plateau State, Nigeria. 188 subjects were screened after they filled a structured questionnaire to determine some of their demographic data, social habits and possible risk factors. 5 ml of blood was collected from each subject and sera separated out. Biotech's third generation ELISA Kit for HCV antibodies was used for the screening. Liver enzyme analysis was carried out on positive samples to determine their disease status. A prevalence of 14.36% was recorded with the highest seropositive group being those in the age bracket of 18 - 37 years. 13(13.40%) of males and 14(15.38%) of females were sero-positive. Liver enzyme analysis of sero-positive subjects showed increased levels which may imply early onset of liver damage. These result showed that these individuals could later suffer diabetes which may be triggered by their HCV infection if not treated. This is not over-looking the economic significance of their ill health, assuming they progress to cirrhotic HCV or develop hepatocelluar carcinoma due to HCV chronicity.

Pediatric susceptibility to 18 industrial chemicals: a comparative analysis of newborn with young animals.

We comprehensively re-analyzed the toxicity data for 18 industrial chemicals from repeated oral exposures in newborn and young rats, which were previously published. Two new toxicity endpoints specific to this comparative analysis were identified, the first, the presumed no observed adverse effect level (pNOAEL) was estimated based on results of both main and dose-finding studies, and the second, the presumed unequivocally toxic level (pUETL) was defined as a clear toxic dose giving similar severity in both newborn and young rats. Based on the analyses of both pNOAEL and pUETL ratios between the different ages, newborn rats demonstrated greater susceptibility (at most 8-fold) to nearly two thirds of these 18 chemicals (mostly phenolic substances), and less or nearly equal sensitivity to the other chemicals. Exceptionally one chemical only showed toxicity in newborn rats. In addition, Benchmark Dose Lower Bound (BMDL) estimates were calculated as an alternative endpoint. Most BMDLs were comparable to their corresponding pNOAELs and the overall correlation coefficient was 0.904. We discussed how our results can be incorporated into chemical risk assessment approaches to protect pediatric health from direct oral exposure to chemicals.

Evaluation of developmental toxicity of 1-butanol given to rats in drinking water throughout pregnancy.

The objective of this study was to evaluate the developmental toxicity of 1-butanol in rats. Pregnant rats were given drinking water containing 1-butanol at 0.2%, 1.0% or 5.0% (316, 1454 or 5654 mg/kg/day) on days 0-20 of pregnancy. A significant decrease in maternal body weight gain accompanied by reduced food and water consumption was found at 5.0%. No significant increase in the incidence of pre- and postimplantation embryonic loss was observed in any groups treated with 1-butanol. Fetal weight was significantly lowered at 5.0%. Although a significant increase in the incidence of fetuses with skeletal variations and decreased degree of ossification was found at 5.0%, no increase in the incidence of fetuses with external, skeletal and internal abnormalities was detected in any groups treated with 1-butanol. The data demonstrate that 1-butanol is developmental toxic only at maternal toxic doses. No evidence for teratogenicity of 1-butanol was noted in rats. Based on the significant decreases in maternal body weight gain and fetal weight, it is concluded that the no observed adverse effect levels (NOAELs) of 1-butanol for both dams and fetuses are 1.0% (1454 mg/kg/day) in rats.

Evaluation of developmental toxicity of beta-thujaplicin (hinokitiol) following oral administration during organogenesis in rats.

The objective of this study was to evaluate the developmental toxicity of beta-thujaplicin (TP) in rats. Pregnant rats were given TP by gastric intubation at 15, 45, or 135 mg/kg on days 6-15 of pregnancy. The maternal body weight gain during administration at 45 and 135 mg/kg and after administration at 136 mg/kg and adjusted weight gain at 45 and 135 mg/kg were significantly reduced. A significant decrease in food consumption during and after administration was found at 45 and 135 mg/kg. A significant increase in the incidence of postimplantation loss was found in pregnant rats given TP at 135 mg/kg. A significantly lower weight was found in female fetuses at 45 and 135 mg/kg and in male fetuses at 135 mg/kg. Although a significantly increased incidence of fetuses with skeletal variations and decreased degree of ossification were found at 135 mg/kg, no significant increase in external, skeletal and internal malformations was detected after administration of TP. The data demonstrated that TP had adverse effects on embryonic/fetal survival and growth only at maternal toxic doses. No adverse effects on morphological development were found in rats fetuses. Based on the significant decreases in maternal body weight gain and weight of female fetuses at 45 mg/kg and higher, it is concluded that the no-observed-adverse-effect levels (NOAELs) of TP for both dams and fetuses are considered to be 15 mg/kg in rats.

Toxic effects of butyltin trichloride during early pregnancy in rats.

The objective of this study was to determine the toxic effects of butyltin trichloride (BTCl) during early pregnancy. Following successful mating, female rats were given BTCl by gastric intubation at 0,56,226, or 903 mg/kg on days 0-3 or 4-7 of pregnancy. Female rats were sacrificed on day 20 of pregnancy and fetuses were examined for number, abnormality, mortality, and weight. The maternal body weight gain and food consumption during the administration period was significantly decreased after administration of BTCl at 903 mg/kg on days 0-3 or 4-7 of pregnancy. The pregnancy rate in the BTCl-treated groups was comparable to the control value, regardless of the days on which BTCl was given. The incidence of pre-implantation embryonic loss was not significantly affected after administration of BTCl on days 0-3 or 4-7. In females having implantations, the numbers of corpora lutea, implantations, and live fetuses and the incidences of pre- and postimplantation loss in the groups given BTCl on days 0-3 were comparable to the controls. Although a significant increase in the incidence of postimplantation loss was observed after administration of BTCl on days 4-7 at 56 mg/kg, this change was small and inconsistent across doses and seems unlikely to be toxicologically significant. A significant decrease in weight of female fetuses was found after administration of BTCl at 903 mg/kg on days 0-3 or 4-7. It could be concluded that BTCl treatment during early pregnancy is maternal and developmental toxic at 903 mg/kg.

Effects of monobutyl phthalate on reproductive function in pregnant and pseudopregnant rats.

The effects of monobutyl phthalate (MBuP) on reproductive function were determined in pregnant and pseudopregnant rats. Rats were given MBuP by gastric intubation at 250, 500, 750, or 1000 mg/kg on days 0 to 8 of pregnancy and pregnancy outcome was determined on day 20 of pregnancy. The effects of MBuP on the uterine function, as a cause of early embryonic loss, were also determined in pseudopregnant rats, with an induced decidual cell response. The same doses of MBuP were given to pseudopregnant rats on days 0 to 8 of pseudopregnancy and the uterine weight on day 9 served as an index of uterine decidualization. MBuP at 1000 mg/kg caused significant increases in the incidences of preimplantation loss in females successfully mated and of postimplantation loss in females having implantations. Uterine decidualization in pseudopregnant rats was significantly decreased at 1000 mg/kg. These findings suggest that early embryonic loss due to MBuP is mediated, at least in part, via suppression of uterine decidualization, an impairment of uterine function.

Defective development of secretory neurones in the hypothalamus of Arnt2-knockout mice.

BACKGROUND: Within the basic region-helix-loop-helix (bHLH)-PAS family of transcription factors, Arnt and Arnt2 play unique roles; these two factors not only heterodimerize with themselves, but also with other members of this family and they act as transcription regulators which bind to specific DNA elements. Whereas Arnt is broadly expressed in various tissues, the expression of Arnt2 is known to be limited to the neural tissues. RESULTS: To elucidate the function of Arnt2 in detail, we cloned the mouse Arnt2 gene and its gene structure was determined. We subsequently generated germ line Arnt2 mutant mice by gene targeting technology. Heterozygous Arnt2 mice were viable, but homozygous Arnt2 gene knockout mice died shortly after birth. Histological and immunological analyses revealed that the supraoptic nuclei (SON) and the paraventricular nuclei (PVN) are hypocellular. Moreover, secretory neurones identified by the expression of neurosecretory hormone such as arginine vasopressin, oxytocin, corticotrophin-releasing hormone and somatostatin are completely absent in SON and PVN in the mutant Arnt2 mice. Consistent with these observations, prospective SON and PVN neurones which express Brn2 appeared around E13.5 in the mantle zone, but no neurones which expressed the neurosecretory hormones were found in the SON and PVN regions. CONCLUSIONS: These data show that the transcription factor Arnt2 controls the development of the secretory neurones at the later or final stages of differentiation rather than at the beginning stage. Strikingly similar observations have been reported with the Sim1 deficient mice. Taken together, our results demonstrate that Arnt2 is an indispensable transcription factor for the development of the hypothalamus, and suggest that Arnt2 is an obligatory partner molecule of Sim1 in the developmental process of the neuroendocrinological cell lineages.

Adverse effects on development of the reproductive system in male offspring of rats given monobutyl phthalate, a metabolite of dibutyl phthalate, during late pregnancy.

The objective of this study was to determine the adverse effects of monobutyl phthalate (MBuP), a major metabolite of dibutyl phthalate (DBP), on development of the reproductive system in offspring following maternal administration during late pregnancy, and to assess the role of MBuP in the antiandrogenic effects of DBP. Pregnant rats were given MBuP by gastric intubation at 250, 500, or 750 mg/kg on days 15 through 17 of pregnancy. Maternal body weight gain and food consumption during the administration period were significantly decreased at 500 mg/kg and higher and at 750 mg/kg, respectively. A significant increase in the incidence of postimplantation embryonic loss was found at 500 mg/kg and higher. The body weights of male and female fetuses were significantly lower at 750 mg/kg. A significant increase in the incidence of fetuses with undescended testes was found at 250 mg/kg and higher. A significant decrease in the anogenital distance (AGD) of male fetuses was observed at 250 mg/kg and higher. The AGD/body weight ratio and AGD/cube root of body weight ratio in male fetuses was also significantly reduced at 250 mg/kg and higher. The AGD, AGD/body weight ratio and AGD/cube root of body weight ratio in female fetuses in the MBuP-treated groups were comparable to those in the control group. The present study indicates that MBuP on days 15 to 17 of pregnancy produced adverse effects on the development of reproductive system in male offspring and suggest that MBuP may be responsible for the induction of the antiandrogenic effects of DBP.

Effects of 4-tert-octylphenol on initiation and maintenance of pregnancy following oral administration during early pregnancy in rats.

4-tert-Octylphenol (OP) is an alkylphenol that is an intermediate in the production of alkylphenol ethoxylates. OP has been reported to be the most potent estrogenic alkylphenol in vitro. In the present study, the effects of OP on initiation and maintenance of pregnancy were investigated in rats. Inseminated female rats were orally given OP at 0,15.6,31.3,62.5 and 125 mg/kg on day 0 through day 8 of pregnancy. Female rats were sacrificed on day 20 of pregnancy, and pregnancy outcome was determined. Decreases in body weight gain and food consumption on days 0-9 were found at 31.3 mg/kg and above, and at 15.6 mg/kg and above, respectively. The pregnancy rate was not adversely affected by OP administration during early pregnancy even at 125 mg/kg. The incidence of post-implantation loss per litter at 31.3 mg/kg and above was significantly higher than that in the control group. The body weights of live fetuses in the OP-treated groups were not significantly different from those in the control group. No increase in the incidence of fetuses with external malformations was found in any OP-treated group. We concluded that OP during early pregnancy caused post-implantation embryonic loss at doses that showed maternal toxicity.

Rat two-generation reproductive toxicity study of bisphenol A.

This study was conducted to determine the low-dose effects of bisphenol A (BPA) in a rat two-generation reproduction study. Groups of 25 male and 25 female Crj: CD (SD) IGS rats were given BPA at 0.2, 2, 20, or 200 microg/kg/day by gastric intubation throughout the study beginning at the onset of a 10- and 2-week premating period, in F0 males and females, respectively, and continuing through the mating, gestation, and lactation periods, for two generations. There were adult (F0, F1, F2) and postnatal day (PND) 22 (F1, F2) necropsies: the oldest F2 males and females being killed at postnatal weeks 7 and 14, respectively. No compound-related clinical signs or effects on body weight or food consumption were observed in any generation. There were no compound-related changes in surface righting reflex, negative geotaxis reflex, mid-air righting reflex, pinna detachment, incisor eruption, eye opening, testes descent, preputial separation, or vaginal opening in F1 and F2 generations, or behavior in the open field or water filled multiple T-maze in the F1 generation. No test compound-related changes in estrous cyclicity, copulation index, fertility index, number of implantations, gestation length, litter size, pup weight, pup sex ratio, pup viability, or other functional reproductive measures were noted in any generation. A few significant changes in the anogenital distance (AGD) per cube root of body weight ratio were found at 0.2 and 20 microg/kg in F1 males, at 2, 20, and 200 microg/kg in F1 females, and at 20 and 200 microg/kg in F2 females. However, the changes in the AGD were consistently small (within 5% of control values), and no continuous changes in the AGD or AGD/cube root of body weight ratio were detected. There were no compound-related changes in epididymal sperm counts or motility in F0 and F1 males. No compound-related necropsy findings or effects on organ weight including the reproductive organs were found in any generation. Histopathologic examinations revealed no evidence of compound-related changes in any organs including the reproductive organs of both sexes. The data indicate that oral doses of BPA of between 0.2 and 200 microg/kg over 2 generations did not cause significant compound-related changes in reproductive or developmental parameters in rats.

Adverse effects of dibutyltin dichloride on initiation and maintenance of rat pregnancy.

The present study was conducted to evaluate the adverse effects of dibutyltin dichloride (DBTCl) on initiation and maintenance of pregnancy after maternal exposure during early pregnancy in rats. After successful mating, female rats were given DBTCl by gastric intubation on Days 0 to 3 or on Days 4 to 7 of pregnancy at 0, 3.8, 7.6, or 15.2 mg/kg. Food-restricted pregnant rats were given an amount of feed equal to the feed intake of female rats treated with DBTCl at 15.2 mg/kg on Days 0 to 3 or on Days 4 to 7 of pregnancy. Female rats were sacrificed on Day 20 of pregnancy and pregnancy outcome was determined. After administration of DBTCl on Days 0 to 3, the rate of nonpregnant females and the incidence of preimplantation embryonic loss in the 7.6 mg/kg group were significantly higher than those in the control group, and those in the 15.2 mg/kg group were significantly higher than those in the control and pair-fed groups. In females with implantations, the numbers of implantations and live fetuses and the incidence of postimplantation embryonic loss in the groups given DBTCl on Days 0 to 3 were not significantly different from those in the control group. The incidence of postimplantation embryonic loss in the groups given DBTCl on Days 4 to 7 at 7.6 and 15.2 mg/kg was significantly higher than that in the control and pair-fed groups. It can be concluded that DBTCl adversely affects initiation and maintenance of pregnancy when administered during early pregnancy and that the manifestations of the adverse effects of DBTCl vary with the gestational stage at the time of maternal exposure.

Effects of dibutyl phthalate on reproductive function in pregnant and pseudopregnant rats.

In our previous studies, dibutyl phthalate (DBP) was found to be embryolethal and teratogenic in rats. In this study, the effects of DBP on reproductive function were investigated on pregnant and pseudopregnant rats. Rats were given DBP by gastric intubation at 0, 250, 500, 750, 1000, 1250 or 1500 mg/kg on Days 0 to 8 of pregnancy and the pregnancy outcome was determined on Day 20 of pregnancy. The same doses of DBP were given to pseudopregnant rats, with an induced decidual cell response, on Days 0 to 8 of pseudopregnancy, and the uterine weight on Day 9 served as an index of the uterine decidualization. DBP caused significant increases in the incidences of preimplantation loss in females successfully mated at 1250 and 1500 mg/kg and of postimplantation loss in females having implantations at 750 mg/kg and above. The uterine decidualization in pseudopregnant rats was significantly decreased at 750 mg/kg and above. These findings suggest that early embryonic loss due to DBP may be mediated, at least in part, via the suppression of uterine decidualization, an impairment of uterine function.

Critical period for adverse effects on development of reproductive system in male offspring of rats given di-n-butyl phthalate during late pregnancy.

The objective of this study was to determine the susceptible days for the adverse effects of di-n-butyl phthalate (DBP) on development of reproductive system in male offspring following maternal administration on successive 3-day period during late pregnancy. Pregnant rats were given DBP by gastric intubation at 1000 or 1500 mg/kg on days 12-14 or 18-20 of pregnancy or at 500, 1000 or 1500 mg/kg on days 15-17 of pregnancy. A significant decrease in the maternal body weight gain and/or food consumption was found in the DBP-treated groups regardless of the days on which DBP at 1000 and 1500 mg/kg was given. A significant increase in the number of resorptions per litter was found in the groups given DBP at 1500 mg/kg on days 12-14 and 15-17 of pregnancy. The weights of male and female fetuses were significantly decreased in the groups given DBP at 1000 and 1500 mg/kg on days 12-14 and 18-20 and at 1500 mg/kg on days 15-17. A significant increase in the incidence of fetuses with undescended testes was found at 1500 mg/kg on days 12-14 and at all doses on days 15-17. A significant decrease in the anogenital distance (AGD) of male fetuses was observed in the groups treated with DBP regardless of the days of treatment. The AGD/body weight ratio in male fetuses was significantly reduced in the groups given DBP on days 15-17, but neither on days 12-14 nor 18-20. The AGD of female fetuses in the DBP-treated groups was comparable to that in the control group. It was concluded that period of days 15-17 of pregnancy was the most susceptible for DBP-induced undescended testes and decreased AGD in male offspring.

Suppression of decidual cell response induced by tributyltin chloride in pseudopregnant rats: a cause of early embryonic loss.

In our previous studies, tributyltin chloride (TBTCl) at doses of 16.3 mg/kg and above caused implantation failure (preimplantation embryonic loss) and postimplantation embryonic loss in rats following administration on gestational day (GD) 0 through GD 3 and GD 4 through GD 7, respectively. This study was designed to assess the effects of TBTCl on uterine function as a cause of early embryonic loss in pseudopregnant rats. TBTCl was given orally to pseudopregnant rats at doses of 4.1, 8.1, 16.3 and 32.5 mg/kg on pseudopregnant day (PPD) 0 to PPD 3 or 8.1, 16.3, 32.5 and 65.1 mg/kg on PPD 4 to PPD 7. The decidual cell response was induced by bilateral scratch trauma on PPD 4. The uterine weight on PPD 9 served as an index of uterine decidualization. Uterine weight and serum progesterone levels on PPD 9 were significantly decreased after administration of TBTCl at doses of 16.3 mg/kg and above on PPD 0 to PPD 3 or PPD 4 to PPD 7. Administration of TBTCl at doses of 8.1 mg/kg and above on PPD 0 to 3 also significantly decreased serum progesterone levels on PPD 4. TBTCl had no effect on ovarian weight and number of corpora lutea. It can be concluded that TBTCl suppresses the uterine decidual cell response and decreases progesterone levels, and these effects are responsible for early embryonic loss due to TBTCl exposure.