Offspring Of Untreated Mothers Research Articles

Blocking Placental Class G Immunoglobulin Transfer Prevents NMDA Receptor Antibody Effects in Newborn Mice.

Background and ObjectivesTo determine in a mouse model whether neonatal Fc receptor (FcRn) blockade prevents the placental transfer of class G immunoglobulin (IgG) derived from patients with anti-NMDA receptor (NMDAR) encephalitis and their pathogenic effects on the fetuses and offspring.MethodsPregnant C57BL/6J mice were administered via tail vein FcRn antibody (FcRn-ab) or saline solution 6 hours before administration of patients' or controls' IgG on days 14, 15, and 16 of gestation. Three experimental groups were established: mice receiving controls' IgG, patients' IgG, or patients' IgG along with pretreatment with FcRn-ab. Immunohistochemical staining, confocal microscopy, hippocampal long-term potentiation, and standardized developmental and behavioral tasks were used to assess the efficacy of treatment with FcRn-ab.ResultsIn pregnant mice that received patients' IgG, treatment with FcRn-ab prevented the IgG from reaching the fetal brain, abrogating the decrease of NMDAR clusters and the reduction of cortical plate thickness that were observed in fetuses from untreated pregnant mice. Moreover, among the offspring of mothers that received patients' IgG, those whose mothers were treated with FcRn-ab did not develop the alterations that occurred in offspring of untreated mothers, including impairment in hippocampal plasticity, delay in innate reflexes, and visuospatial memory deficits.DiscussionFcRn blockade prevents placental transfer of IgG from patients with anti-NMDAR encephalitis and abrogates the synaptic and neurodevelopmental alterations caused by patients' antibodies. This model has potential therapeutic implications for other antibody-mediated diseases of the CNS during pregnancy.

Effects of maternal exposure to extract of Trichilia catigua on antibody production in the offspring of Wistar rats

It was evaluated the effects of maternal treatment with the Trichilia catigua (ExTc) crude extract on the antibodies’ production by their offspring. Female rats received ExTc or saline from the first day of pregnancy until the twenty-first day after the birth of the pups, when the pups were weaned. All pups were inoculated with two doses of 50 μg of IgY diluted in aluminium hydroxide/PBS on days 26 and 40 of life. Antibody levels were analysed by ELISA. Our results show an increase in levels of IgG1 and IgG2a anti-IgY in female offspring of mothers treated with ExTc compared to female offspring of untreated mothers. Furthermore, ExTc treatment suppressed the production of IgG2a anti-IgY antibodies in males. The data show that maternal exposure to ExTc can modulate the production of antibodies in the offspring.

Follow-up study of children whose mothers were treated with transcranial magnetic stimulation during pregnancy: preliminary results.

The purpose of this study is to determine the impact of repetitive transcranial stimulation (rTMS) treatment during pregnancy on neurodevelopment of children. Women who were treated with rTMS during pregnancy and delivered liveborn children between 2008 and 2013 were selected. A control group consisted of children whose mothers had a history of untreated depression during their pregnancy (N = 26). Early developmental characteristics of all the children in the study were evaluated, and their developmental levels were determined using the Ankara Developmental Screening Inventory. The mean age of the children in the rTMS treatment group was 32.4 months (range 16-64 months), and that of the untreated group was 29.04 (range 14-63 months). Jaundice (N = 2) and febrile convulsion (N = 1) were the reported medical conditions in the children of the rTMS-treated group; jaundice (N = 3) and low birth weight (N = 1) were reported in the untreated group. In the rTMS group, mothers' perception of delay in language development was observed, but there were not any statistically significant differences in the prevalence rate compared with the untreated group (OR = 0.38; 95% CI 0.0860-1.6580). Our results suggest that rTMS exposure during pregnancy is not associated with poorer cognitive or motor development outcomes in children aged 18-62 months. Although language development as reported by the mothers was found to be poorer than expected in the rTMS-treated group, the delay was found to be similar to the language delay observed in offspring of untreated mothers, as reported in previous studies of prenatal depression treated with selective serotonin reuptake inhibitors.

BPA and Insulin Resistance: Evidence of Effects in Dams and Offspring

Recent population studies have associated increased exposure to persistent organic pollutants with an elevated risk of insulin resistance and thus a greater likelihood of developing type 2 diabetes and heart disease. Among these chemicals is bisphenol A (BPA), a pervasive endocrine-disrupting compound used to make polycarbonate plastic and epoxy resins. Now researchers report evidence that exposure to environmentally relevant doses of BPA during pregnancy may alter insulin sensitivity and glucose homeostasis in mice, with potential disease-related consequences for both the mother and her male offspring [EHP 118(9):1243–1250; Alonso-Magdalena et al.]. The study evaluated the effects of two different doses of BPA (10 or 100 μg/kg/d) administered to pregnant mice during days 9–16 of gestation. Glucose metabolism experiments were performed on the mice during pregnancy and subsequently on their offspring. BPA exposure aggravated the insulin resistance that occurs during pregnancy, and four months postpartum, BPA-treated mice weighed more and had more severe insulin resistance than untreated females. The BPA-treated mice also showed elevated plasma levels of insulin, leptin, triglycerides, and glycerol (a breakdown product of triglycerides), as well as molecular changes indicating reduced insulin sensitivity in skeletal muscle and liver. Given that levels of the hormone leptin are normally increased during pregnancy, the authors propose that future research should seek to determine whether BPA directly regulates leptin release from fatty tissue or whether the observed hyperleptinemia is a consequence of the altered metabolic state of these animals. Previously the same research team had shown a relationship between BPA exposure and glucose intolerance and insulin resistance in adult male mice. In the present study, they further observed that, at 6 months of age, male offspring exposed to BPA in utero had reduced glucose tolerance, increased insulin resistance, and altered blood parameters compared with offspring of untreated mothers. Moreover, studies of the male offspring’s pancreases showed altered calcium signaling and insulin secretion. The authors conclude that BPA exposure during pregnancy can alter the mother’s glucose metabolism during pregnancy and later in life, and may contribute to metabolic disorders relevant to glucose homeostasis in the male offspring. The findings also suggest that BPA exposure should be further examined as a risk factor for diabetes.

Bisphenol A Exposure during Pregnancy Disrupts Glucose Homeostasis in Mothers and Adult Male Offspring

BackgroundBisphenol A (BPA) is a widespread endocrine-disrupting chemical used as the base compound in the manufacture of polycarbonate plastics. In humans, epidemiological evidence has associated BPA exposure in adults with higher risk of type 2 diabetes and heart disease.ObjectiveWe examined the action of environmentally relevant doses of BPA on glucose metabolism in mice during pregnancy and the impact of BPA exposure on these females later in life. We also investigated the consequences of in utero exposure to BPA on metabolic parameters and pancreatic function in offspring.MethodsPregnant mice were treated with either vehicle or BPA (10 or 100 μg/kg/day) during days 9–16 of gestation. Glucose metabolism experiments were performed on pregnant mice and their offspring.ResultsBPA exposure aggravated the insulin resistance produced during pregnancy and was associated with decreased glucose tolerance and increased plasma insulin, triglyceride, and leptin concentrations relative to controls. Insulin-stimulated Akt phosphorylation was reduced in skeletal muscle and liver of BPA-treated pregnant mice relative to controls. BPA exposure during gestation had long-term consequences for mothers: 4 months postpartum, treated females weighed more than untreated females and had higher plasma insulin, leptin, triglyceride, and glycerol levels and greater insulin resistance. At 6 months of age, male offspring exposed in utero had reduced glucose tolerance, increased insulin resistance, and altered blood parameters compared with offspring of untreated mothers. The islets of Langerhans from male offspring presented altered Ca2+ signaling and insulin secretion. BrdU (bromodeoxyuridine) incorporation into insulin-producing cells was reduced in the male progeny, yet β-cell mass was unchanged.ConclusionsOur findings suggest that BPA may contribute to metabolic disorders relevant to glucose homeostasis and that BPA may be a risk factor for diabetes.

Maternal panic disorder and congenital abnormalities: A population‐based case‐control study

Maternal panic disorder in pregnancy is the most common manifestation of anxiety disorders in Hungary. The association between panic disorder during pregnancy and structural birth defects, i.e., congenital abnormalities, was studied. The prevalence of maternal panic disorder in cases with different congenital abnormalities was compared to that of matched controls in the population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities. Of 22,843 cases with congenital abnormalities, 210 (0.9%) had mothers with panic disorder during pregnancy compared to 187 (0.5%) of 38,151 controls (adjusted prevalence odds ratio [POR] 1.6; 95% CI, 1.3-2.0). Specific groups of congenital abnormalities were also assessed versus controls. Cases with isolated cleft lip with or without cleft palate (CL/P) (adjusted POR, 3.4; 95% CI, 1.3-9.0) and multiple congenital abnormalities (adjusted POR, 3.0; 95% CI, 1.2-7.2) were more likely to have had mothers with panic disorder during the study pregnancy. Notably, among mothers with panic disorders, the associations were found only in offspring of untreated mothers. A higher rate of isolated CL/P and multiple congenital abnormalities may be caused by the direct biological effect of panic disorder or by the interaction of maternal panic disorder and lifestyle factors. Antipanic drug treatment seems to have a protective effect for isolated CL/P and multiple congenital abnormalities. Birth Defects Research (Part A), 2006.

Maternal phenylketonuria: Magnetic resonance imaging of the brain in offspring

Phenylketonuria (PKU) produces white matter changes identifiable by magnetic resonance imaging. These changes occur postnatally. Offspring of untreated mothers with PKU also have a brain effect, expressed as microcephaly and mental retardation. This effect occurs prenatally. To determine whether the white matter changes seen in PKU are also present in maternal PKU offspring, despite the different developmental stages of exposure to PKU, we performed brain magnetic resonance imaging studies in seven maternal PKU offspring, five from essentially untreated pregnancies and two from treated pregnancies. None had white matter changes, although the one offspring with PKU had delayed myelination. However, hypoplasia of the corpus callosum was present in three of the four offspring from untreated pregnancies and in the offspring from a maternal PKU pregnancy not treated until the third trimester. Unlike PKU, white matter changes are not a feature of the brain effect in maternal PKU. However, hypoplasia of the corpus callosum is a feature of maternal PKU and is probably a result of inhibition of corpus callosum development at 8 to 20 weeks of gestation. The hypoplastic corpus callosum could be a marker for brain effect in maternal PKU and may have implications for the cognitive deficits in these offspring. (J P EDIATR 1996;128:770-5)

Regulation of visual attention in offspring of female monkeys treated chronically with delta 9-tetrahydrocannabinol.

Visual attention was studied in a group of rhesus monkey infants whose mothers received daily oral treatment with low levels of delta 9-tetrahydrocannabinol (THC, 2,4 mg/kg/day) prior to and during pregnancy and throughout lactation (3.5 postnatal months). Attention was measured at 1 and 2 years of age in a standardized test situation in which animals looked at projected slides. In comparison with controls (offspring of untreated mothers), THC offspring directed more attention at slides on the 1st trial of a session. The THC offspring also engaged in relatively longer individual periods of attention on the 1st vs 2nd trials of the session and during the 1st vs 2nd session in which a given slide was presented. Further experiments varying novelty and complexity of visual stimuli suggested that changes in visual attention of THC offspring can be characterized as a failure to limit the response to novel stimuli.

Potentiation of Benzo[ ]pyrene Tumorigenesis in the Progeny of Female Hamsters Injected with Freund's Incomplete Adjuvant

SummarySarcomas induced by benzo[α] pyrene in the mature offspring of hamsters injected sc on the second day of pregnancy with Freund's incomplete adjuvant appeared earlier and grew more rapidly than did similarly induced tumors in the offspring of untreated mothers. Though females were intrinsically more susceptible than males to BP tumorigenesis, the enhancing effect of the adjuvant was approximately equal in male and female offspring.

Effect of perinatal administration of 7,12-dimethylbenz(a)anthracene on the later response to a subcutaneous teflon implant.

The possible effect of the exposure of mice during the perinatal period to minute doses of 7,12-dimethylbenz(a)anthracene (DMBA) on the response to a subcutaneous implantation later in life of a teflon disc was investigated. The present results indicate that the prenatal or neonatal exposure to DMBA had no effect on the incidence of tumors occurring around the teflon implant nor on the average age at death of mice bearing tumors at the site of the teflon implant. The incidence of tumors occurring at various sites was higher in the descendants of females given 400 μg DMBA during the late period of pregnancy than in offspring of untreated mothers which were given 0.1 μg DMBA at birth.