Early postnatal nutrition determines adult physical activity and energy expenditure in female mice

USDA-ARS?s Scientific Manuscript database

Decades of research in rodent models has shown that early postnatal overnutrition induces excess adiposity and other components of metabolic syndrome that persist into adulthood. The specific biologic mechanisms explaining the persistence of these effects, however, remain unknown. On postnatal day 1...

Embryonic mammary signature subsets are activated in Brca1-/- and basal-like breast cancers

PubMed Central

2013-01-01

Introduction Cancer is often suggested to result from development gone awry. Links between normal embryonic development and cancer biology have been postulated, but no defined genetic basis has been established. We recently published the first transcriptomic analysis of embryonic mammary cell populations. Embryonic mammary epithelial cells are an immature progenitor cell population, lacking differentiation markers, which is reflected in their very distinct genetic profiles when compared with those of their postnatal descendents. Methods We defined an embryonic mammary epithelial signature that incorporates the most highly expressed genes from embryonic mammary epithelium when compared with the postnatal mammary epithelial cells. We looked for activation of the embryonic mammary epithelial signature in mouse mammary tumors that formed in mice in which Brca1 had been conditionally deleted from the mammary epithelium and in human breast cancers to determine whether any genetic links exist between embryonic mammary cells and breast cancers. Results Small subsets of the embryonic mammary epithelial signature were consistently activated in mouse Brca1-/- tumors and human basal-like breast cancers, which encoded predominantly transcriptional regulators, cell-cycle, and actin cytoskeleton components. Other embryonic gene subsets were found activated in non-basal-like tumor subtypes and repressed in basal-like tumors, including regulators of neuronal differentiation, transcription, and cell biosynthesis. Several embryonic genes showed significant upregulation in estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and/or grade 3 breast cancers. Among them, the transcription factor, SOX11, a progenitor cell and lineage regulator of nonmammary cell types, is found highly expressed in some Brca1-/- mammary tumors. By using RNA interference to silence SOX11 expression in breast cancer cells, we found evidence that SOX11 regulates breast cancer cell

Early Postnatal Cardiomyocyte Proliferation Requires High Oxidative Energy Metabolism.

PubMed

de Carvalho, Ana Elisa Teófilo Saturi; Bassaneze, Vinícius; Forni, Maria Fernanda; Keusseyan, Aline Alfonso; Kowaltowski, Alicia Juliana; Krieger, José Eduardo

2017-11-13

Cardiac energy metabolism must cope with early postnatal changes in tissue oxygen tensions, hemodynamics, and cell proliferation to sustain development. Here, we tested the hypothesis that proliferating neonatal cardiomyocytes are dependent on high oxidative energy metabolism. We show that energy-related gene expression does not correlate with functional oxidative measurements in the developing heart. Gene expression analysis suggests a gradual overall upregulation of oxidative-related genes and pathways, whereas functional assessment in both cardiac tissue and cultured cardiomyocytes indicated that oxidative metabolism decreases between the first and seventh days after birth. Cardiomyocyte extracellular flux analysis indicated that the decrease in oxidative metabolism between the first and seventh days after birth was mostly related to lower rates of ATP-linked mitochondrial respiration, suggesting that overall energetic demands decrease during this period. In parallel, the proliferation rate was higher for early cardiomyocytes. Furthermore, in vitro nonlethal chemical inhibition of mitochondrial respiration reduced the proliferative capacity of early cardiomyocytes, indicating a high energy demand to sustain cardiomyocyte proliferation. Altogether, we provide evidence that early postnatal cardiomyocyte proliferative capacity correlates with high oxidative energy metabolism. The energy requirement decreases as the proliferation ceases in the following days, and both oxidative-dependent metabolism and anaerobic glycolysis subside.

Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm

PubMed Central

Aye, Christina Y L; Lewandowski, Adam J; Lamata, Pablo; Upton, Ross; Davis, Esther; Ohuma, Eric O; Kenworthy, Yvonne; Boardman, Henry; Wopperer, Samuel; Packham, Alice; Adwani, Satish; McCormick, Kenny; Papageorghiou, Aris T; Leeson, Paul

2017-01-01

Background Adults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development. Methods Cardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes. Results At birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P<0.001; right 39.3±38.1 vs. 16.6±40.8, P=0.002). Greater changes were associated with lower gestational age at birth (left P<0.001; right P=0.001). Conclusion Preterm offspring, including those born in late gestation, have a disproportionate increase in ventricular mass from birth up to 3 months of postnatal age. These differences were not present before birth. Early postnatal development may provide a window for interventions relevant to long-term cardiovascular health. PMID:28399117

Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm.

PubMed

Aye, Christina Y L; Lewandowski, Adam J; Lamata, Pablo; Upton, Ross; Davis, Esther; Ohuma, Eric O; Kenworthy, Yvonne; Boardman, Henry; Wopperer, Samuel; Packham, Alice; Adwani, Satish; McCormick, Kenny; Papageorghiou, Aris T; Leeson, Paul

2017-07-01

BackgroundAdults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development.MethodsCardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes.ResultsAt birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P<0.001; right 39.3±38.1 vs. 16.6±40.8, P=0.002). Greater changes were associated with lower gestational age at birth (left P<0.001; right P=0.001).ConclusionPreterm offspring, including those born in late gestation, have a disproportionate increase in ventricular mass from birth up to 3 months of postnatal age. These differences were not present before birth. Early postnatal development may provide a window for interventions relevant to long-term cardiovascular health.

Strain Differences in Dimethylbenz[a]anthracene-Induced Mammary Tumor Incidence in Long Evans and Sprague Dawley Rat Offspring Following Prenatal Atrazine Exposure

EPA Science Inventory

It has been shown that prenatal exposure to the chlorotriazine herbicide atrazine (ATR) during mammary bud outgrowth (late gestation) delays postnatal mammary epithelial progression in Long Evans (LE) rats. Our laboratory has recently found that prenatal exposure to ATR also effe...

Maternal postnatal psychiatric symptoms and infant temperament affect early mother-infant bonding.

PubMed

Nolvi, Saara; Karlsson, Linnea; Bridgett, David J; Pajulo, Marjukka; Tolvanen, Mimmi; Karlsson, Hasse

2016-05-01

Postnatal mother-infant bonding refers to the early emotional bond between mothers and infants. Although some factors, such as maternal mental health, especially postnatal depression, have been considered in relation to mother-infant bonding, few studies have investigated the role of infant temperament traits in early bonding. In this study, the effects of maternal postnatal depressive and anxiety symptoms and infant temperament traits on mother-infant bonding were examined using both mother and father reports of infant temperament. Data for this study came from the first phase of the FinnBrain Birth Cohort Study (n=102, father reports n=62). After controlling for maternal symptoms of depression and anxiety, mother-reported infant positive emotionality, measured by infant smiling was related to better mother-infant bonding. In contrast, infant negative emotionality, measured by infant distress to limitations was related to lower quality of bonding. In regards to father-report infant temperament, only infant distress to limitations (i.e., frustration/anger) was associated with lower quality of mother-infant bonding. These findings underline the importance of infant temperament as one factor contributing to early parent-infant relationships, and counseling parents in understanding and caring for infants with different temperament traits. Copyright © 2016 Elsevier Inc. All rights reserved.

[Electrophysiological characteristics of hippocampal postnatal early development mediated by AMPA receptors in rats].

PubMed

Chen, Xue-Yi; Zhang, Ai-Feng; Zhao, Wen; Gao, Yu-Dan; Duan, Hong-Mei; Hao, Peng; Yang, Zhao-Yang; Li, Xiao-Guang

2018-04-25

The present study was aimed to investigate the electrophysiological characteristics of hippocampal postnatal early development mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in rats. Forty-eight Wistar rats were divided into postnatal 0.5-, 1-, 2- and 3-month groups (n = 12). Spontaneous excitatory postsynaptic currents (sEPSCs) and field excitatory postsynaptic potentials (fEPSPs) mediated by AMPA receptors were recorded to evaluate the changes in the intrinsic membrane properties of hippocampal CA1 pyramidal neurons by using patch-clamp and MED64 planar microelectrode array technique respectively. The results showed that, during the period of postnatal 0.5-3 months, some of the intrinsic membrane properties of hippocampal CA1 pyramidal neurons, such as the membrane capacitance (Cm) and the resting membrane potential (RMP), showed no significant changes, while the membrane input resistance (Rin) and the time constant (τ) of the cells were decreased significantly. The amplitude, frequency and kinetics (both rise and decay times) of sEPSCs were significantly increased during the period of postnatal 0.5-1 month, but they were all decreased during the period of postnatal 1-3 months. In addition, the range of evoked fEPSPs in hippocamal CA1 region was significantly expanded, but the fEPSP amplitudes were decreased significantly during the period of postnatal 0.5-3 months. Furthermore, the evoked fEPSPs could be significantly inhibited by extracellular application of the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). These results suggest that AMPA receptor may act as a major type of excitatory receptor to regulate synaptic transmission and connections during the early stage of hippocampal postnatal development, which promotes the development and functional maturation of hippocampus in rats.

Pre- and Postnatal Parental Smoking and Acute Otitis Media in Early Childhood

PubMed Central

Håberg, Siri E.; Bentdal, Yngvild E.; London, Stephanie J.; Kværner, Kari J.; Nystad, Wenche; Nafstad, Per

2010-01-01

Aim To explore associations between acute otitis media in early childhood and prenatal and postnatal tobacco smoke exposure. Methods Subjects were 32,077 children born 2000 – 2005 in the Norwegian Mother and Child Study with questionnaire data on tobacco smoke exposure and acute otitis media up to 18 months of age. Multivariate regression models were used to obtain adjusted relative risks for acute otitis media. Results Acute otitis media was slightly more common in children exposed to parental smoking. The incidence from 0–6 months was 4.7% in unexposed children, and 6.0% in children exposed both pre-and postnatally. After adjusting for postnatal exposure and covariates, the relative risk for acute otitis media 0–6 months when exposed to maternal smoking in pregnancy was 1.34, 95% confidence interval: 1.06–1.69. Maternal smoking in pregnancy was associated with acute otitis media up to 12 months of age. Compared to non-exposed children, there was a slightly increased risk of recurrent acute otitis media for children exposed both pre- and postnatally with a relative risk of 1.24, 95% confidence interval: 1.01–1.52,. Conclusion Even in a cohort with relatively low exposure levels of parental smoking, maternal smoking in pregnancy was associated with an increased risk of acute otitis media in early childhood. PMID:19764924

Adult Neuropsychological Performance Following Prenatal and Early Postnatal Exposure to Tetrachloroethylene (PCE)-contaminated Drinking Water

PubMed Central

Janulewicz, Patricia A; White, Roberta F; Martin, Brett M; Winter, Michael R; Weinberg, Janice M; Vieira, Veronica; Aschengrau, Ann

2012-01-01

This population-based retrospective cohort study examined adult performance on a battery of neuropsychological tests in relation to prenatal and early postnatal exposure to tetrachloroethylene (PCE)-contaminated drinking water on Cape Cod, Massachusetts. Subjects were identified through birth records from 1969 through 1983. Exposure was modeled using pipe network information from town water departments, a PCE leaching and transport algorithm, EPANet water flow modeling software, and a Geographic Information System (GIS). Results of crude and multivariate analyses among 35 exposed and 28 unexposed subjects showed no association between prenatal and early postnatal exposure and decrements on tests that assess abilities in the domains of omnibus intelligence, academic achievement or language. The results were suggestive of an association between prenatal and early postnatal PCE exposure and diminished performance on tests that assessed abilities in the domains of visuospatial functioning, learning and memory, motor, attention and mood. Because the sample size was small, most findings were not statistically significant. Future studies with larger sample sizes should be conducted to further define the neuropsychological consequences of early developmental PCE exposure. PMID:22522125

Bisphenol A Increases Mammary Cancer Risk in Two Distinct Mouse Models of Breast Cancer1

PubMed Central

Weber Lozada, Kristen; Keri, Ruth A.

2011-01-01

Bisphenol A (BPA) is an industrial plasticizer that leaches from food containers during normal usage, leading to human exposure. Early and chronic exposure to endocrine-disrupting environmental contaminants such as BPA elevates the potential for long-term health consequences. We examined the impact of BPA exposure on fetal programming of mammary tumor susceptibility as well as its growth promoting effects on transformed breast cancer cells in vivo. Fetal mice were exposed to 0, 25, or 250 μg/kg BPA by oral gavage of pregnant dams. Offspring were subsequently treated with the known mammary carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA). While no significant differences in postnatal mammary development were observed, both low- and high-dose BPA cohorts had a statistically significant increase in susceptibility to DMBA-induced tumors compared to vehicle-treated controls. To determine if BPA also promotes established tumor growth, MCF-7 human breast cancer cells were subcutaneously injected into flanks of ovariectomized NCR nu/nu female mice treated with BPA, 17beta-estradiol, or placebo alone or combined with tamoxifen. Both estradiol- and BPA-treated cohorts formed tumors by 7 wk post-transplantation, while no tumors were detected in the placebo cohort. Tamoxifen reversed the effects of estradiol and BPA. We conclude that BPA may increase mammary tumorigenesis through at least two mechanisms: molecular alteration of fetal glands without associated morphological changes and direct promotion of estrogen-dependent tumor cell growth. Both results indicate that exposure to BPA during various biological states increases the risk of developing mammary cancer in mice. PMID:21636739

Profiling analysis of long non-coding RNAs in early postnatal mouse hearts

PubMed Central

Sun, Xiongshan; Han, Qi; Luo, Hongqin; Pan, Xiaodong; Ji, Yan; Yang, Yao; Chen, Hanying; Wang, Fangjie; Lai, Wenjing; Guan, Xiao; Zhang, Qi; Tang, Yuan; Chu, Jianhong; Yu, Jianhua; Shou, Weinian; Deng, Youcai; Li, Xiaohui

2017-01-01

Mammalian cardiomyocytes undergo a critical hyperplastic-to-hypertrophic growth transition at early postnatal age, which is important in establishing normal physiological function of postnatal hearts. In the current study, we intended to explore the role of long non-coding (lnc) RNAs in this transitional stage. We analyzed lncRNA expression profiles in mouse hearts at postnatal day (P) 1, P7 and P28 via microarray. We identified 1,146 differentially expressed lncRNAs with more than 2.0-fold change when compared the expression profiles of P1 to P7, P1 to P28, and P7 to P28. The neighboring genes of these differentially expressed lncRNAs were mainly involved in DNA replication-associated biological processes. We were particularly interested in one novel cardiac-enriched lncRNA, ENSMUST00000117266, whose expression was dramatically down-regulated from P1 to P28 and was also sensitive to hypoxia, paraquat, and myocardial infarction. Knockdown ENSMUST00000117266 led to a significant increase of neonatal mouse cardiomyocytes in G0/G1 phase and reduction in G2/M phase, suggesting that ENSMUST00000117266 is involved in regulating cardiomyocyte proliferative activity and is likely associated with hyperplastic-to-hypertrophic growth transition. In conclusion, our data have identified a large group of lncRNAs presented in the early postnatal mouse heart. Some of these lncRNAs may have important functions in cardiac hyperplastic-to-hypertrophic growth transition. PMID:28266538

Screening of miRNA profiles and construction of regulation networks in early and late lactation of dairy goat mammary glands.

PubMed

Ji, Zhibin; Liu, Zhaohua; Chao, Tianle; Hou, Lei; Fan, Rui; He, Rongyan; Wang, Guizhi; Wang, Jianmin

2017-09-20

In recent years, studies related to the expression profiles of miRNAs in the dairy goat mammary gland were performed, but regulatory mechanisms in the physiological environment and the dynamic homeostasis of mammary gland development and lactation are not clear. In the present study, sequencing data analysis of early and late lactation uncovered a total of 1,487 unique miRNAs, including 45 novel miRNA candidates and 1,442 known and conserved miRNAs, of which 758 miRNAs were co-expressed and 378 differentially expressed with P < 0.05. Moreover, 76 non-redundant target genes were annotated in 347 GO consortiums, with 3,143 candidate target genes grouped into 33 pathways. Additionally, 18 predicted target genes of 214 miRNAs were directly annotated in mammary gland development and used to construct regulatory networks based on GO annotation and the KEGG pathway. The expression levels of seven known miRNAs and three novel miRNAs were examined using quantitative real-time PCR. The results showed that miRNAs might play important roles in early and late lactation during dairy goat mammary gland development, which will be helpful to obtain a better understanding of the genetic control of mammary gland lactation and development.

Early postnatal treatment with clomipramine induces female sexual behavior and estrous cycle impairment.

PubMed

Molina-Jiménez, Tania; Limón-Morales, Ofelia; Bonilla-Jaime, Herlinda

2018-03-01

Administration of clomipramine (CMI), a tricyclic antidepressant, in early stages of development in rats, is considered an animal model for the study of depression. This pharmacological manipulation has induced behavioral and physiological alterations, i.e., less pleasure-seeking behaviors, despair, hyperactivity, cognitive dysfunction, alterations in neurotransmitter systems and in HPA axis. These abnormalities in adult male rats are similar to the symptoms observed in major depressive disorders. One of the main pleasure-seeking behaviors affected in male rats treated with CMI is sexual behavior. However, to date, no effects of early postnatal CMI treatment have been reported on female reproductive cyclicity and sexual behavior. Therefore, we explored CMI administration in early life (8-21 PN) on the estrous cycle and sexual behavior of adult female rats. Compared to the rats in the early postnatal saline treatment (CTRL group), the CMI rats had fewer estrous cycles, fewer days in the estrous stage, and longer cycles during a 20-day period of vaginal cytology analysis. On the behavioral test, the CMI rats displayed fewer proceptive behaviors (hopping, darting) and had lower lordosis quotients. Also, they usually failed to display lordosis and only rarely manifested marginal or normal lordosis. In contrast, the CTRL rats tended to display normal lordosis. These results suggest that early postnatal CMI treatment caused long-term disruptions of the estrous cycle and female sexual behavior, perhaps by alteration in the hypothalamic-pituitary-gonadal (HPG) axes and in neuronal circuits involved in the regulation of the performance and motivational of sexual behavior as the noradrenergic and serotonergic systems. Copyright © 2018 Elsevier Inc. All rights reserved.

Prenatal and early postnatal depression and child maltreatment among Japanese fathers.

PubMed

Takehara, Kenji; Suto, Maiko; Kakee, Naoko; Tachibana, Yoshiyuki; Mori, Rintaro

2017-08-01

We investigated the association of paternal depression in the prenatal and early postnatal period with child maltreatment tendency at two months postpartum among Japanese fathers. This population-based longitudinal study recruited Japanese perinatal women and their partners living in Nishio City, Aichi, Japan. Of the 270 fathers who participated, 196 were included in the analysis. All data were collected via self-administrated questionnaires at four time points: 20 weeks' gestation and in the first few days, one month, and two months postpartum. Paternal depression was assessed using the Edinburgh Postnatal Depression Scale. Three definitions of paternal depression were coded based on participants' scores on this measure: prenatal, prior, and current. Child maltreatment tendency was evaluated using the Child Maltreatment Scale at two months postpartum. The associations of the three definitions of paternal depression and child maltreatment tendency were separately analyzed using logistic regression analysis. The prevalence of prenatal, prior, and current paternal depression was 9.7%, 10.2%, and 8.8%, respectively. According to the multivariate analysis, current paternal depression was significantly associated with child maltreatment tendency at two months postpartum (adjusted odds ratio: 7.77, 95% CI: 1.83-33.02). The other two types of depression, however, were not related to child maltreatment tendency. Thus, current paternal depression increased the risk of child maltreatment tendency in the postnatal period, suggesting that early detection and treatment of paternal depression might be useful for the prevention of child maltreatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Early postnatal ozone exposure alters rat nodose and jugular sensory neuron development

PubMed Central

Zellner, Leor C.; Brundage, Kathleen M.; Hunter, Dawn D.; Dey, Richard D.

2011-01-01

Sensory neurons originating in nodose and jugular ganglia that innervate airway epithelium (airway neurons) play a role in inflammation observed following exposure to inhaled environmental irritants such as ozone (O3). Airway neurons can mediate airway inflammation through the release of the neuropeptide substance P (SP). While susceptibility to airway irritants is increased in early life, the developmental dynamics of afferent airway neurons are not well characterized. The hypothesis of this study was that airway neuron number might increase with increasing age, and that an acute, early postnatal O3 exposure might increase both the number of sensory airway neurons as well as the number SP-containing airway neurons. Studies using Fischer 344 rat pups were conducted to determine if age or acute O3 exposure might alter airway neuron number. Airway neurons in nodose and jugular ganglia were retrogradely labeled, removed, dissociated, and counted by means of a novel technique employing flow cytometry. In Study 1, neuron counts were conducted on postnatal days (PD) 6, 10, 15, 21, and 28. Numbers of total and airway neurons increased significantly between PD6 and PD10, then generally stabilized. In Study 2, animals were exposed to O3 (2 ppm) or filtered air (FA) on PD5 and neurons were counted on PD10, 15, 21, and 28. O3-exposed animals displayed significantly less total neurons on PD21 than FA controls. This study shows that age-related changes in neuron number occur, and that an acute, early postnatal O3 exposure significantly alters sensory neuron development. PMID:22140294

Prenatal Exposure to Respiratory Syncytial Virus Alters Postnatal Immunity and Airway Smooth Muscle Contractility during Early-Life Reinfections

PubMed Central

Harford, Terri J.; Agrawal, Vandana; Yen-Lieberman, Belinda; Rezaee, Fariba; Piedimonte, Giovanni

2017-01-01

Maternal viral infections can have pathological effects on the developing fetus which last long after birth. Recently, maternal-fetal transmission of respiratory syncytial virus (RSV) was shown to cause postnatal airway hyperreactivity (AHR) during primary early-life reinfection; however, the influence of prenatal exposure to RSV on offspring airway immunity and smooth muscle contractility during recurrent postnatal reinfections remains unknown. Therefore, we sought to determine whether maternal RSV infection impairs specific aspects of cell-mediated offspring immunity during early-life reinfections and the mechanisms leading to AHR. Red fluorescent protein-expressing recombinant RSV (rrRSV) was inoculated into pregnant rat dams at midterm, followed by primary and secondary postnatal rrRSV inoculations of their offspring at early-life time points. Pups and weanlings were tested for specific lower airway leukocyte populations by flow cytometry; serum cytokine/chemokine concentrations by multiplex ELISA and neurotrophins concentrations by standard ELISA; and ex vivo lower airway smooth muscle (ASM) contraction by physiological tissue bath. Pups born to RSV-infected mothers displayed elevated total CD3+ T cells largely lacking CD4+ and CD8+ surface expression after both primary and secondary postnatal rrRSV infection. Cytokine/chemokine analyses revealed reduced IFN-γ, IL-2, IL-12, IL-17A, IL-18, and TNF-α, as well as elevated nerve growth factor (NGF) expression. Prenatal exposure to RSV also increased ASM reactivity and contractility during early-life rrRSV infection compared to non-exposed controls. We conclude that maternal RSV infection can predispose offspring to postnatal lower airways dysfunction by altering immunity development, NGF signaling, and ASM contraction during early-life RSV reinfections. PMID:28178290

Factors associated with early resumption of sexual intercourse among postnatal women in Uganda.

PubMed

Alum, Alice C; Kizza, Irene B; Osingada, Charles P; Katende, Godfrey; Kaye, Dan K

2015-11-19

Despite being a key component to be addressed during postnatal period, sexuality has long been a subject of secrecy and taboo in Africa. Resumption of sexual intercourse after giving birth has been shown to reduce extramarital affairs and consequently reduce risk of sexually transmitted infections like HIV/AIDS. Consequences of early resumption of sexual intercourse include unwanted pregnancy, genital trauma and puerperal infection. The objective of the study was to assess prevalence and factors associated with early resumption of sexual intercourse among postnatal mothers attending postnatal clinic at a National referral Hospital in Uganda. A cross-sectional study that employed an interviewer-administered questionnaire was conducted among 374 women who delivered six months prior to conducting the study. The independent variables included socio-demographic characteristics of the participant, socio-demographic characteristics of the spouse, perceived cultural norms, medical history, mode of delivery, and postpartum complications. The dependent variable was timing of resumption of sexual intercourse after childbirth (before or after six weeks postpartum). Data were analysed using SPSS version 16.0. The study showed that 105 participants (21.6%) had resumed sexual intercourse before 6 weeks after childbirth. The participants' education level, occupation, and parity; education level of the spouse, age of baby and use of family planning were the factors associated with early resumption of sexual intercourse after child birth (before six weeks postpartum) (p < 0.05). Many women resumed sexual intercourse after six weeks. Women with high income, low parity, who ever-used contraception or had a spouse with high education level were more likely to have early resumption of sexual intercourse.

Expression of glucocorticoid receptor and early growth response gene 1 during postnatal development of two inbred strains of mice exposed to early life stress.

PubMed

Navailles, Sylvia; Zimnisky, Ross; Schmauss, Claudia

2010-07-01

Early life stress can elicit profound changes in adult gene expression and behavior. One consequence of early life stress is a decreased expression of glucocorticoid receptors (GRs) in the frontal cortex and hippocampus. However, neither the time of onset nor the mechanism(s) leading to decreased GR expression during postnatal development are known. The present study used two inbred strains of mice that differ in their behavioral responsiveness to stress (Balb/c and C57Bl/6), exposed them to an established paradigm of early life stress (infant maternal separation), and measured their expression of frontal cortical and hippocampal GRs and the putative transcriptional activator of the GR gene, early growth response gene (egr)-1, at defined stages of postnatal development. In both strains, real-time RT-PCR experiments revealed that decreased expression of GR in adolescence and adulthood is, in fact, preceded by increased GR expression during early life stress exposure. Thus, the early life stress-induced disruption of the normal stress-hyporesponsive period during infancy is accompanied by increased GR expression. Moreover, chronic treatment with the antidepressant drug fluoxetine during adolescence or adulthood reversed the effect of early life stress on adult GR mRNA expression. In contrast to the strain-independent effect of early life stress on GR expression, however, changes in egr-1 expression occurred only in Balb/c mice, and unlike the biphasic developmental changes in GR mRNA expression, egr-1 mRNA was decreased throughout postnatal development. Moreover, there was no consistent overlap of anatomic regions affected by decreased GR and egr-1 protein expression. Thus, in Balb/c mice, changes in GR and egr-1 expression can independently contribute to the phenotypes resulting from early life stress exposure. These findings illustrate that the impact of early life stress on gene expression changes is modulated by the genetic background and that the persistent

High uptake of exclusive breastfeeding and reduced early post-natal HIV transmission.

PubMed

Kuhn, Louise; Sinkala, Moses; Kankasa, Chipepo; Semrau, Katherine; Kasonde, Prisca; Scott, Nancy; Mwiya, Mwiya; Vwalika, Cheswa; Walter, Jan; Tsai, Wei-Yann; Aldrovandi, Grace M; Thea, Donald M

2007-12-26

Empirical data showing the clear benefits of exclusive breastfeeding (EBF) for HIV prevention are needed to encourage implementation of lactation support programs for HIV-infected women in low resource settings among whom replacement feeding is unsafe. We conducted a prospective, observational study in Lusaka, Zambia, to test the hypothesis that EBF is associated with a lower risk of postnatal HIV transmission than non-EBF. As part of a randomized trial of early weaning, 958 HIV-infected women and their infants were recruited and all were encouraged to breastfeed exclusively to 4 months. Single-dose nevirapine was provided to prevent transmission. Regular samples were collected from infants to 24 months of age and tested by PCR. Detailed measurements of actual feeding behaviors were collected to examine, in an observational analysis, associations between feeding practices and postnatal HIV transmission. Uptake of EBF was high with 84% of women reporting only EBF cumulatively to 4 months. Post-natal HIV transmission before 4 months was significantly lower (p = 0.004) among EBF (0.040 95% CI: 0.024-0.055) than non-EBF infants (0.102 95% CI: 0.047-0.157); time-dependent Relative Hazard (RH) of transmission due to non-EBF = 3.48 (95% CI: 1.71-7.08). There were no significant differences in the severity of disease between EBF and non-EBF mothers and the association remained significant (RH = 2.68 95% CI: 1.28-5.62) after adjusting for maternal CD4 count, plasma viral load, syphilis screening results and low birth weight. Non-EBF more than doubles the risk of early postnatal HIV transmission. Programs to support EBF should be expanded universally in low resource settings. EBF is an affordable, feasible, acceptable, safe and sustainable practice that also reduces HIV transmission providing HIV-infected women with a means to protect their children's lives. ClinicalTrials.gov NCT00310726.

Global gene expression and morphological alterations in the mammary gland after gestational exposure to bisphenol A, genistein and indole-3-carbinol in female Sprague-Dawley offspring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grassi, Tony F.

This study aimed to evaluate the modifying effects of dietary genistein (GEN) and indole-3-carbinol (I3C) on early mammary gland development in female Sprague-Dawley offspring born to mothers exposed to BPA during gestation. Pregnant rats were treated with BPA25 or 250 μg/kg bw/day from gestational days 10 to 21 with or without dietary intake of GEN (250 mg/kg chow) or I3C (2000 mg/kg chow). At post-natal day (PND) 21, female offspring from different litters were euthanized for mammary gland development and gene expression analyses. Our results indicated that prenatal exposure to BPA25 and 250 did not modify the ductal elongation ofmore » the mammary gland tree or the estrogen receptor alpha (ER-α) expression in terminal end buds (TEBs). However, BPA25-exposed offspring had a higher number of terminal structures (TEBs + TDs) and an increased mammary branching and cell proliferation index in TEBs. Besides that, BPA25 and 250 modulated the expression of several genes in the immature mammary gland that were not changed in a dose dependent manner and involved different clusters of up- and down-regulated genes. Furthermore, BPA25 and BPA250 + I3C-treated groups also had a higher number of enriched functional gene categories. In addition, maternal dietary GEN and I3C in association with BPA exposure produced specific gene expression alterations in the mammary gland and overcome the adverse effect of BPA25, decreasing the branching of the mammary gland. In conclusion, prenatal BPA exposure induced both morphological and gene expression modifications on the mammary gland that dietary intake of GEN and I3C reverted on BPA25-exposed animals. - Highlights: • Gestational BPA and its association with GEN and I3C modify gene expression on the early mammary gland development. • GEN and I3C induced a different gene expression signature than lower BPA dose. • Dietary GEN and I3C countered the adverse effect of lower BPA dose on the cell proliferation and mammary gland

Oligodendrocytes as Regulators of Neuronal Networks during Early Postnatal Development

PubMed Central

Ramos, Maria; Ikrar, Taruna; Kinoshita, Chisato; De Mei, Claudia; Tirotta, Emanuele; Xu, Xiangmin; Borrelli, Emiliana

2011-01-01

Oligodendrocytes are the glial cells responsible for myelin formation. Myelination occurs during the first postnatal weeks and, in rodents, is completed during the third week after birth. Myelin ensures the fast conduction of the nerve impulse; in the adult, myelin proteins have an inhibitory role on axon growth and regeneration after injury. During brain development, oligodendrocytes precursors originating in multiple locations along the antero-posterior axis actively proliferate and migrate to colonize the whole brain. Whether the initial interactions between oligodendrocytes and neurons might play a functional role before the onset of myelination is still not completely elucidated. In this article, we addressed this question by transgenically targeted ablation of proliferating oligodendrocytes during cerebellum development. Interestingly, we show that depletion of oligodendrocytes at postnatal day 1 (P1) profoundly affects the establishment of cerebellar circuitries. We observed an impressive deregulation in the expression of molecules involved in axon growth, guidance and synaptic plasticity. These effects were accompanied by an outstanding increase of neurofilament staining observed 4 hours after the beginning of the ablation protocol, likely dependent from sprouting of cerebellar fibers. Oligodendrocyte ablation modifies localization and function of ionotropic glutamate receptors in Purkinje neurons. These results show a novel oligodendrocyte function expressed during early postnatal brain development, where these cells participate in the formation of cerebellar circuitries, and influence its development. PMID:21589880

The effect of early postnatal discharge from hospital for women and infants: a systematic review protocol.

PubMed

Jones, Eleanor; Taylor, Beck; MacArthur, Christine; Pritchett, Ruth; Cummins, Carole

2016-02-08

The length of postnatal hospital stay has declined over the last 40 years. There is little evidence to support a policy of early discharge following birth, and there is some concern about whether early discharge of mothers and babies is safe. The Cochrane review on the effects of early discharge from hospital only included randomised controlled trials (RCTs) which are problematic in this area, and a systematic review including other study designs is required. The aim of this broader systematic review is to determine possible effects of a policy of early postnatal discharge on important maternal and infant health-related outcomes. A systematic search of published literature will be conducted for randomised controlled trials, non-randomised controlled trials (NRCTs), controlled before-after studies (CBA), and interrupted time series studies (ITS) that report on the effect of a policy of early postnatal discharge from hospital. Databases including Cochrane CENTRAL, MEDLINE, EMBASE, CINAHL and Science Citation Index will be searched for relevant material. Reference lists of articles will also be searched in addition to searches to identify grey literature. Screening of identified articles and data extraction will be conducted in duplicate and independently. Methodological quality of the included studies will be assessed using the Effective Practice and Organisation of Care (EPOC) criteria for risk of bias tool. Discrepancies will be resolved by consensus or by consulting a third author. Meta-analysis using a random effects model will be used to combine data. Where significant heterogeneity is present, data will be combined in a narrative synthesis. The findings will be reported according to the preferred reporting items for systematic reviews (PRISMA) statement. Information on the effects of early postnatal discharge from hospital will be important for policy makers and clinicians providing maternity care. This review will also identify any gaps in the current

Stress exposure in early post-natal life reduces telomere length: an experimental demonstration in a long-lived seabird

PubMed Central

Herborn, Katherine A.; Heidinger, Britt J.; Boner, Winnie; Noguera, Jose C.; Adam, Aileen; Daunt, Francis; Monaghan, Pat

2014-01-01

Exposure to stressors early in life is associated with faster ageing and reduced longevity. One important mechanism that could underlie these late life effects is increased telomere loss. Telomere length in early post-natal life is an important predictor of subsequent lifespan, but the factors underpinning its variability are poorly understood. Recent human studies have linked stress exposure to increased telomere loss. These studies have of necessity been non-experimental and are consequently subjected to several confounding factors; also, being based on leucocyte populations, where cell composition is variable and some telomere restoration can occur, the extent to which these effects extend beyond the immune system has been questioned. In this study, we experimentally manipulated stress exposure early in post-natal life in nestling European shags (Phalacrocorax aristotelis) in the wild and examined the effect on telomere length in erythrocytes. Our results show that greater stress exposure during early post-natal life increases telomere loss at this life-history stage, and that such an effect is not confined to immune cells. The delayed effects of increased telomere attrition in early life could therefore give rise to a ‘time bomb’ that reduces longevity in the absence of any obvious phenotypic consequences early in life. PMID:24648221

Maternal high fat diet promotion of mammary tumor risk in adult progeny is associated with early expansion of mammary cancer stem-like cells and increased maternal oxidative environment

USDA-ARS?s Scientific Manuscript database

Many adult chronic diseases might be programmed during early life by maternal nutritional history. Here, we evaluated effects of maternal high fat diet on mammary gland development and tumor formation in adult progeny. Female Wnt-1 transgenic mice exposed to high fat (HFD, 45% kcal fat) or control C...

Intervention among new parents followed up by an interview study exploring their experiences of telemedicine after early postnatal discharge.

PubMed

Danbjørg, D B; Wagner, L; Kristensen, B R; Clemensen, J

2015-06-01

a move towards earlier postnatal discharge raises the challenge of finding new ways to support families when they are discharged early after childbirth. to explore how postnatal parents experienced the use of telemedicine following early discharge from hospital (i.e. 24 hours after childbirth) by investigating if they consider that their postnatal needs are met, and whether or not they experience a sense of security and parental self-efficacy. intervention followed by a qualitative interview study. The intervention took place on a postnatal ward with approximately 1000 births a year. An app including chat, a knowledgebase and automated messages was trialled between postnatal parents at home and the hospital. Parents had access to the app for seven days after discharge. 42 new mothers were recruited from the postnatal ward in accordance with the inclusion criteria (i.e. discharged within 24 hours of childbirth). Both parents were invited for interview. 42 sets of parents participated in the trial, and 28 sets agreed to be interviewed. Interviews (n=28) were conducted with 27 mothers and 11 fathers. Parents were interviewed together in 10 cases, 17 mothers were interviewed alone, and one father was interviewed alone. The data analysis was inspired by systematic text condensation based on Giorgi׳s descriptive phenomenological method. parents were confident in use of the app, and did not experience any barriers in contacting the nurses via asynchronous communication. Parents received timely information and guidance by communicating online, and felt that their follow-up support needs were met. parents viewed the app as a lifeline, and saw it as a means of informing and guiding them following early discharge from hospital after childbirth. As such, this app shows potential for enhancing self-efficacy and postnatal sense of security. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mammary cell-activating factor regulates the hormone-independent transcription of the early lactation protein (ELP) gene in a marsupial.

PubMed

Pharo, Elizabeth A; Renfree, Marilyn B; Cane, Kylie N

2016-11-15

The regulation of the tammar wallaby (Macropus eugenii) early lactation protein (ELP) gene is complex. ELP is responsive to the lactogenic hormones; insulin (I), hydrocortisone (HC) and prolactin (PRL) in mammary gland explants but could not be induced with lactogenic hormones in tammar primary mammary gland cells, nor in KIM-2 conditionally immortalised murine mammary epithelial cells. Similarly, ELP promoter constructs transiently-transfected into human embryonic kidney (HEK293T) cells constitutively expressing the prolactin receptor (PRLR) and Signal Transducer and Activator of Transcription (STAT)5A were unresponsive to prolactin, unlike the rat and mouse β-casein (CSN2) promoter constructs. Identification of the minimal promoter required for the hormone-independent transcription of tammar ELP in HEK293Ts and comparative analysis of the proximal promoters of marsupial ELP and the orthologous eutherian colostrum trypsin inhibitor (CTI) gene suggests that mammary cell-activating factor (MAF), an E26 transformation-specific (ETS) factor, may bind to an AGGAAG motif and activate tammar ELP. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Melamine in prenatal and postnatal organs in rats.

PubMed

Chu, Ching Yan; Chu, Kai On; Ho, Chung Shun; Kwok, Sung Shing; Chan, Ho Ming; Fung, Kwok Pui; Wang, Chi Chiu

2013-01-01

Melamine can be transferred to fetus in utero through placenta and to infant ex utero by breast feeding. In this study, we characterized the pharmacokinetics of melamine in prenatal and postnatal organs in rats. Single bolus of melamine was administered to pregnant rats at different gestational stages and to infants at different postnatal stages. Distribution of melamine in maternal serum was about 30% higher in late pregnancy than that in early pregnancy; and it was 2 folds higher in postnatal serum in early infants in young adulthood. Distribution of melamine in all postnatal organs was higher than that in prenatal organs. Postnatal kidneys in early infants had the highest maximum concentration and the lowest clearance of melamine than the other postnatal organs. It may relate to the high vulnerability to the toxicity of melamine in this population. Copyright © 2012 Elsevier Inc. All rights reserved.

Prenatal and Early Postnatal Diagnosis of Congenital Toxoplasmosis in a Setting With No Systematic Screening in Pregnancy.

PubMed

Stajner, Tijana; Bobic, Branko; Klun, Ivana; Nikolic, Aleksandra; Srbljanovic, Jelena; Uzelac, Aleksandra; Rajnpreht, Irena; Djurkovic-Djakovic, Olgica

2016-03-01

To determine the risk of congenital toxoplasmosis (CT) and provide early (pre- or postnatal) identification of cases of CT in the absence of systematic screening in pregnancy.I n the presented cross-sectional study, serological criteria were used to date Toxoplasma gondii infection versus conception in 80 pregnant women with fetal abnormalities or referred to as suspected of acute infection, and in 16 women after delivery of symptomatic neonates. A combination of serological, molecular (qPCR), and biological (bioassay) methods was used for prenatal and/or postnatal diagnosis of CT. Most (77.5%) pregnant women were examined in advanced pregnancy. Of all the examined seropositive women (n = 90), infection could not be ruled out to have occurred during pregnancy in 93.3%, of which the majority (69%) was dated to the periconceptual period. CT was diagnosed in 25 cases, of which 17 prenatally and 8 postnatally. Molecular diagnosis proved superior, but the diagnosis of CT based on bioassay in 7 instances and by Western blot in 2 neonates shows that other methods remain indispensable. In the absence of systematic screening in pregnancy, maternal infection is often diagnosed late, or even only when fetal/neonatal infection is suspected. In such situations, use of a complex algorithm involving a combination of serological, biological, and molecular methods allows for prenatal and/or early postnatal diagnosis of CT, but lacks the preventive capacity provided by early maternal treatment.

Prenatal and Early Postnatal Diagnosis of Congenital Toxoplasmosis in a Setting With No Systematic Screening in Pregnancy

PubMed Central

Stajner, Tijana; Bobic, Branko; Klun, Ivana; Nikolic, Aleksandra; Srbljanovic, Jelena; Uzelac, Aleksandra; Rajnpreht, Irena; Djurkovic-Djakovic, Olgica

2016-01-01

Abstract To determine the risk of congenital toxoplasmosis (CT) and provide early (pre- or postnatal) identification of cases of CT in the absence of systematic screening in pregnancy. In the presented cross-sectional study, serological criteria were used to date Toxoplasma gondii infection versus conception in 80 pregnant women with fetal abnormalities or referred to as suspected of acute infection, and in 16 women after delivery of symptomatic neonates. A combination of serological, molecular (qPCR), and biological (bioassay) methods was used for prenatal and/or postnatal diagnosis of CT. Most (77.5%) pregnant women were examined in advanced pregnancy. Of all the examined seropositive women (n = 90), infection could not be ruled out to have occurred during pregnancy in 93.3%, of which the majority (69%) was dated to the periconceptual period. CT was diagnosed in 25 cases, of which 17 prenatally and 8 postnatally. Molecular diagnosis proved superior, but the diagnosis of CT based on bioassay in 7 instances and by Western blot in 2 neonates shows that other methods remain indispensable. In the absence of systematic screening in pregnancy, maternal infection is often diagnosed late, or even only when fetal/neonatal infection is suspected. In such situations, use of a complex algorithm involving a combination of serological, biological, and molecular methods allows for prenatal and/or early postnatal diagnosis of CT, but lacks the preventive capacity provided by early maternal treatment. PMID:26945416

Early Postnatal Manganese Exposure Causes Lasting Impairment of Selective and Focused Attention and Arousal Regulation in Adult Rats.

PubMed

Beaudin, Stephane A; Strupp, Barbara J; Strawderman, Myla; Smith, Donald R

2017-02-01

Studies in children and adolescents have associated early developmental manganese (Mn) exposure with inattention, impulsivity, hyperactivity, and oppositional behaviors, but causal inferences are precluded by the correlational nature of the data and generally limited control for potential confounders. To determine whether early postnatal oral Mn exposure causes lasting attentional and impulse control deficits in adulthood, and whether continued lifelong Mn exposure exacerbates these effects, using a rat model of environmental Mn exposure. Neonates were exposed orally to 0, 25 or 50 mg Mn/kg/day during early postnatal life (PND 1-21) or throughout life from PND 1 until the end of the study. In adulthood, the animals were tested on a series of learning and attention tasks using the five-choice serial reaction time task. Early postnatal Mn exposure caused lasting attentional dysfunction due to impairments in attentional preparedness, selective attention, and arousal regulation, whereas associative ability (learning) and impulse control were spared. The presence and severity of these deficits varied with the dose and duration of Mn exposure. This study is the first to show that developmental Mn exposure can cause lasting impairments in focused and selective attention and arousal regulation, and to identify the specific nature of the impairments. Given the importance of attention and arousal regulation in cognitive functioning, these findings substantiate concerns about the adverse effects of developmental Mn exposure in humans. Citation: Beaudin SA, Strupp BJ, Strawderman M, Smith DR. 2017. Early postnatal manganese exposure causes lasting impairment of selective and focused attention and arousal regulation in adult rats. Environ Health Perspect 125:230-237; http://dx.doi.org/10.1289/EHP258.

Early Postnatal Manganese Exposure Causes Lasting Impairment of Selective and Focused Attention and Arousal Regulation in Adult Rats

PubMed Central

Beaudin, Stephane A.; Strupp, Barbara J.; Strawderman, Myla; Smith, Donald R.

2016-01-01

Background: Studies in children and adolescents have associated early developmental manganese (Mn) exposure with inattention, impulsivity, hyperactivity, and oppositional behaviors, but causal inferences are precluded by the correlational nature of the data and generally limited control for potential confounders. Objectives: To determine whether early postnatal oral Mn exposure causes lasting attentional and impulse control deficits in adulthood, and whether continued lifelong Mn exposure exacerbates these effects, using a rat model of environmental Mn exposure. Methods: Neonates were exposed orally to 0, 25 or 50 mg Mn/kg/day during early postnatal life (PND 1–21) or throughout life from PND 1 until the end of the study. In adulthood, the animals were tested on a series of learning and attention tasks using the five-choice serial reaction time task. Results: Early postnatal Mn exposure caused lasting attentional dysfunction due to impairments in attentional preparedness, selective attention, and arousal regulation, whereas associative ability (learning) and impulse control were spared. The presence and severity of these deficits varied with the dose and duration of Mn exposure. Conclusions: This study is the first to show that developmental Mn exposure can cause lasting impairments in focused and selective attention and arousal regulation, and to identify the specific nature of the impairments. Given the importance of attention and arousal regulation in cognitive functioning, these findings substantiate concerns about the adverse effects of developmental Mn exposure in humans. Citation: Beaudin SA, Strupp BJ, Strawderman M, Smith DR. 2017. Early postnatal manganese exposure causes lasting impairment of selective and focused attention and arousal regulation in adult rats. Environ Health Perspect 125:230–237; http://dx.doi.org/10.1289/EHP258 PMID:27384154

MEAL PARAMETERS AND VAGAL GASTROINTESTINAL AFFERENTS IN MICE THAT EXPERIENCED EARLY POSTNATAL OVERNUTRITION

PubMed Central

Biddinger, Jessica E.; Fox, Edward A.

2010-01-01

Early postnatal overnutrition results in a predisposition to develop obesity due in part to hypothalamic and sympathetic dysfunction. Potential involvement of another major regulatory system component - the vagus nerve - has not been examined. Moreover, feeding disturbances have rarely been investigated prior to development of obesity when confounds due to obesity are minimized. To examine these issues, litters were culled on the day of birth to create small litters (SL; overnutrition), or normal-size litters (NL; normal nutrition). Body weight, fat pad weight, meal patterns, and vagal sensory duodenal innervation were compared between SL and NL adult mice prior to development of obesity. Meal patterns were studied 18 hour/day for 3 weeks using a balanced diet. Then vagal mechanoreceptors were labeled using anterograde transport of wheatgerm agglutinin-horseradish peroxidase injected into the nodose ganglion and their density and morphology were examined. Between postnatal day 1 and weaning, body weight of SL mice was greater than for NL mice. By young adulthood it was similar in both groups, whereas SL fat pad weight was greater in males, suggesting postnatal overnutrition produced a predisposition to obesity. SL mice exhibited increased food intake, decreased satiety ratio, and increased first meal rate (following mild food deprivation) compared to NL mice, suggesting postnatal overnutrition disrupted satiety. The density and structure of intestinal IGLEs appeared similar in SL and NL mice. Thus, although a vagal role cannot be excluded, our meal parameter and anatomical findings provided no evidence for significant postnatal overnutrition effects on vagal gastrointestinal afferents. PMID:20403369

Meal parameters and vagal gastrointestinal afferents in mice that experienced early postnatal overnutrition.

PubMed

Biddinger, Jessica E; Fox, Edward A

2010-08-04

Early postnatal overnutrition results in a predisposition to develop obesity due in part to hypothalamic and sympathetic dysfunction. Potential involvement of another major regulatory system component--the vagus nerve--has not been examined. Moreover, feeding disturbances have rarely been investigated prior to development of obesity when confounds due to obesity are minimized. To examine these issues, litters were culled on the day of birth to create small litters (SL; overnutrition), or normal size litters (NL; normal nutrition). Body weight, fat pad weight, meal patterns, and vagal sensory duodenal innervation were compared between SL and NL adult mice prior to development of obesity. Meal patterns were studied 18 h/day for 3 weeks using a balanced diet. Then vagal mechanoreceptors were labeled using anterograde transport of wheatgerm agglutinin-horseradish peroxidase injected into the nodose ganglion and their density and morphology were examined. Between postnatal day 1 and weaning, body weight of SL mice was greater than for NL mice. By young adulthood it was similar in both groups, whereas SL fat pad weight was greater in males, suggesting postnatal overnutrition produced a predisposition to obesity. SL mice exhibited increased food intake, decreased satiety ratio, and increased first meal rate (following mild food deprivation) compared to NL mice, suggesting postnatal overnutrition disrupted satiety. The density and structure of intestinal IGLEs appeared similar in SL and NL mice. Thus, although a vagal role cannot be excluded, our meal parameter and anatomical findings provided no evidence for significant postnatal overnutrition effects on vagal gastrointestinal afferents. Copyright 2010 Elsevier Inc. All rights reserved.

Endocrine hormones and local signals during the development of the mouse mammary gland.

PubMed

Brisken, Cathrin; Ataca, Dalya

2015-01-01

Most of mammary gland development occurs postnatally under the control of female reproductive hormones, which in turn interact with other endocrine factors. While hormones impinge on many tissues and trigger very complex biological responses, tissue recombination experiments with hormone receptor-deficient mammary epithelia revealed eminent roles for estrogens, progesterone, and prolactin receptor (PrlR) signaling that are intrinsic to the mammary epithelium. A subset of the luminal mammary epithelial cells expresses the estrogen receptor α (ERα), the progesterone receptor (PR), and the PrlR and act as sensor cells. These cells convert the detected systemic signals into local signals that are developmental stage-dependent and may be direct, juxtacrine, or paracrine. This setup ensures that the original input is amplified and that the biological responses of multiple cell types can be coordinated. Some key mediators of hormone action have been identified such as Wnt, EGFR, IGFR, and RANK signaling. Multiple signaling pathways such as FGF, Hedgehog, and Notch signaling participate in driving different aspects of mammary gland development locally but how they link to the hormonal control remains to be elucidated. An increasing number of endocrine factors are appearing to have a role in mammary gland development, the adipose tissue is increasingly recognized to play a role in endocrine regulation, and a complex role of the immune system with multiple different cell types is being revealed. For further resources related to this article, please visit the WIREs website. © 2015 Wiley Periodicals, Inc.

Impaired GABAergic inhibition in the prefrontal cortex of early postnatal phencyclidine (PCP)-treated rats.

PubMed

Kjaerby, Celia; Broberg, Brian V; Kristiansen, Uffe; Dalby, Nils Ole

2014-09-01

A compromised γ-aminobutyric acid (GABA)ergic system is hypothesized to be part of the underlying pathophysiology of schizophrenia. N-methyl-D-aspartate (NMDA) receptor hypofunction during neurodevelopment is proposed to disrupt maturation of interneurons causing an impaired GABAergic transmission in adulthood. The present study examines prefrontal GABAergic transmission in adult rats administered with the NMDA receptor channel blocker, phencyclidine (PCP), for 3 days during the second postnatal week. Whole-cell patch-clamp recordings from pyramidal cells in PCP-treated rats showed a 22% reduction in the frequency of miniature inhibitory postsynaptic currents in layer II/III, but not in layer V pyramidal neurons of the prefrontal cortex. Furthermore, early postnatal PCP treatment caused insensitivity toward effects of the GABA transporter 1 (GAT-1) inhibitor, 1,2,5,6-tetrahydro-1-[2-[[(diphenyl-methylene)amino]oxy]ethyl]-3-pyridinecarboxylic acid, and also diminished currents passed by δ-subunit-containing GABAA receptors in layer II/III pyramidal neurons. The observed impairments in GABAergic function are compatible with the alteration of GABAergic markers as well as cognitive dysfunction observed in early postnatal PCP-treated rats and support the hypothesis that PCP administration during neurodevelopment affects the functionality of interneurons in later life. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Lactation stage-dependent expression of transporters in rat whole mammary gland and primary mammary epithelial organoids.

PubMed

Gilchrist, Samuel E; Alcorn, Jane

2010-04-01

Since solute carrier (SLC) and ATP-binding cassette (ABC) transporters play pivotal roles in the transport of both nutrients and drugs into breast milk, drug-nutrient transport interactions at the lactating mammary gland are possible. Our purpose was to characterize lactation stage-dependent changes in transporter expression in rat mammary gland and isolated mammary epithelial organoids (MEO) to provide additional insight for the safe use of maternal medications during breastfeeding. We used quantitative reverse transcription-polymerase chain reaction to assess the temporal expression patterns of SLC and ABC transporters in rat mammary gland and isolated MEO at different stages of lactation. In whole mammary gland five distinct patterns of expression emerged relative to late gestation: (i) decreasing throughout lactation (Mdr1a, Mdr1b, Mrp1, Octn2, Ent2, Ent3, Ncbt2, Mtx1); (ii) prominent increase in early lactation, which may remain elevated or decline with advancing lactation (Octn1, Cnt2, Cnt3, Ent1, Pept1, Pept2); (iii) constant but decreasing later in lactation (Octn3, Dmt1); (iv) increasing until mid-to-late lactation (Oct1, Cnt1); and (v) prominent increase late in lactation (Ncbt1). In isolated MEO (an enriched source of mammary epithelial cells) major differences in expression patterns were noted for Octn3, Ncbt1, and Mtx1, but otherwise were reasonably similar with the whole mammary gland. In conclusion our study augments existing data on transporter expression in the lactating mammary gland. These data should facilitate investigations into lactation-stage dependent changes in drug or nutrient milk-to-serum concentration ratios, the potential for drug- or disease-transporter interactions, and mechanistic studies of transporter function in the lactating mammary gland.

Intestinal microbiota influence the early postnatal development of the enteric nervous system.

PubMed

Collins, J; Borojevic, R; Verdu, E F; Huizinga, J D; Ratcliffe, E M

2014-01-01

Normal gastrointestinal function depends on an intact and coordinated enteric nervous system (ENS). While the ENS is formed during fetal life, plasticity persists in the postnatal period during which the gastrointestinal tract is colonized by bacteria. We tested the hypothesis that colonization of the bowel by intestinal microbiota influences the postnatal development of the ENS. The development of the ENS was studied in whole mount preparations of duodenum, jejunum, and ileum of specific pathogen-free (SPF), germ-free (GF), and altered Schaedler flora (ASF) NIH Swiss mice at postnatal day 3 (P3). The frequency and amplitude of circular muscle contractions were measured in intestinal segments using spatiotemporal mapping of video recorded spontaneous contractile activity with and without exposure to lidocaine and N-nitro-L-arginine (NOLA). Immunolabeling with antibodies to PGP9.5 revealed significant abnormalities in the myenteric plexi of GF jejunum and ileum, but not duodenum, characterized by a decrease in nerve density, a decrease in the number of neurons per ganglion, and an increase in the proportion of myenteric nitrergic neurons. Frequency of amplitude of muscle contractions were significantly decreased in the jejunum and ileum of GF mice and were unaffected by exposure to lidocaine, while NOLA enhanced contractile frequency in the GF jejunum and ileum. These findings suggest that early exposure to intestinal bacteria is essential for the postnatal development of the ENS in the mid to distal small intestine. Future studies are needed to investigate the mechanisms by which enteric microbiota interact with the developing ENS. © 2013 John Wiley & Sons Ltd.

Wnt proteins are self-renewal factors for mammary stem cells and promote their long-term expansion in culture.

PubMed

Zeng, Yi Arial; Nusse, Roel

2010-06-04

Adult stem cells have the ability to self-renew and to generate specialized cells. Self-renewal is dependent on extrinsic niche factors but few of those signals have been identified. In addition, stem cells tend to differentiate in the absence of the proper signals and are therefore difficult to maintain in cell culture. The mammary gland provides an excellent system to study self-renewal signals, because the organ develops postnatally, arises from stem cells, and is readily generated from transplanted cells. We show here that adult mammary glands contain a Wnt-responsive cell population that is enriched for stem cells. In addition, stem cells mutant for the negative-feedback regulator Axin2 and therefore sensitized to Wnt signals have a competitive advantage in mammary gland reconstitution assays. In cell culture experiments, exposure to purified Wnt protein clonally expands mammary stem cells for many generations and maintains their ability to generate functional glands in transplantation assays. We conclude that Wnt proteins serve as rate-limiting self-renewal signals acting directly on mammary stem cells. Copyright 2010 Elsevier Inc. All rights reserved.

[Formation of antioxidant defence system of geese in embryogenesis and early postnatal ontogenesis].

PubMed

Danchenko, O O; Kalytka, V V

2002-01-01

The features of antioxidant protection of tissues of a liver and blood of the gooses in embriogenesis and early postnatal ontogenesis are found out. Maximal contents TBA active products both in a liver, and in a blood are observed in 28 diurnal embriones. Is shown, that in a liver the activity of basic antioxidant enzymes (superoxide dismutases, catalase and glutathione peroxidase) in a liver is developed already at early stages embriogenesis and is considerably enlarged in the end embriogenesis. The becoming of enzymatic system of a blood descends much more slower.

Prenatal and Early Postnatal Exposure to Cigarette Smoke Decreases BDNF/TrkB Signaling and Increases Abnormal Behaviors Later in Life

PubMed Central

Xiao, Lan; Kish, Vincent L.; Benders, Katherine M.

2016-01-01

Background: Cigarette smoke exposure during prenatal and early postnatal periods increases the incidence of a variety of abnormal behaviors later in life. The purpose of this study was to identify the possible critical period of susceptibility to cigarette smoke exposure and evaluate the possibe effects of cigarette smoke during early life on brain-derived neurotrophic factor/neurotrophic tyrosine kinase receptor B signaling in the brain. Methods: Three different age of imprinting control region mice were exposed to cigarette smoke or filtered air for 10 consecutive days beginning on either gestational day 7 by maternal exposure, or postnatal days 2 or 21 by direct inhalation. A series of behavioral profiles and neurotrophins in brain were measured 24 hours after mice received acute restraint stress for 1 hour on postnatal day 59. Results: Cigarette smoke exposure in gestational day 7 and postnatal day 2 produced depression-like behaviors as evidenced by significantly increased immobility in both tail suspension and forced-swim test. Increased entry latencies, but not ambulation in the open field test, were also observed in the gestational day 7 and postnatal day 2 cigarette smoke exposure groups. Genetic analysis showed that gestational day 7 cigarette smoke exposure significantly altered mRNA level of brain-derived neurotrophic factor/tyrosine kinase receptor B in the hippocampus. However, behavioral profiles and brain-derived neurotrophic factor/tyrosine kinase receptor B signaling were not significantly changed in PND21 cigarette smoke exposure group compared with FA group. Conclusions: These results suggest that a critical period of susceptibility to cigarette smoke exposure exists in the prenatal and early postnatal period, which results a downregulation in brain-derived neurotrophic factor/tyrosine kinase receptor B signaling in the hippocampus and enhances depression-like behaviors later in life. PMID:26503133

Clinical presentation of postnatal and non-postnatal depressive episodes.

PubMed

Cooper, Carly; Jones, Lisa; Dunn, Emma; Forty, Liz; Haque, Sayeed; Oyebode, Femi; Craddock, Nick; Jones, Ian

2007-09-01

The relationship of postnatal (postpartum) depression (PND) to episodes of depression occurring at other times is not well understood. Despite a number of studies of clinical presentation, there is little consistency in the literature. We have undertaken within- and between-individual comparisons of the clinical presentation of postnatal (PN) and non-postnatal (NPN) depressive episodes in women with recurrent depression. In a sample of well-characterized, parous women meeting DSM-IV and ICD-10 criteria for recurrent major depressive disorder, the clinical presentation of episodes of major depression with onset within 4 weeks of giving birth (PND group, n=50) were compared with (i) the non-postnatal episodes of women with PND, and (ii) episodes of major depression in parous women who had not experienced episodes of mood disorder in relation to childbirth (NPND group, n=132). In addition, the non-postnatal episodes of the PND group of women were compared with the depressive episodes of the NPND group. The small number of differences found between PN and NPN depressive episodes, such as reduced early morning wakening in postnatal episodes, are likely to be explicable by the context of having a new baby rather than by any difference in the nature of the underlying depression. The results do not point to substantial differences in clinical presentation between episodes of major depression occurring in relation to childbirth and at other times. Other avenues of research are therefore required to demonstrate a specific relationship between childbirth and depression.

Epithelial Xbp1 Is Required for Cellular Proliferation and Differentiation during Mammary Gland Development

PubMed Central

Hasegawa, Daisuke; Calvo, Veronica; Avivar-Valderas, Alvaro; Lade, Abigale; Chou, Hsin-I; Lee, Youngmin A.; Farias, Eduardo F.; Aguirre-Ghiso, Julio A.

2015-01-01

Xbp1, a key mediator of the unfolded protein response (UPR), is activated by IRE1α-mediated splicing, which results in a frameshift to encode a protein with transcriptional activity. However, the direct function of Xbp1 in epithelial cells during mammary gland development is unknown. Here we report that the loss of Xbp1 in the mammary epithelium through targeted deletion leads to poor branching morphogenesis, impaired terminal end bud formation, and spontaneous stromal fibrosis during the adult virgin period. Additionally, epithelial Xbp1 deletion induces endoplasmic reticulum (ER) stress in the epithelium and dramatically inhibits epithelial proliferation and differentiation during lactation. The synthesis of milk and its major components, α/β-casein and whey acidic protein (WAP), is significantly reduced due to decreased prolactin receptor (Prlr) and ErbB4 expression in Xbp1-deficient mammary epithelium. Reduction of Prlr and ErbB4 expression and their diminished availability at the cell surface lead to reduced phosphorylated Stat5, an essential regulator of cell proliferation and differentiation during lactation. As a result, lactating mammary glands in these mice produce less milk protein, leading to poor pup growth and postnatal death. These findings suggest that the loss of Xbp1 induces a terminal UPR which blocks proliferation and differentiation during mammary gland development. PMID:25713103

Early-postnatal changes in adiposity and lipids profile by transgenerational developmental programming in swine with obesity/leptin resistance.

PubMed

Gonzalez-Bulnes, Antonio; Astiz, Susana; Ovilo, Cristina; Lopez-Bote, Clemente J; Sanchez-Sanchez, Raul; Perez-Solana, Maria L; Torres-Rovira, Laura; Ayuso, Miriam; Gonzalez, Jorge

2014-10-01

Maternal malnutrition during pregnancy, both deficiency and excess, induces changes in the intrauterine environment and the metabolic status of the offspring, playing a key role in the growth, status of fitness/obesity and appearance of metabolic disorders during postnatal life. There is increasing evidence that these effects may not be only limited to the first generation of descendants, the offspring directly exposed to metabolic challenges, but to subsequent generations. This study evaluated, in a swine model of obesity/leptin resistance, the existence and extent of transgenerational developmental programming effects. Pre- and postnatal development, adiposity and metabolic features were assessed in the second generation of piglets, descendant of sows exposed to either undernutrition or overnutrition during pregnancy. The results indicated that these piglets exhibited early-postnatal increases in adiposity and disturbances in lipid profiles compatible with the early prodrome of metabolic syndrome, with liver tissue also displaying evidence of paediatric liver disease. These features indicative of early-life metabolic disorders were more evident in the males that were descended from overfed grandmothers and during the transition from milk to solid feeding. Thus, this study provides evidence supporting transgenerational developmental programming and supports the necessity for the development of strategies for avoiding the current epidemics of childhood overweight and obesity. © 2014 Society for Endocrinology.

Update on Postnatal Steroids.

PubMed

Halliday, Henry L

2017-01-01

Antenatal steroid treatment to enhance fetal lung maturity and surfactant treatment to prevent or treat respiratory distress syndrome have been major advances in perinatal medicine in the past 40 years contributing to improved outcomes for preterm infants. Use of postnatal steroids to prevent or treat chronic lung disease in preterm infants has been less successful and associated with adverse neurodevelopmental outcomes. Although early (in the first week of life) postnatal steroid treatment facilitates earlier extubation and reduces the risk of chronic lung disease, it is associated with adverse effects, such as hyperglycemia, hypertension, gastrointestinal bleeding and perforation, hypertrophic cardiomyopathy, growth failure, and cerebral palsy, and cannot be recommended. Early treatment with hydrocortisone may also improve survival without chronic lung disease, but concerns remain about possible adverse effects such as gastrointestinal perforation and sepsis, particularly in very preterm infants. Early inhaled budesonide also reduces the incidence of chronic lung disease but there are concerns that this may occur at the expense of increased risk of death. More studies of early low-dose steroids with adequate long-term follow-up are needed before they can be recommended for the prevention of chronic lung disease. Late (after the first week of life) postnatal steroids may have a better benefit-to-harm ratio than early steroids. A Cochrane Review shows that late steroid treatment reduces chronic lung disease, the combination of death and chronic lung disease at both 28 days and 36 weeks' corrected age, and the need for later rescue dexamethasone. Adverse effects include hyperglycemia, hypertension, hypertrophic cardiomyopathy, and severe retinopathy of prematurity but without an increase in blindness. Long-term neurodevelopmental effects are not significantly increased by late postnatal steroid treatment. Current recommendations are that postnatal steroid treatment

Physiologically activated mammary fibroblasts promote postpartum mammary cancer

PubMed Central

Guo, Qiuchen; Burchard, Julja; Spellman, Paul

2017-01-01

Women diagnosed with breast cancer within 5 years of childbirth have poorer prognosis than nulliparous or pregnant women. Weaning-induced breast involution is implicated, as the collagen-rich, immunosuppressive microenvironment of the involuting mammary gland is tumor promotional in mice. To investigate the role of mammary fibroblasts, isolated mammary PDGFRα+ cells from nulliparous and postweaning mice were assessed for activation phenotype and protumorigenic function. Fibroblast activation during involution was evident by increased expression of fibrillar collagens, lysyl oxidase, Tgfb1, and Cxcl12 genes. The ability of mammary tumors to grow in an isogenic, orthotopic transplant model was increased when tumor cells were coinjected with involution-derived compared with nulliparous-derived mammary fibroblasts. Mammary tumors in the involution-fibroblast group had increased Ly6C+ monocytes at the tumor border, and decreased CD8+ T cell infiltration and tumor cell death. Ibuprofen treatment suppressed involution-fibroblast activation and tumor promotional capacity, concurrent with decreases in tumor Ly6C+ monocytes, and increases in intratumoral CD8+ T cell infiltration, granzyme levels, and tumor cell death. In total, our data identify a COX/prostaglandin E2 (PGE2)–dependent activated mammary fibroblast within the involuting mammary gland that displays protumorigenic, immunosuppressive activity, identifying fibroblasts as potential targets for the prevention and treatment of postpartum breast cancer. PMID:28352652

Intrauterine and early postnatal exposure to outdoor air pollution and lung function at preschool age.

PubMed

Morales, Eva; Garcia-Esteban, Raquel; de la Cruz, Oscar Asensio; Basterrechea, Mikel; Lertxundi, Aitana; de Dicastillo, Maria D Martinez López; Zabaleta, Carlos; Sunyer, Jordi

2015-01-01

Effects of prenatal and postnatal exposure to air pollution on lung function at preschool age remain unexplored. We examined the association of exposure to air pollution during specific trimesters of pregnancy and postnatal life with lung function in preschoolers. Lung function was assessed with spirometry in preschoolers aged 4.5 years (n=620) participating in the INfancia y Medio Ambiente (INMA) cohort. Temporally adjusted land use regression (LUR) models were applied to estimate individual residential exposures to benzene and nitrogen dioxide (NO₂) during specific trimesters of pregnancy and early postnatal life (the first year of life). Recent and current (1 year and 1 week before lung function testing, respectively) exposures to NO₂ and nitrogen oxides (NOx) were also assessed. Exposure to higher levels of benzene and NO₂ during pregnancy was associated with reduced lung function. FEV1 estimates for an IQR increase in exposures during the second trimester of pregnancy were -18.4 mL, 95% CI -34.8 to -2.1 for benzene and -28.0 mL, 95% CI -52.9 to -3.2 for NO₂. Relative risk (RR) of low lung function (<80% of predicted FEV1) for an IQR increase in benzene and NO₂ during the second trimester of pregnancy were 1.22, 95% CI 1.02 to 1.46 and 1.30, 95% CI 0.97 to 1.76, respectively. Associations for early postnatal, recent and current exposures were not statistically significant. Stronger associations appeared among allergic children and those of lower social class. Prenatal exposure to residential traffic-related air pollution may result in long-term lung function deficits at preschool age. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The impact of early postnatal environmental enrichment on maternal care and offspring behaviour following weaning.

PubMed

Li, Ki Angel; Lund, Emilie Torp; Voigt, Jörg-Peter W

2016-01-01

The early postnatal period is a sensitive period in rodents as behavioural systems are developing and maturing during this time. However, relatively little information is available about the impact of environmental enrichment on offspring behaviour if enrichment is implemented only during this period. Here, environmental enrichment was provided from postnatal day 1 until weaning. On post-natal day 9, maternal behaviour and nonmaternal behaviour of the dam was observed. Nursing time in the enriched group was reduced but dams showed more non-maternal appetitive behaviours. Offspring were exposed to either the open field or the elevated plus maze (EPM) after weaning. In the open field, rats from the enriched group approached the more aversive inner zone of the open field later than control rats. Offspring from the enriched group made fewer entries into the inner zone and spent less time in this part of the arena. Enrichment had no impact on behaviour in the EPM. The present study provides evidence that postnatal enrichment can interfere with maternal behaviour in rats and can possibly lead to increased anxiety in the offspring. The findings suggest that enrichment procedures can have potentially unintended effects, interfering with the development of emotional behaviours in rats. Copyright © 2015 Elsevier B.V. All rights reserved.

Mammary stem cells: angels or demons in mammary gland?

PubMed

Chen, Xueman; Liu, Qiang; Song, Erwei

2017-01-01

A highly dynamic development process exits within the epithelia of mammary gland, featuring morphogenetic variation during puberty, pregnancy, lactation, and regression. The identification of mammary stem cells (MaSCs) via lineage-tracing studies has substantiated a hierarchical organization of the mammary epithelia. A single MaSC is capable of reconstituting the entirely functional mammary gland upon orthotopic transplantation. Although different mammary cell subpopulations can be candidate cells-of-origin for distinct breast tumor subtypes, it still lacks experimental proofs whether MaSCs, the most primitive cells, are the 'seeds' of malignant transformation during most, if not all, tumorigenesis in the breast. Here, we review current knowledge of mammary epithelial hierarchy, highlighting the roles of mammary stem/progenitor cells and breast cancer stem cells (BCSCs) along with their key molecular regulators in organ development and cancer evolution. Clarifying these issues will pave the way for developing novel interventions toward stem/progenitor cells in either prevention or treatment of breast cancer (BrCa).

Mammary stem cells: angels or demons in mammary gland?

PubMed Central

Chen, Xueman; Liu, Qiang; Song, Erwei

2017-01-01

A highly dynamic development process exits within the epithelia of mammary gland, featuring morphogenetic variation during puberty, pregnancy, lactation, and regression. The identification of mammary stem cells (MaSCs) via lineage-tracing studies has substantiated a hierarchical organization of the mammary epithelia. A single MaSC is capable of reconstituting the entirely functional mammary gland upon orthotopic transplantation. Although different mammary cell subpopulations can be candidate cells-of-origin for distinct breast tumor subtypes, it still lacks experimental proofs whether MaSCs, the most primitive cells, are the ‘seeds’ of malignant transformation during most, if not all, tumorigenesis in the breast. Here, we review current knowledge of mammary epithelial hierarchy, highlighting the roles of mammary stem/progenitor cells and breast cancer stem cells (BCSCs) along with their key molecular regulators in organ development and cancer evolution. Clarifying these issues will pave the way for developing novel interventions toward stem/progenitor cells in either prevention or treatment of breast cancer (BrCa). PMID:29263909

Impairments in prehension produced by early postnatal sensory motor cortex activity blockade.

PubMed

Martin, J H; Donarummo, L; Hacking, A

2000-02-01

This study examined the effects of blocking neural activity in sensory motor cortex during early postnatal development on prehension. We infused muscimol, either unilaterally or bilaterally, into the sensory motor cortex of cats to block activity continuously between postnatal weeks 3-7. After stopping infusion, we trained animals to reach and grasp a cube of meat and tested behavior thereafter. Animals that had not received muscimol infusion (unilateral saline infusion; age-matched) reached for the meat accurately with small end-point errors. They grasped the meat using coordinated digit flexion followed by forearm supination on 82.7% of trials. Performance using either limb did not differ significantly. In animals receiving unilateral muscimol infusion, reaching and grasping using the limb ipsilateral to the infusion were similar to controls. The limb contralateral to infusion showed significant increases in systematic and variable reaching end-point errors, often requiring subsequent corrective movements to contact the meat. Grasping occurred on only 14.8% of trials, replaced on most trials by raking without distal movements. Compensatory adjustments in reach length and angle, to maintain end-point accuracy as movements were started from a more lateral position, were less effective using the contralateral limb than ipsilateral limb. With bilateral inactivations, the form of reaching and grasping impairments was identical to that produced by unilateral inactivation, but the magnitude of the reaching impairments was less. We discuss these results in terms of the differential effects of unilateral and bilateral inactivation on corticospinal tract development. We also investigated the degree to which these prehension impairments after unilateral blockade reflect control by each hemisphere. In animals that had received unilateral blockade between postnatal weeks (PWs) 3 and 7, we silenced on-going activity (after PW 11) during task performance using continuous

Differences in the Rate of In Situ Mammary Gland Development and Other Developmental Endpoints in Three Strains of Female Rat Commonly Used in Mammary Carcinogenesis Studies: Implications for Timing of Carcinogen Exposure

PubMed Central

Stanko, Jason P.; Kissling, Grace E.; Chappell, Vesna A.; Fenton, Suzanne E.

2016-01-01

The potential of chemicals to alter susceptibility to mammary tumor formation is often assessed using a carcinogen-induced study design in various rat strains. The rate of mammary gland development must be considered so that the timing of carcinogen administration is impactful. In this study, in situ mammary gland (MG) development was assessed in females of the Harlan Sprague Dawley (Hsd:SD), Charles River Sprague Dawley (Crl:SD), and Charles River Long Evans (Crl:LE) rat strains at postnatal day (PND) 25, 33, and 45. Development was evaluated by physical assessment of growth parameters, developmental scoring, and quantitative morphometric analysis. Though body weight was consistently lower and day of vaginal opening (VO) occurred latest in female Hsd:SD rats, they exhibited accelerated pre-and peripubertal MG development compared to other strains. Glands of Crl:SD and Crl:LE rats exhibited significantly more terminal end buds (TEBs) and TEB/mm than Hsd:SD rats around the time of VO. These data suggest a considerable difference in rate of MG development across commonly used strains, which is independent of body weight and timing of VO. In mammary tumor induction studies employing these strains, administration of the carcinogen should be timed appropriately, based on strain, to specifically target the peak of TEB occurrence. PMID:27613105

Early postnatal exposure to isoflurane causes cognitive deficits and disrupts development of newborn hippocampal neurons via activation of the mTOR pathway

PubMed Central

Lim, Sanghee; Kwak, Minhye; Gray, Christy D.; Xu, Michael; Choi, Jun H.; Junn, Sue; Kim, Jieun; Xu, Jing; Schaefer, Michele; Johns, Roger A.; Song, Hongjun; Ming, Guo-Li; Mintz, C. David

2017-01-01

Clinical and preclinical studies indicate that early postnatal exposure to anesthetics can lead to lasting deficits in learning and other cognitive processes. The mechanism underlying this phenomenon has not been clarified and there is no treatment currently available. Recent evidence suggests that anesthetics might cause persistent deficits in cognitive function by disrupting key events in brain development. The hippocampus, a brain region that is critical for learning and memory, contains a large number of neurons that develop in the early postnatal period, which are thus vulnerable to perturbation by anesthetic exposure. Using an in vivo mouse model we demonstrate abnormal development of dendrite arbors and dendritic spines in newly generated dentate gyrus granule cell neurons of the hippocampus after a clinically relevant isoflurane anesthesia exposure conducted at an early postnatal age. Furthermore, we find that isoflurane causes a sustained increase in activity in the mechanistic target of rapamycin pathway, and that inhibition of this pathway with rapamycin not only reverses the observed changes in neuronal development, but also substantially improves performance on behavioral tasks of spatial learning and memory that are impaired by isoflurane exposure. We conclude that isoflurane disrupts the development of hippocampal neurons generated in the early postnatal period by activating a well-defined neurodevelopmental disease pathway and that this phenotype can be reversed by pharmacologic inhibition. PMID:28683067

Early postnatal exposure to cigarette smoke impairs the antigen-specific T-cell responses in the spleen.

PubMed

Singh, Shashi P; Razani-Boroujerdi, Seddigheh; Pena-Philippides, Juan C; Langley, Raymond J; Mishra, Neerad C; Sopori, Mohan L

2006-12-15

Annually, approximately two million babies are exposed to cigarette smoke in utero and postnatally through cigarette smoking of their mothers. Exposure to mainstream cigarette smoke is known to impair both innate and adaptive immunities, and it has been hypothesized that the effects of in utero exposure to cigarette smoke on children's health might primarily stem from the adverse effects of cigarette smoke on the immune system. To simulate the environment that babies from smoking mothers encounter, we examined the effects of prenatal mainstream and postnatal sidestream cigarette smoke on spleen cell responses. Results show that postnatal exposure of newborn Balb/c mouse pups to sidestream cigarette smoke through the first 6 weeks of life strongly suppresses the antibody response of spleen cells to the T-cell-dependent antigen, sheep red blood cells. The reduction in the antibody response seen within 6 weeks of postnatal smoke exposure is much quicker than the published data on the time 25 weeks) required to establish reproducible immunosuppression in adult rats and mice. Moreover, the immunosuppression is not associated with significant changes in T-cell numbers or subset distribution. While the postnatal exposure to cigarette smoke did not affect the mitogenic response of T and B cells, the exposure inhibited the T cell receptor-mediated rise in the intracellular calcium concentration. These results suggest that the early postnatal period is highly sensitive to the immunosuppressive effects of environmental tobacco smoke, and the effects are causally associated with impaired antigen-mediated signaling in T cells.

The Effects of Prenatal and Early-Postnatal Exposure to Mexico's "Oportunidades" on Long-Term Cognitive Achievement

ERIC Educational Resources Information Center

Sanchez, Alonso

2016-01-01

It is well established that children's early life environments can have significant consequences on their long-term outcomes. Yet, there is still limited empirical evidence on the effects that being exposed during the prenatal and early postnatal periods to positive shocks, such as conditional cash transfers, has on long-term cognitive function.…

FGF-2 signal promotes proliferation of cerebellar progenitor cells and their oligodendrocytic differentiation at early postnatal stage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Naruse, Masae; Shibasaki, Koji; Ishizaki, Yasuki, E-mail: yasukiishizaki@gunma-u.ac.jp

The origins and developmental regulation of cerebellar oligodendrocytes are largely unknown, although some hypotheses of embryonic origins have been suggested. Neural stem cells exist in the white matter of postnatal cerebellum, but it is unclear whether these neural stem cells generate oligodendrocytes at postnatal stages. We previously showed that cerebellar progenitor cells, including neural stem cells, widely express CD44 at around postnatal day 3. In the present study, we showed that CD44-positive cells prepared from the postnatal day 3 cerebellum gave rise to neurospheres, while CD44-negative cells prepared from the same cerebellum did not. These neurospheres differentiated mainly into oligodendrocytesmore » and astrocytes, suggesting that CD44-positive neural stem/progenitor cells might generate oligodendrocytes in postnatal cerebellum. We cultured CD44-positive cells from the postnatal day 3 cerebellum in the presence of signaling molecules known as mitogens or inductive differentiation factors for oligodendrocyte progenitor cells. Of these, only FGF-2 promoted survival and proliferation of CD44-positive cells, and these cells differentiated into O4+ oligodendrocytes. Furthermore, we examined the effect of FGF-2 on cerebellar oligodendrocyte development ex vivo. FGF-2 enhanced proliferation of oligodendrocyte progenitor cells and increased the number of O4+ and CC1+ oligodendrocytes in slice cultures. These results suggest that CD44-positive cells might be a source of cerebellar oligodendrocytes and that FGF-2 plays important roles in their development at an early postnatal stage. - Highlights: • CD44 is expressed in cerebellar neural stem/progenitor cells at postnatal day 3 (P3). • FGF-2 promoted proliferation of CD44-positive progenitor cells from P3 cerebellum. • FGF-2 promoted oligodendrocytic differentiation of CD44-positive progenitor cells. • FGF-2 increased the number of oligodendrocytes in P3 cerebellar slice culture.« less

Screening Tool for Early Postnatal Prediction of Retinopathy of Prematurity in Preterm Newborns (STEP-ROP).

PubMed

Ricard, Caroline A; Dammann, Christiane E L; Dammann, Olaf

2017-01-01

Retinopathy of prematurity (ROP) is a disorder of the preterm newborn characterized by neurovascular disruption in the immature retina that may cause visual impairment and blindness. To develop a clinical screening tool for early postnatal prediction of ROP in preterm newborns based on risk information available within the first 48 h of postnatal life. Using data submitted to the Vermont Oxford Network (VON) between 1995 and 2015, we created logistic regression models based on infants born <28 completed weeks gestational age. We developed a model with 60% of the data and identified birth weight, gestational age, respiratory distress syndrome, non-Hispanic ethnicity, and multiple gestation as predictors of ROP. We tested the model in the remaining 40%, performed tenfold cross-validation, and tested the score in ELGAN study data. Of the 1,052 newborns in the VON database, 627 recorded an ROP status. Forty percent had no ROP, 40% had mild ROP (stages 1 and 2), and 20% had severe ROP (stages 3-5). We created a weighted score to predict any ROP based on the multivariable regression model. A cutoff score of 5 had the best sensitivity (95%, 95% CI 93-97), while maintaining a strong positive predictive value (63%, 95% CI 57-68). When applied to the ELGAN data, sensitivity was lower (72%, 95% CI 69-75), but PPV was higher (80%, 95% CI 77-83). STEP-ROP is a promising screening tool. It is easy to calculate, does not rely on extensive postnatal data collection, and can be calculated early after birth. Early ROP screening may help physicians limit patient exposure to additional risk factors, and may be useful for risk stratification in clinical trials aimed at reducing ROP. © 2017 S. Karger AG, Basel.

Principles of treatment for mammary gland tumors.

PubMed

Novosad, C Andrew

2003-05-01

The mammary glands are frequent locations for the development of tumors. In the dog and cat, early detection and rapid therapy are necessary to prevent both local and distant metastasis. In the dog, this disease can have a range of biologic behaviors, whereas in the cat it is almost always an extremely aggressive disease. Treatment options depend on tumor staging and can include surgery, radiation therapy, chemotherapy, or a combination. As we become better at early diagnosis and are able to implement aggressive therapy, we are becoming more and more successful in the treatment of this disease. In the following article, we will discuss current thoughts surrounding the diagnosis and treatment options for both canine and feline mammary gland tumors.

The influence of early postnatal nutrition on retinopathy of prematurity in extremely low birth weight infants.

PubMed

Porcelli, Peter J; Weaver, R Grey

2010-06-01

Retinopathy of prematurity(ROP) is the most common serious ophthalmic disease in preterm infants. Human milk may provide a protective effect for ROP; however, beneficial effects of human milk preclude randomized trials. Therefore, we conducted a retrospective analysis comparing early postnatal nutrition with ROP development. Evaluate relationship between early postnatal nutriture and ROP surgery. Nutrition data was collected for inborn AGA infants, BW 700-1000 g. ROP surgery was the primary outcome variable. A single pediatric ophthalmologist supervised examinations. All infants received triweekly IM vitamin A as chronic lung disease prophylaxis (Tyson: NEJM, 1999). BW and gestational age were 867+/-85 g and 26.3+/-1.2 weeks (n=77, mean+/-1SD). ROP surgery infants(n=11) received more parenteral nutrition, 1648 mL, and less human milk, 13.8 mL/kg-day, and vitamin E, 1.4 mg/kg-day, during the second postnatal week. Human milk was a negative predictor for ROP surgery, odds ratio=0.94. Both groups met vitamin A recommendations; however, 74% was administered via IM injections. Neither group met vitamin E recommendations. Human milk feeding, parenteral nutrition volume and vitamin E intake were predictors for ROP surgery. IM vitamin A injections provided the majority of vitamin A; vitamin E administration was insufficient. Improving human milk feeding rates and vitamin dosing options may affect ROP surgery rates. Copyright 2010 Elsevier Ltd. All rights reserved.

Early postnatal GFAP-expressing cells produce multilineage progeny in cerebrum and astrocytes in cerebellum of adult mice.

PubMed

Guo, Zhibao; Wang, Xijuan; Xiao, Jun; Wang, Yihui; Lu, Hong; Teng, Junfang; Wang, Wei

2013-09-26

Early postnatal GFAP-expressing cells are thought to be immature astrocytes. However, it is not clear if they possess multilineage capacity and if they can generate different lineages (astrocytes, neurons and oligodendrocytes) in the brain of adult mice. In order to identify the fate of astroglial cells in the postnatal brain, hGFAP-Cre-ER(T2) transgenic mice were crossed with the R26R Cre reporter mouse strains which exhibit constitutive expression of β-galactosidase (β-gal). Mice carrying the hGFAP-Cre-ER(T2)/R26R transgene were treated with Tamoxifen to induce Cre recombination in astroglial cells at postnatal (P) day 6 and Cre recombinase-expressing cells were identified by X-gal staining. Immunohistochemical staining was used to identify the type(s) of these reporter-tagged cells. Sixty days after recombination, X-gal-positive cells in different cerebral regions of the adult mice expressed the astroglial markers Blbp and GFAP, the neuronal marker NeuN, the oligodendrocyte precursor cell marker NG2 and the mature oligodendrocyte marker CC1. X-gal-positive cells in the cerebellum coexpressed the astroglial marker Blbp, but not the granule cell marker NeuN, Purkinje cell marker Calbindin or oligodendrocyte precursor cell marker NG2. Our genetic fate mapping data demonstrated that early postnatal GFAP-positive cells possessed multilineage potential and eventually differentiated into neurons, astrocytes, and oligodendrocyte precursor cells in the cerebrum and into astrocytes (including Bergmann glia) in the cerebellum of adult mice. © 2013 Elsevier B.V. All rights reserved.

Postnatal penile growth concurrent with mini-puberty predicts later sex-typed play behavior: Evidence for neurobehavioral effects of the postnatal androgen surge in typically developing boys.

PubMed

Pasterski, Vickie; Acerini, Carlo L; Dunger, David B; Ong, Ken K; Hughes, Ieuan A; Thankamony, Ajay; Hines, Melissa

2015-03-01

The masculinizing effects of prenatal androgens on human neurobehavioral development are well established. Also, the early postnatal surge of androgens in male infants, or mini-puberty, has been well documented and is known to influence physiological development, including penile growth. However, neurobehavioral effects of androgen exposure during mini-puberty are largely unknown. The main aim of the current study was to evaluate possible neurobehavioral consequences of mini-puberty by relating penile growth in the early postnatal period to subsequent behavior. Using multiple linear regression, we demonstrated that penile growth between birth and three months postnatal, concurrent with mini-puberty, significantly predicted increased masculine/decreased feminine behavior assessed using the Pre-school Activities Inventory (PSAI) in 81 healthy boys at 3 to 4years of age. When we controlled for other potential influences on masculine/feminine behavior and/or penile growth, including variance in androgen exposure prenatally and body growth postnally, the predictive value of penile growth in the early postnatal period persisted. More specifically, prenatal androgen exposure, reflected in the measurement of anogenital distance (AGD), and early postnatal androgen exposure, reflected in penile growth from birth to 3months, were significant predictors of increased masculine/decreased feminine behavior, with each accounting for unique variance. Our findings suggest that independent associations of PSAI with AGD at birth and with penile growth during mini-puberty reflect prenatal and early postnatal androgen exposures respectively. Thus, we provide a novel and readily available approach for assessing effects of early androgen exposures, as well as novel evidence that early postnatal aes human neurobehavioral development. Copyright © 2015. Published by Elsevier Inc.

Diversification of intrinsic motoneuron electrical properties during normal development and botulinum toxin-induced muscle paralysis in early postnatal mice.

PubMed

Nakanishi, S T; Whelan, P J

2010-05-01

During early postnatal development, between birth and postnatal days 8-11, mice start to achieve weight-bearing locomotion. In association with the progression of weight-bearing locomotion there are presumed developmental changes in the intrinsic electrical properties of spinal -motoneurons. However, these developmental changes in the properties of -motoneuron properties have not been systematically explored in mice. Here, data are presented documenting the developmental changes of selected intrinsic motoneuron electrical properties, including statistically significant changes in action potential half-width, intrinsic excitability and diversity (quantified as coefficient of variation) of rheobase current, afterhyperpolarization half-decay time, and input resistance. In various adult mammalian preparations, the maintenance of intrinsic motoneuron electrical properties is dependent on activity and/or transmission-sensitive motoneuron-muscle interactions. In this study, we show that botulinum toxin-induced muscle paralysis led to statistically significant changes in the normal development of intrinsic motoneuron electrical properties in the postnatal mouse. This suggests that muscle activity during early neonatal life contributes to the development of normal motoneuron electrical properties.

Post-natal myogenic and adipogenic developmental

PubMed Central

Konings, Gonda; van Weeghel, Michel; van den Hoogenhof, Maarten MG; Gijbels, Marion; van Erk, Arie; Schoonderwoerd, Kees; van den Bosch, Bianca; Dahlmans, Vivian; Calis, Chantal; Houten, Sander M; Misteli, Tom

2011-01-01

A-type lamins are a major component of the nuclear lamina. Mutations in the LMNA gene, which encodes the A-type lamins A and C, cause a set of phenotypically diverse diseases collectively called laminopathies. While adult LMNA null mice show various symptoms typically associated with laminopathies, the effect of loss of lamin A/C on early post-natal development is poorly understood. Here we developed a novel LMNA null mouse (LMNAGT−/−) based on genetrap technology and analyzed its early post-natal development. We detect LMNA transcripts in heart, the outflow tract, dorsal aorta, liver and somites during early embryonic development. Loss of A-type lamins results in severe growth retardation and developmental defects of the heart, including impaired myocyte hypertrophy, skeletal muscle hypotrophy, decreased amounts of subcutaneous adipose tissue and impaired ex vivo adipogenic differentiation. These defects cause death at 2 to 3 weeks post partum associated with muscle weakness and metabolic complications, but without the occurrence of dilated cardiomyopathy or an obvious progeroid phenotype. Our results indicate that defective early post-natal development critically contributes to the disease phenotypes in adult laminopathies. PMID:21818413

Early postnatal hyperglycaemia is a risk factor for treatment-demanding retinopathy of prematurity.

PubMed

Slidsborg, Carina; Jensen, Louise Bering; Rasmussen, Steen Christian; Fledelius, Hans Callø; Greisen, Gorm; Cour, Morten de la

2018-01-01

To investigate whether neonatal hyperglycaemia in the first postnatal week is associated with treatment-demanding retinopathy of prematurity (ROP). This is a Danish national, retrospective, case-control study of premature infants (birth period 2003-2006). Three national registers were searched, and data were linked through a unique civil registration number. The study sample consisted of 106 cases each matched with two comparison infants. Matching criteria were gestational age (GA) at birth, ROP not registered and born at the same neonatal intensive care unit. Potential 'new' risk factors were analysed in a multivariate logistic regression model, while adjusted for previously recognised risk factors (ie, GA at birth, small for gestational age, multiple birth and male sex). Hospital records of 310 preterm infants (106 treated; 204 comparison infants) were available. Nutrition in terms of energy (kcal/kg/week) and protein (g/kg/week) given to the preterm infants during the first postnatal week were statistically insignificant between the study groups (Mann-Whitney U test; p=0.165/p=0.163). Early postnatal weight gain between the two study groups was borderline significant (t-test; p=0.047). Hyperglycaemic events (indexed value) were statistically significantly different between the two study groups (Mann-Whitney U test; p<0.001). Hyperglycaemia was a statistically independent risk factor (OR: 1.022; 95% CI 1.002 to 1.042; p=0.031). An independent association was found between the occurrence of hyperglycaemic events during the first postnatal week and later development of treatment-demanding ROP, when adjusted for known risk factors. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Type I intrinsically photosensitive retinal ganglion cells of early post-natal development correspond to the M4 subtype.

PubMed

Sexton, Timothy J; Bleckert, Adam; Turner, Maxwell H; Van Gelder, Russell N

2015-06-21

Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate circadian light entrainment and the pupillary light response in adult mice. In early development these cells mediate different processes, including negative phototaxis and the timing of retinal vascular development. To determine if ipRGC physiologic properties also change with development, we measured ipRGC cell density and light responses in wild-type mouse retinas at post-natal days 8, 15 and 30. Melanopsin-positive cell density decreases by 17% between post-natal days 8 and 15 and by 25% between days 8 and 30. This decrease is due specifically to a decrease in cells co-labeled with a SMI-32, a marker for alpha-on ganglion cells (corresponding to adult morphologic type M4 ipRGCs). On multi-electrode array recordings, post-natal day 8 (P8) ipRGC light responses show more robust firing, reduced adaptation and more rapid recovery from short and extended light pulses than do the light responses of P15 and P30 ipRGCs. Three ipRGC subtypes - Types I-III - have been defined in early development based on sensitivity and latency on multielectrode array recordings. We find that Type I cells largely account for the unique physiologic properties of P8 ipRGCs. Type I cells have previously been shown to have relatively short latencies and high sensitivity. We now show that Type I cells show have rapid and robust recovery from long and short bright light exposures compared with Type II and III cells, suggesting differential light adaptation mechanisms between cell types. By P15, Type I ipRGCs are no longer detectable. Loose patch recordings of P8 M4 ipRGCs demonstrate Type I physiology. Type I ipRGCs are found only in early development. In addition to their previously described high sensitivity and rapid kinetics, these cells are uniquely resistant to adaptation and recover quickly and fully to short and prolonged light exposure. Type I ipRGCs correspond to the SMI-32 positive, M4 subtype and largely lose

Early post-natal neuroactive steroid manipulation modulates ondansetron effects on initial periods of alcohol consumption in rats.

PubMed

Bartolomé, Iris; Llidó, Anna; Darbra, Sònia; Pallarès, Marc

2018-06-21

Neuroactive steroids (NS) such as allopregnanolone are crucial for brain development and adult behaviour. Early post-natal alterations of NS by administering finasteride induce a decrease in the sensitivity to stimulant effects of low alcohol doses, an increase in alcohol consumption, and a decrease in ventrostriatal dopamine and serotonin levels. The aim of the present study is to observe if the effects of the 5HT3 receptor antagonist ondansetron on initial alcohol consumption are modulated by post-natal NS manipulation. For this purpose, allopregnanolone, finasteride, or vehicle was injected from day 5 to 9. In adulthood, a novel object preference test was carried out in order to detect a possible novelty-seeking pattern in our animals, which has been related to vulnerability to drug abuse. The subjects then had access to two bottles (alcohol or control solutions) one hour daily for two consecutive weeks. Ondansetron (0.01 mg/kg, 0.1 mg/kg or vehicle) was administered before the hour of consumption in the initial phase (days 1, 2, 3) of the procedure, and after prolonged alcohol intake (days 11, 12, 13). Results indicated that finasteride animals showed a higher preference to explore the new object, as well as a higher alcohol consumption than the rest of the groups. Moreover, 0.1 mg/kg of ondansetron decreased alcohol consumption, but only in the post-natal finasteride group, suggesting a possible increase in 5HT3 receptor sensitivity in these animals. In conclusion, NS manipulation in crucial stages of development, such as early post-natal periods, seems to play an important role on the effects of ondansetron on alcohol intake and in the vulnerability to develop drug use or abuse. Copyright © 2018. Published by Elsevier Inc.

Prenatal and Early Postnatal Odorant Exposure Heightens Odor-Evoked Mitral Cell Responses in the Mouse Olfactory Bulb

PubMed Central

2017-01-01

Abstract Early sensory experience shapes the anatomy and function of sensory circuits. In the mouse olfactory bulb (OB), prenatal and early postnatal odorant exposure through odorized food (food/odorant pairing) not only increases the volume of activated glomeruli but also increases the number of mitral and tufted cells (M/TCs) connected to activated glomeruli. Given the importance of M/TCs in OB output and in mediating lateral inhibitory networks, increasing the number of M/TCs connected to a single glomerulus may significantly change odorant representation by increasing the total output of that glomerulus and/or by increasing the strength of lateral inhibition mediated by cells connected to the affected glomerulus. Here, we seek to understand the functional impact of this long-term odorant exposure paradigm on the population activity of mitral cells (MCs). We use viral expression of GCaMP6s to examine odor-evoked responses of MCs following prenatal and early postnatal odorant exposure to two dissimilar odorants, methyl salicylate (MS) and hexanal, which are both strong activators of glomeruli on the dorsal OB surface. Previous work suggests that odor familiarity may decrease odor-evoked MC response in rodents. However, we find that early food-based odorant exposure significantly changes MC responses in an unexpected way, resulting in broad increases in the amplitude, number, and reliability of excitatory MC responses across the dorsal OB. PMID:28955723

Sequestration of human cytomegalovirus by human renal and mammary epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Twite, Nicolas; Andrei, Graciela; Kummert, Caroline

2014-07-15

Urine and breast milk represent the main routes of human cytomegalovirus (HCMV) transmission but the contribution of renal and mammary epithelial cells to viral excretion remains unclear. We observed that kidney and mammary epithelial cells were permissive to HCMV infection and expressed immediate early, early and late antigens within 72 h of infection. During the first 24 h after infection, high titers of infectious virus were measured associated to the cells and in culture supernatants, independently of de novo synthesis of virus progeny. This phenomenon was not observed in HCMV-infected fibroblasts and suggested the sequestration and the release of HCMVmore » by epithelial cells. This hypothesis was supported by confocal and electron microscopy analyses. The sequestration and progressive release of HCMV by kidney and mammary epithelial cells may play an important role in the excretion of the virus in urine and breast milk and may thereby contribute to HCMV transmission. - Highlights: • Primary renal and mammary epithelial cells are permissive to HCMV infection. • HCMV is sequestered by epithelial cells and this phenomenon does not require viral replication. • HCMV sequestration by epithelial cells is reduced by antibodies and IFN-γ.« less

Mammary Adipose Tissue-derived Lysophospholipids Promote Estrogen Receptor-negative Mammary Epithelial Cell Proliferation

PubMed Central

Volden, Paul A.; Skor, Maxwell N.; Johnson, Marianna B.; Singh, Puneet; Patel, Feenalie N.; McClintock, Martha K.; Brady, Matthew J.; Conzen, Suzanne D.

2016-01-01

Lysophosphatidic acid (LPA), acting in an autocrine or paracrine fashion through G protein-coupled receptors, has been implicated in many physiological and pathological processes including cancer. LPA is converted to lysophosphatidylcholine (LPC) by the secreted phospholipase, autotaxin (ATX). Although various cell types can produce ATX, adipocyte-derived ATX is believed to be the major source of circulating ATX and also to be the major regulator of plasma LPA. In addition to ATX, adipocytes secrete numerous other factors (adipokines); although several adipokines have been implicated in breast cancer biology, the contribution of mammary adipose tissue-derived LPC/ATX/LPA (LPA-axis) signaling to breast cancer is poorly understood. Using mammary fat-conditioned medium, we investigated the contribution of LPA signaling to mammary epithelial cancer cell biology and identified LPA signaling as a significant contributor to the oncogenic effects of the mammary adipose tissue secretome. To interrogate the role of mammary fat in the LPA-axis during breast cancer progression, we exposed mammary adipose tissue to secreted factors from estrogen receptor-negative mammary epithelial cell lines and monitored changes in the mammary fat pad LPA-axis. Our data indicate that bidirectional interactions between mammary cancer cells and mammary adipocytes alter the local LPA-axis and increase ATX expression in the mammary fat pad during breast cancer progression. Thus, the LPC/ATX/LPA axis may be a useful target for prevention in patients at risk of ER-negative breast cancer. PMID:26862086

Mammary ductal growth is impaired in mice lacking leptin-dependent signal transducer and activator of transcription 3 signaling.

PubMed

Thorn, Stephanie R; Giesy, Sarah L; Myers, Martin G; Boisclair, Yves R

2010-08-01

Mice lacking leptin (ob/ob) or its full-length receptor (db/db) are obese and reproductively incompetent. Fertility, pregnancy, and lactation are restored, respectively, in ob/ob mice treated with leptin through mating, d 6.5 post coitum, and pregnancy. Therefore, leptin signaling is needed for lactation, but the timing of its action and the affected mammary process remain unknown. To address this issue, we used s/s mice lacking only leptin-dependent signal transducer and activator of transcription (STAT)3 signaling. These mice share many features with db/db mice, including obesity, but differ by retaining sufficient activity of the hypothalamic-pituitary-ovarian axis to support reproduction. The s/s mammary epithelium was normal at 3 wk of age but failed to expand through the mammary fat pad (MFP) during the subsequent pubertal period. Ductal growth failure was not corrected by estrogen therapy and did not relate to inadequate IGF-I production by the MFP or to the need for epithelial or stromal leptin-STAT3 signaling. Ductal growth failure coincided with adipocyte hypertrophy and increased MFP production of leptin, TNFalpha, and IL6. These cytokines, however, were unable to inhibit the proliferation of a collection of mouse mammary epithelial cell lines. In conclusion, the very first step of postnatal mammary development fails in s/s mice despite sufficient estrogen IGF-I and an hypothalamic-pituitary-ovarian axis capable of supporting reproduction. This failure is not caused by mammary loss of leptin-dependent STAT3 signaling or by the development of inflammation. These data imply the existence of an unknown mechanism whereby leptin-dependent STAT3 signaling and obesity alter mammary ductal development.

Developmental Injury to the Cerebellar Cortex Following Hydroxyurea Treatment in Early Postnatal Life: An Immunohistochemical and Electron Microscopic Study.

PubMed

Martí, Joaquín; Molina, Vanesa; Santa-Cruz, M C; Hervás, José P

2017-02-01

Postnatal development of the cerebellar cortex was studied in rats administered with a single dose (2 mg/g) of the cytotoxic agent hydroxyurea (HU) on postnatal day (P) 9 and collected at appropriate times ranging from 6 h to 45 days. Quantification of several parameters such as the density of pyknotic, mitotic, BrdU-positive, and vimentin-stained cells revealed that HU compromises the survival of the external granular layer (EGL) cells. Moreover, vimentin immunocytochemistry revealed overexpression and thicker immunoreactive glial processes in HU-treated rats. On the other hand, we also show that HU leads to the activation of apoptotic cellular events, resulting in a substantial number of dying EGL cells, as revealed by TUNEL staining and at the electron microscope level. Additionally, we quantified several features of the cerebellar cortex of rats exposed to HU in early postnatal life and collected in adulthood. Data analysis indicated that the analyzed parameters were less pronounced in rats administered with this agent. Moreover, we observed several alterations in the cerebellar cortex cytoarchitecture of rats injected with HU. Anomalies included ectopic placement of Purkinje cells and abnormities in the dendritic arbor of these macroneurons. Ectopic granule cells were also found in the molecular layer. These findings provide a clue for investigating the mechanisms of HU-induced toxicity during the development of the central nervous system. Our results also suggest that it is essential to avoid underestimating the adverse effects of this hydroxylated analog of urea when administered during early postnatal life.

Effect of early postnatal exposure to valproate on neurobehavioral development and regional BDNF expression in two strains of mice.

PubMed

Bath, Kevin G; Pimentel, Tiare

2017-05-01

Valproate has been used for over 30years as a first-line treatment for epilepsy. In recent years, prenatal exposure to valproate has been associated with teratogenic effects, limiting its use in women that are pregnant or of childbearing age. However, despite its potential detrimental effects on development, valproate continues to be prescribed at high rates in pediatric populations in some countries. Animal models allow us to test hypotheses regarding the potential effects of postnatal valproate exposure on neurobehavioral development, as well as identify potential mechanisms mediating observed effects. Here, we tested the effect of early postnatal (P4-P11) valproate exposure (100mg/kg and 200mg/kg) on motor and affective development in two strains of mice, SVE129 and C57Bl/6N. We also assessed the effect of early valproate exposure on regional BDNF protein levels, a potential target of valproate, and mediator of neurodevelopmental outcomes. We found that early life valproate exposure led to significant motor impairments in both SVE129 and C57Bl/6N mice. Both lines of mice showed significant delays in weight gain, as well as impairments in the righting reflex (P7-8), wire hang (P17), open field (P12 and P21), and rotarod (P25 and P45) tasks. Interestingly, some of the early locomotor effects were strain- and dose-dependent. We observed no effects of valproate on early markers of anxiety-like behavior. Importantly, early life valproate exposure had significant effects on regional BDNF expression, leading to a near 50% decrease in BDNF levels in the cerebellum of both strains of mice, while not impacting hippocampal BDNF protein levels. These observations indicate that postnatal exposure to valproate may have significant, and region-specific effects, on neural and behavioral development, with specific consequences for cerebellar development and motor function. Copyright © 2017 Elsevier Inc. All rights reserved.

A Novel Mammary Fat Pad Transplantation Technique to Visualize the Vessel Generation of Vascular Endothelial Stem Cells.

PubMed

Yu, Qing Cissy; Song, Wenqian; Lai, Dengwen; Zeng, Yi Arial

2017-08-03

Endothelial cells (ECs) are the fundamental building blocks of the vascular architecture and mediate vascular growth and remodeling to ensure proper vessel development and homeostasis. However, studies on endothelial lineage hierarchy remain elusive due to the lack of tools to gain access as well as to directly evaluate their behavior in vivo. To address this shortcoming, a new tissue model to study angiogenesis using the mammary fat pad has been developed. The mammary gland develops mostly in the postnatal stages, including puberty and pregnancy, during which robust epithelium proliferation is accompanied by extensive vascular remodeling. Mammary fat pads provide space, matrix, and rich angiogenic stimuli from the growing mammary epithelium. Furthermore, mammary fat pads are located outside the peritoneal cavity, making them an easily accessible grafting site for assessing the angiogenic potential of exogenous cells. This work also describes an efficient tracing approach using fluorescent reporter mice to specifically label the targeted population of vascular endothelial stem cells (VESCs) in vivo. This lineage tracing method, coupled with subsequent tissue whole-mount microscopy, enable the direct visualization of targeted cells and their descendants, through which the proliferation capability can be quantified and the differentiation commitment can be fate-mapped. Using these methods, a population of bipotent protein C receptor (Procr) expressing VESCs has recently been identified in multiple vascular systems. Procr + VESCs, giving rise to both new ECs and pericytes, actively contribute to angiogenesis during development, homeostasis, and injury repair. Overall, this manuscript describes a new mammary fat pad transplantation and in vivo lineage tracing techniques that can be used to evaluate the stem cell properties of VESCs.

In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland.

PubMed

El Sheikh Saad, H; Toullec, A; Vacher, S; Pocard, M; Bieche, I; Perrot-Applanat, M

2013-02-01

Exposure to low doses of environmental estrogens such as bisphenol A and genistein (G) alters mammary gland development. The effects of environmental anti-androgens, such as the fungicide vinclozolin (V), on mammary gland morphogenesis are unknown. We previously reported that perinatal exposure to G, V, and the GV combination causes histological changes in the mammary gland during the peripubertal period, suggesting alterations to the peripubertal hormone response. We now investigate whether perinatal exposure to these compounds alters the gene expression profiles of the developing glands to identify the dysregulated signaling pathways and the underlying mechanisms. G, V, or GV (1 mg/kg body weight per day) was added to diet of Wistar rats, from conception to weaning; female offspring mammary glands were collected at postnatal days (PNDs) 35 and 50. Genes displaying differential expression and belonging to different functional categories were validated by quantitative PCR and immunocytochemistry. At PND35, G had little effect; the slight changes noted were in genes related to morphogenesis. The changes following exposure to V concerned the functional categories associated with development (Cldn1, Krt17, and Sprr1a), carbohydrate metabolism, and steroidogenesis. The GV mixture upregulated genes (Krt17, Pvalb, and Tnni2) involved in muscle development, indicating effects on myoepithelial cells during mammary gland morphogenesis. Importantly, at PND50, cycling females exposed to GV showed an increase in the expression of genes (Csn2, Wap, and Elf5) related to differentiation, consistent with the previously reported abnormal lobuloalveolar development previously described. Thus, perinatal exposure to GV alters the mammary gland hormone response differently at PND35 (puberty) and in animals with established cycles.

Varying Susceptibility of the Female Mammary Gland to In Utero Windows of BPA Exposure.

PubMed

Hindman, Andrea R; Mo, Xiaokui Molly; Helber, Hannah L; Kovalchin, Claire E; Ravichandran, Nanditha; Murphy, Alina R; Fagan, Abigail M; St John, Pamela M; Burd, Craig J

2017-10-01

In utero exposure to the endocrine disrupting compound bisphenol A (BPA) is known to disrupt mammary gland development and increase tumor susceptibility in rodents. It is unclear whether different periods of in utero development might be more susceptible to BPA exposure. We exposed pregnant CD-1 mice to BPA at different times during gestation that correspond to specific milestones of in utero mammary gland development. The mammary glands of early-life and adult female mice, exposed in utero to BPA, were morphologically and molecularly (estrogen receptor-α and Ki67) evaluated for developmental abnormalities. We found that BPA treatment occurring before mammary bud invasion into the mesenchyme [embryonic day (E)12.5] incompletely resulted in the measured phenotypes of mammary gland defects. Exposing mice up to the point at which the epithelium extends into the precursor fat pad (E16.5) resulted in a nearly complete BPA phenotype and exposure during epithelial extension (E15.5 to E18.5) resulted in a partial phenotype. Furthermore, the relative differences in phenotypes between exposure windows highlight the substantial correlations between early-life molecular changes (estrogen receptor-α and Ki67) in the stroma and the epithelial elongation defects in mammary development. These data further implicate BPA action in the stroma as a critical mediator of epithelial phenotypes. Copyright © 2017 Endocrine Society.

Selection of early-occurring mutations dictates hormone-independent progression in mouse mammary tumor lines.

PubMed

Gattelli, Albana; Zimberlin, María N; Meiss, Roberto P; Castilla, Lucio H; Kordon, Edith C

2006-11-01

Mice harboring three mouse mammary tumor virus (MMTV) variants develop pregnancy-dependent (PD) tumors that progress to pregnancy-independent (PI) behavior through successive passages. Herein, we identified 10 predominant insertions in PI transplants from 8 independent tumor lines. These mutations were also detected in small cell populations in the early PD passages. In addition, we identified a new viral insertion upstream of the gene Rspo3, which is overexpressed in three of the eight independent tumor lines and codes for a protein very similar to the recently described protein encoded by Int7. This study suggests that during progression towards hormone independence, clonal expansion of cells with specific mutations might be more relevant than the occurrence of new MMTV insertions.

Selection of Early-Occurring Mutations Dictates Hormone-Independent Progression in Mouse Mammary Tumor Lines▿

PubMed Central

Gattelli, Albana; Zimberlin, María N.; Meiss, Roberto P.; Castilla, Lucio H.; Kordon, Edith C.

2006-01-01

Mice harboring three mouse mammary tumor virus (MMTV) variants develop pregnancy-dependent (PD) tumors that progress to pregnancy-independent (PI) behavior through successive passages. Herein, we identified 10 predominant insertions in PI transplants from 8 independent tumor lines. These mutations were also detected in small cell populations in the early PD passages. In addition, we identified a new viral insertion upstream of the gene Rspo3, which is overexpressed in three of the eight independent tumor lines and codes for a protein very similar to the recently described protein encoded by Int7. This study suggests that during progression towards hormone independence, clonal expansion of cells with specific mutations might be more relevant than the occurrence of new MMTV insertions. PMID:16971449

Growth Hormone and Insulin-Like Growth Factor-I in the Transition from Normal Mammary Development to Preneoplastic Mammary Lesions

PubMed Central

Kleinberg, David L.; Wood, Teresa L.; Furth, Priscilla A.; Lee, Adrian V.

2009-01-01

Adult female mammary development starts at puberty and is controlled by tightly regulated cross-talk between a group of hormones and growth factors. Although estrogen is the initial driving force and is joined by luteal phase progesterone, both of these hormones require GH-induced IGF-I in the mammary gland in order to act. The same group of hormones, when experimentally perturbed, can lead to development of hyperplastic lesions and increase the chances, or be precursors, of mammary carcinoma. For example, systemic administration of GH or IGF-I causes mammary hyperplasia, and overproduction of IGF-I in transgenic animals can cause the development of usual or atypical hyperplasias and sometimes carcinoma. Although studies have clearly demonstrated the transforming potential of both GH and IGF-I receptor in cell culture and in animals, debate remains as to whether their main role is actually instructive or permissive in progression to cancer in vivo. Genetic imprinting has been shown to occur in precursor lesions as early as atypical hyperplasia in women. Thus, the concept of progression from normal development to cancer through precursor lesions sensitive to hormones and growth factors discussed above is gaining support in humans as well as in animal models. Indeed, elevation of estrogen receptor, GH, IGF-I, and IGF-I receptor during progression suggests a role for these pathways in this process. New agents targeting the GH/IGF-I axis may provide a novel means to block formation and progression of precursor lesions to overt carcinoma. A novel somatostatin analog has recently been shown to prevent mammary development in rats via targeted IGF-I action inhibition at the mammary gland. Similarly, pegvisomant, a GH antagonist, and other IGF-I antagonists such as IGF binding proteins 1 and 5 also block mammary gland development. It is, therefore, possible that inhibition of IGF-I action, or perhaps GH, in the mammary gland may eventually play a role in breast cancer

Assessing Susceptibility from Early-Life Exposure to Carcinogens

PubMed Central

Barton, Hugh A.; Cogliano, V. James; Flowers, Lynn; Valcovic, Larry; Setzer, R. Woodrow; Woodruff, Tracey J.

2005-01-01

Cancer risk assessment methods currently assume that children and adults are equally susceptible to exposure to chemicals. We reviewed available scientific literature to determine whether this was scientifically supported. We identified more than 50 chemicals causing cancer after perinatal exposure. Human data are extremely limited, with radiation exposures showing increased early susceptibility at some tumor sites. Twenty-seven rodent studies for 18 chemicals had sufficient data after postnatal and adult exposures to quantitatively estimate potential increased susceptibility from early-life exposure, calculated as the ratio of juvenile to adult cancer potencies for three study types: acute dosing, repeated dosing, and lifetime dosing. Twelve of the chemicals act through a mutagenic mode of action. For these, the geometric mean ratio was 11 for lifetime exposures and 8.7 for repeat exposures, with a ratio of 10 for these studies combined. The geometric mean ratio for acute studies is 1.5, which was influenced by tissue-specific results [geometric mean ratios for kidney, leukemia, liver, lymph, mammary, nerve, reticular tissue, thymic lymphoma, and uterus/vagina > 1 (range, 1.6–8.1); forestomach, harderian gland, ovaries, and thyroid < 1 (range, 0.033–0.45)]. Chemicals causing cancer through other modes of action indicate some increased susceptibility from postnatal exposure (geometric mean ratio is 3.4 for lifetime exposure, 2.2 for repeat exposure). Early exposures to compounds with endocrine activity sometimes produce different tumors after exposures at different ages. These analyses suggest increased susceptibility to cancer from early-life exposure, particularly for chemicals acting through a mutagenic mode of action. PMID:16140616

Glial glycine transporter 1 function is essential for early postnatal survival but dispensable in adult mice.

PubMed

Eulenburg, Volker; Retiounskaia, Marina; Papadopoulos, Theofilos; Gomeza, Jesús; Betz, Heinrich

2010-07-01

The glycine transporter 1 (GlyT1) is expressed in astrocytes and selected neurons of the mammalian CNS. In newborn mice, GlyT1 is crucial for efficient termination of glycine-mediated inhibitory neurotransmission. Furthermore, GlyT1 has been implicated in the regulation of excitatory N-methyl-D-asparate (NMDA) receptors. To evaluate whether glial and neuronal GlyT1 have distinct roles at inhibitory synapses, we inactivated the GlyT1 gene cell type-specifically using mice carrying floxed GlyT1 alleles GlyT1((+)/+)). GlyT1((+)/(+)) mice expressing Cre recombinase in glial cells developed severe neuromotor deficits during the first postnatal week, which mimicked the phenotype of conventional GlyT1 knock-out mice and are consistent with glycinergic over-inhibition. In contrast, Cre-mediated inactivation of the GlyT1 gene in neuronal cells did not result in detectable motor impairment. Notably, some animals deficient for glial GlyT1 survived the first postnatal week and did not develop neuromotor deficits throughout adulthood, although GlyT1 expression was efficiently reduced. Thus, glial GlyT1 is critical for the regulation of glycine levels at inhibitory synapses only during early postnatal life. Copyright 2010 Wiley-Liss, Inc.

Prenatal Exposure to BPA Alters the Epigenome of the Rat Mammary Gland and Increases the Propensity to Neoplastic Development

PubMed Central

Dhimolea, Eugen; Wadia, Perinaaz R.; Murray, Tessa J.; Settles, Matthew L.; Treitman, Jo D.; Sonnenschein, Carlos; Shioda, Toshi; Soto, Ana M.

2014-01-01

Exposure to environmental estrogens (xenoestrogens) may play a causal role in the increased breast cancer incidence which has been observed in Europe and the US over the last 50 years. The xenoestrogen bisphenol A (BPA) leaches from plastic food/beverage containers and dental materials. Fetal exposure to BPA induces preneoplastic and neoplastic lesions in the adult rat mammary gland. Previous results suggest that BPA acts through the estrogen receptors which are detected exclusively in the mesenchyme during the exposure period by directly altering gene expression, leading to alterations of the reciprocal interactions between mesenchyme and epithelium. This initiates a long sequence of altered morphogenetic events leading to neoplastic transformation. Additionally, BPA induces epigenetic changes in some tissues. To explore this mechanism in the mammary gland, Wistar-Furth rats were exposed subcutaneously via osmotic pumps to vehicle or 250 µg BPA/kg BW/day, a dose that induced ductal carcinomas in situ. Females exposed from gestational day 9 to postnatal day (PND) 1 were sacrificed at PND4, PND21 and at first estrus after PND50. Genomic DNA (gDNA) was isolated from the mammary tissue and immuno-precipitated using anti-5-methylcytosine antibodies. Detection and quantification of gDNA methylation status using the Nimblegen ChIP array revealed 7412 differentially methylated gDNA segments (out of 58207 segments), with the majority of changes occurring at PND21. Transcriptomal analysis revealed that the majority of gene expression differences between BPA- and vehicle-treated animals were observed later (PND50). BPA exposure resulted in higher levels of pro-activation histone H3K4 trimethylation at the transcriptional initiation site of the alpha-lactalbumin gene at PND4, concomitantly enhancing mRNA expression of this gene. These results show that fetal BPA exposure triggers changes in the postnatal and adult mammary gland epigenome and alters gene expression patterns

Analysis of Milk from Mothers Who Delivered Prematurely Reveals Few Changes in Proteases and Protease Inhibitors across Gestational Age at Birth and Infant Postnatal Age.

PubMed

Demers-Mathieu, Veronique; Nielsen, Søren Drud; Underwood, Mark A; Borghese, Robyn; Dallas, David C

2017-06-01

Background: Peptidomics research has demonstrated that protease activity is higher in breast milk from preterm-delivering mothers than from term-delivering mothers. However, to our knowledge, the effect of the degree of prematurity and postnatal age on proteases and protease inhibitors in human milk remains unknown. Objective: We aimed to determine the change of proteases and protease inhibitors in milk from mothers who delivered prematurely across gestational age (GA) and postnatal age. Methods: Milk samples were collected from 18 mothers aged 26-40 y who delivered preterm infants and who lacked mastitis. For analysis, samples were separated into 2 groups: 9 from early GA (EGA) (24-26 wk GA)-delivering mothers and 9 from late GA (LGA) (27-32 wk GA)-delivering mothers. Within the 9 samples in each group, the collection time ranged from postnatal days 2 to 47. The activity and predicted activity of proteases in preterm milk were determined with the use of fluorometric and spectrophotometric assays and peptidomics, respectively. Protease and protease inhibitor concentrations were determined with the use of ELISA. Linear mixed models were applied to compare enzymes across GA and postnatal age. Results: Carboxypeptidase B2, kallikrein, plasmin, elastase, thrombin, and cytosol aminopeptidase were present and active in the milk of preterm-delivering mothers. Most milk protease and antiprotease concentrations did not change with GA or postnatal age. However, the concentration and activity of kallikrein, the most abundant and active protease in preterm milk, increased by 25.4 ng · mL -1 · d -1 and 0.454 μg · mL -1 · d -1 postnatally, respectively, in EGA milk samples while remaining stable in LGA milk samples. Conclusions: This research demonstrates that proteases are active in human milk and begin to degrade milk protein within the mammary gland before consumption by infants. Proteases and protease inhibitors in milk from mothers of premature infants mostly did not

Telomere length dynamics differ in foetal and early post-natal human leukocytes in a longitudinal study.

PubMed

Holmes, Denise K; Bellantuono, Ilaria; Walkinshaw, Steve A; Alfirevic, Zarko; Johnston, Tracey A; Subhedar, Nimish V; Chittick, Rachel; Swindell, Richard; Wynn, Robert F

2009-06-01

Haemopoietic stem cells (HSC) undergo a process of self renewal to constantly maintain blood cell turnover. However, it has become apparent that adult HSC lose their self-renewal ability with age. Telomere shortening in peripheral blood leukocytes has been seen to occur with age and it has been associated with loss of HSC proliferative capacity and cellular ageing. In contrast foetal HSC are known to have greater proliferative capacity than post-natal stem cells. However it is unknown whether they undergo a similar process of telomere shortening. In this study we show a more accentuated rate of telomere loss in leukocytes from pre term infants compared to human foetuses of comparable age followed longitudinally for 8-12 weeks in a longitudinal study. Our results point to a difference in HSC behaviour between foetal and early postnatal life which is independent of age but may be influenced by events at birth itself.

[Effects of postnatal growth retardation on early neurodevelopment in premature infants with intrauterine growth retardation].

PubMed

Cai, Yue-Ju; Song, Yan-Yan; Huang, Zhi-Jian; Li, Jian; Qi, Jun-Ye; Xiao, Xu-Wen; Wang, Lan-Xiu

2015-09-01

To study the effects of postnatal growth retardation on early neurodevelopment in premature infants with intrauterine growth retardation (IUGR). A retrospective analysis was performed on the clinical data of 171 premature infants who were born between May 2008 and May 2012 and were followed up until a corrected gestational age of 6 months. These infants were classified into two groups: IUGR group (n=40) and appropriate for gestational age (AGA) group (n=131). The growth retardation rates at the corrected gestational ages of 40 weeks, 3 months, and 6 months, as well as the neurodevelopmental outcome (evaluated by Gesell Developmental Scale) at corrected gestational ages of 3 and 6 months, were compared between the two groups. The growth retardation rate in the IUGR group was significantly higher than in the AGA group at the corrected gestational ages of 40 weeks, 3 months, and 6 months. All five developmental quotients evaluated by Gesell Developmental Scale (gross motor, fine motor, language, adaptability and individuality) in the IUGR group were significantly lower than in the AGA group at the corrected gestational ages of 3 months. At the corrected gestational age of 6 months, the developmental quotients of fine motor and language in the IUGR group were significantly lower than in the AGA group, however, there were no significant differences in the developmental quotients of gross motor, adaptability and individuality between the two groups. All five developmental quotients in IUGR infants with catch-up lag in weight were significantly lower than in IUGR and AGA infants who had caught up well. Growth retardation at early postnatal stages may adversely affect the early neurodevelopment in infants with IUGR.

Effects of xanthosine in isoform switch and splice variants of expressed genes in mammary epithelial cells

USDA-ARS?s Scientific Manuscript database

Although intramammary xanthosine (XS) treatment was reported to increase the mammary stem cell population and milk yield in bovine and caprine, underlying molecular mechanisms remain unclear. The goal of this study was to evaluate effects of XS treatment on the mammary transcriptome in early-lactati...

Analysis of Milk from Mothers Who Delivered Prematurely Reveals Few Changes in Proteases and Protease Inhibitors across Gestational Age at Birth and Infant Postnatal Age123

PubMed Central

Demers-Mathieu, Veronique; Nielsen, Søren Drud; Underwood, Mark A; Borghese, Robyn

2017-01-01

Background: Peptidomics research has demonstrated that protease activity is higher in breast milk from preterm-delivering mothers than from term-delivering mothers. However, to our knowledge, the effect of the degree of prematurity and postnatal age on proteases and protease inhibitors in human milk remains unknown. Objective: We aimed to determine the change of proteases and protease inhibitors in milk from mothers who delivered prematurely across gestational age (GA) and postnatal age. Methods: Milk samples were collected from 18 mothers aged 26–40 y who delivered preterm infants and who lacked mastitis. For analysis, samples were separated into 2 groups: 9 from early GA (EGA) (24–26 wk GA)-delivering mothers and 9 from late GA (LGA) (27–32 wk GA)-delivering mothers. Within the 9 samples in each group, the collection time ranged from postnatal days 2 to 47. The activity and predicted activity of proteases in preterm milk were determined with the use of fluorometric and spectrophotometric assays and peptidomics, respectively. Protease and protease inhibitor concentrations were determined with the use of ELISA. Linear mixed models were applied to compare enzymes across GA and postnatal age. Results: Carboxypeptidase B2, kallikrein, plasmin, elastase, thrombin, and cytosol aminopeptidase were present and active in the milk of preterm-delivering mothers. Most milk protease and antiprotease concentrations did not change with GA or postnatal age. However, the concentration and activity of kallikrein, the most abundant and active protease in preterm milk, increased by 25.4 ng · mL−1 · d−1 and 0.454 μg · mL−1 · d−1 postnatally, respectively, in EGA milk samples while remaining stable in LGA milk samples. Conclusions: This research demonstrates that proteases are active in human milk and begin to degrade milk protein within the mammary gland before consumption by infants. Proteases and protease inhibitors in milk from mothers of premature infants mostly

Genistein and resveratrol: mammary cancer chemoprevention and mechanisms of action in the rat.

PubMed

Whitsett, Timothy G; Lamartiniere, Coral A

2006-12-01

The environment, including diet, plays a critical role in a woman's subsequent risk of breast cancer. Two dietary polyphenols that have received attention from the health and research communities for their ability to protect against breast cancer are: genistein, a component of soy; and resveratrol, a phytoalexin found in red grapes and red wine. We and others have shown that both genistein and resveratrol can protect against mammary cancer in rodents. The timing of exposure to genistein appears critical for its mammary protective effects. It has been reported that genistein early in life causes enhanced mammary gland differentiation, alterations in cell proliferation and apoptosis, and upregulation of tumor-suppressor genes. With resveratrol in the diet, changes in cell proliferation and apoptosis in terminal ductal structures of the mammary gland might help to explain its protective effects. We conclude that genistein and resveratrol can protect against breast cancer by regulating important mammary growth and differentiation pathways.

Active retinitis in an infant with postnatally acquired cytomegalovirus infection.

PubMed

Piersigilli, F; Catena, G; De Gasperis, M R; Lozzi, S; Auriti, C

2012-07-01

Congenital cytomegalovirus (CMV) is frequently associated with active retinitis. In contrast, in the immunocompetent neonate with postnatally acquired CMV infection retinitis is rarely present and usually does not progress. We describe the case of an infant with postnatal CMV infection and active retinitis diagnosed at 20 days of life. Owing to the rapid progression of the retinitis, therapy with intravenous ganciclovir was performed, with prompt regression of the retinitis. Therapy was then continued with oral valganciclovir for one further week. Although very unusual, CMV retinitis has to be taken into consideration in neonates with early postnatally acquired CMV infection, as an early diagnosis and treatment may be crucial to avoid visual impairment.

Late emerging effects of prenatal and early postnatal nicotine exposure on the cholinergic system and anxiety-like behavior.

PubMed

Eppolito, Amy K; Bachus, Susan E; McDonald, Craig G; Meador-Woodruff, James H; Smith, Robert F

2010-01-01

Animal models of prenatal nicotine exposure clearly indicate that nicotine is a neuroteratogen. Some of the persisting effects of prenatal nicotine exposure include low birth weight, behavioral changes and deficits in cognitive function, although few studies have looked for neurobehavioral and neurochemical effects that might persist throughout the lifespan. Pregnant rats were given continuous infusions of nicotine (0.96mg/kg/day or 2.0mg/kg/day, freebase) continuing through the third trimester equivalent, a period of rapid brain development. Because the third trimester equivalent occurs postnatally in the rat (roughly the first week of life) nicotine administration to neonate pups continued via maternal milk until postnatal day (P) 10. Exposure to nicotine during pre- and early postnatal development had an anxiogenic effect on adult rats (P75) in the elevated plus maze (EPM), and blocked extinction learning in a fear conditioning paradigm, suggesting that pre- and postnatal nicotine exposure affect anxiety-like behavior and cognitive function well into adulthood. In contrast, nicotine exposure had no effect on anxiety-like behaviors in the EPM in adolescent animals (P30). Analysis of mRNA for the alpha4, alpha7, and beta2 subunits of nicotinic acetylcholine receptors revealed lower expression of these subunits in the adult hippocampus and medial prefrontal cortex following pre- and postnatal nicotine exposure, suggesting that nicotine altered the developmental trajectory of the brain. These long-term behavioral and neurochemical changes strengthen the case for discouraging cigarette smoking during pregnancy and clearly indicate that the use of the patch as a smoking cessation aid during pregnancy is not a safe alternative.

Mechanical strain induces involution-associated events in mammary epithelial cells

PubMed Central

Quaglino, Ana; Salierno, Marcelo; Pellegrotti, Jesica; Rubinstein, Natalia; Kordon, Edith C

2009-01-01

specifically designed for such a purpose. We believe that our results indicate the relevance of mechanical stress among the early post-lactation events that lead to mammary gland involution. PMID:19615079

Pleiotrophin (PTN) Expression and Function and in the Mouse Mammary Gland and Mammary Epithelial Cells

PubMed Central

Rosenfield, Sonia M.; Bowden, Emma T.; Cohen-Missner, Shani; Gibby, Krissa A.; Ory, Virginie; Henke, Ralf T.; Riegel, Anna T.; Wellstein, Anton

2012-01-01

Expression of the heparin-binding growth factor, pleiotrophin (PTN) in the mammary gland has been reported but its function during mammary gland development is not known. We examined the expression of PTN and its receptor ALK (Anaplastic Lymphoma Kinase) at various stages of mouse mammary gland development and found that their expression in epithelial cells is regulated in parallel during pregnancy. A 30-fold downregulation of PTN mRNA expression was observed during mid-pregnancy when the mammary gland undergoes lobular-alveolar differentiation. After weaning of pups, PTN expression was restored although baseline expression of PTN was reduced significantly in mammary glands of mice that had undergone multiple pregnancies. We found PTN expressed in epithelial cells of the mammary gland and thus used a monoclonal anti-PTN blocking antibody to elucidate its function in cultured mammary epithelial cells (MECs) as well as during gland development. Real-time impedance monitoring of MECs growth, migration and invasion during anti-PTN blocking antibody treatment showed that MECs motility and invasion but not proliferation depend on the activity of endogenous PTN. Increased number of mammospheres with laminin deposition after anti-PTN blocking antibody treatment of MECs in 3D culture and expression of progenitor markers suggest that the endogenously expressed PTN inhibits the expansion and differentiation of epithelial progenitor cells by disrupting cell-matrix adhesion. In vivo, PTN activity was found to inhibit ductal outgrowth and branching via the inhibition of phospho ERK1/2 signaling in the mammary epithelial cells. We conclude that PTN delays the maturation of the mammary gland by maintaining mammary epithelial cells in a progenitor phenotype and by inhibiting their differentiation during mammary gland development. PMID:23077670

Trehalose rescues glial cell dysfunction in striatal cultures from HD R6/1 mice at early postnatal development.

PubMed

Perucho, Juan; Gómez, Ana; Muñoz, María Paz; de Yébenes, Justo García; Mena, María Ángeles; Casarejos, María José

2016-07-01

The pathological hallmark of Huntington disease (HD) is the intracellular aggregation of mutant huntingtin (mHTT) in striatal neurons and glia associated with the selective loss of striatal medium-sized spiny neurons. Up to the present, the role of glia in HD is poorly understood and has been classically considered secondary to neuronal disorder. Trehalose is a disaccharide known to possess many pharmacological properties, acting as an antioxidant, a chemical chaperone, and an inducer of autophagy. In this study, we analyzed at an early postnatal development stage the abnormalities observed in striatal glial cell cultures of postnatal R6/1 mice (HD glia), under baseline and stressing conditions and the protective effects of trehalose. Our data demonstrate that glial HD alterations already occur at early stages of postnatal development. After 20 postnatal days in vitro, striatal HD glia cultures showed more reactive astrocytes with increased expression of glial fibrillary acidic protein (GFAP) but with less replication capacity, less A2B5(+) glial progenitors and more microglia than wild-type (WT) cultures. HD glia had lower levels of intracellular glutathione (GSH) and was more susceptible to H2O2 and epoxomicin insults. The amount of expressed GDNF and secreted mature-BDNF by HD astrocytes were much lower than by WT astrocytes. In addition, HD glial cultures showed a deregulation of the major proteolytic systems, the ubiquitin-proteasomal system (UPS), and the autophagic pathway. This produces a defective protein quality control, indicated by the elevated levels of ubiquitination and p62 protein. Interestingly, we show that trehalose, through its capacity to induce autophagy, inhibited p62/SQSTM1 accumulation and facilitated the degradation of cytoplasmic aggregates from mHTT and α-synuclein proteins. Trehalose also reduced microglia activation and reversed the disrupted cytoskeleton of astrocytes accompanied with an increase in the replication capacity. In

Expression of klotho mRNA and protein in rat brain parenchyma from early postnatal development into adulthood

PubMed Central

Clinton, Sarah M.; Glover, Matthew E.; Maltare, Astha; Laszczyk, Ann M.; Mehi, Stephen J.; Simmons, Rebecca K.; King, Gwendalyn D.

2013-01-01

Without the age-regulating protein klotho, mouse lifespan is shortened and the rapid onset of age-related disorders occurs. Conversely, overexpression of klotho extends mouse lifespan. Klotho is most abundant in kidney and expressed in a limited number of other organs, including the brain, where klotho levels are highest in choroid plexus. Reports vary on where klotho is expressed within the brain parenchyma, and no data is available as to whether klotho levels change across postnatal development. We used in situ hybridization to map klotho mRNA expression in the developing and adult rat brain and report moderate, widespread expression across grey matter regions. mRNA expression levels in cortex, hippocampus, caudate putamen, and amygdala decreased during the second week of life and then gradually rose to adult levels by postnatal day 21. Immunohistochemistry revealed a protein expression pattern similar to the mRNA results, with klotho protein expressed widely throughout the brain. Klotho protein co-localized with both the neuronal marker NeuN, as well as, oligodendrocyte marker olig2. These results provide the first anatomical localization of klotho mRNA and protein in rat brain parenchyma and demonstrate that klotho levels vary during early postnatal development. PMID:23838326

Abnormal neural precursor cell regulation in the early postnatal Fragile X mouse hippocampus.

PubMed

Sourial, Mary; Doering, Laurie C

2017-07-01

The regulation of neural precursor cells (NPCs) is indispensable for a properly functioning brain. Abnormalities in NPC proliferation, differentiation, survival, or integration have been linked to various neurological diseases including Fragile X syndrome. Yet, no studies have examined NPCs from the early postnatal Fragile X mouse hippocampus despite the importance of this developmental time point, which marks the highest expression level of FMRP, the protein missing in Fragile X, in the rodent hippocampus and is when hippocampal NPCs have migrated to the dentate gyrus (DG) to give rise to lifelong neurogenesis. In this study, we examined NPCs from the early postnatal hippocampus and DG of Fragile X mice (Fmr1-KO). Immunocytochemistry on neurospheres showed increased Nestin expression and decreased Ki67 expression, which collectively indicated aberrant NPC biology. Intriguingly, flow cytometric analysis of the expression of the antigens CD15, CD24, CD133, GLAST, and PSA-NCAM showed a decreased proportion of neural stem cells (GLAST + CD15 + CD133 + ) and an increased proportion of neuroblasts (PSA-NCAM + CD15 + ) in the DG of P7 Fmr1-KO mice. This was mirrored by lower expression levels of Nestin and the mitotic marker phospho-histone H3 in vivo in the P9 hippocampus, as well as a decreased proportion of cells in the G 2 /M phases of the P7 DG. Thus, the absence of FMRP leads to fewer actively cycling NPCs, coinciding with a decrease in neural stem cells and an increase in neuroblasts. Together, these results show the importance of FMRP in the developing hippocampal formation and suggest abnormalities in cell cycle regulation in Fragile X. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

The effects of prenatal and early postnatal tocotrienol-rich fraction supplementation on cognitive function development in male offspring rats.

PubMed

Nagapan, Gowri; Meng Goh, Yong; Shameha Abdul Razak, Intan; Nesaretnam, Kalanithi; Ebrahimi, Mahdi

2013-07-31

Recent findings suggest that the intake of specific nutrients during the critical period in early life influence cognitive and behavioural development profoundly. Antioxidants such as vitamin E have been postulated to be pivotal in this process, as vitamin E is able to protect the growing brain from oxidative stress. Currently tocotrienols are gaining much attention due to their potent antioxidant and neuroprotective properties. It is thus compelling to look at the effects of prenatal and early postnatal tocotrienols supplementation, on cognition and behavioural development among offsprings of individual supplemented with tocotrienols. Therefore, this study is aimed to investigate potential prenatal and early postnatal influence of Tocotrienol-Rich Fraction (TRF) supplementation on cognitive function development in male offspring rats. Eight-week-old adult female Sprague Dawley (SD) rats were randomly assigned into five groups of two animals each. The animals were fed either with the base diet as control (CTRL), base diet plus vehicle (VHCL), base diet plus docosahexanoic acid (DHA), base diet plus Tocotrienol-Rich fraction (TRF), and base diet plus both docosahexaenoic acid, and tocotrienol rich fraction (DTRF) diets for 2 weeks prior to mating. The females (F0 generation) were maintained on their respective treatment diets throughout the gestation and lactation periods. Pups (F1 generation) derived from these dams were raised with their dams from birth till four weeks post natal. The male pups were weaned at 8 weeks postnatal, after which they were grouped into five groups of 10 animals each, and fed with the same diets as their dams for another eight weeks. Learning and behavioural experiments were conducted only in male off-spring rats using the Morris water maze. Eight-week-old adult female Sprague Dawley (SD) rats were randomly assigned into five groups of two animals each. The animals were fed either with the base diet as control (CTRL), base diet plus

Postnatal BMI changes in children with different birthweights: A trial study for detecting early predictive factors for pediatric obesity

PubMed Central

Nakagawa, Yuichi; Nakanishi, Toshiki; Satake, Eiichiro; Matsushita, Rie; Saegusa, Hirokazu; Kubota, Akira; Natsume, Hiromune; Shibata, Yukinobu; Fujisawa, Yasuko

2018-01-01

Abstract. The purpose of this study was to clarify the degree of early postnatal growth by birthweight and detect early predictive factors for pediatric obesity. Body mass index (BMI) and degree of obesity were examined in children in the fourth year of elementary school and second year of junior high school. Their BMI at birth and three years of age were also examined. Based on birthweight, participants were divided into three groups: low (< 2500 g), middle (2500–3500 g), and high (> 3500 g). Furthermore, according to the degree of obesity, they were divided into two groups: obese (20% ≤) and non-obese (20% >). The change of BMI from birth to three years of age (ΔBMI) showed a strong inverse relationship with birthweight and was significantly different among the three birthweight groups (low > middle > high). The ΔBMI and BMI at three years of age were higher in obese than in non-obese children and showed significant positive correlations with the degree of obesity. Early postnatal growth might be determined by birthweight and was higher in obese than in non-obese children. The ΔBMI from birth to three years of age and BMI at age of three years could be predictive factors for pediatric obesity. PMID:29403153

Short-term exposure to pregnancy levels of estrogen prevents mammary carcinogenesis

PubMed Central

Rajkumar, Lakshmanaswamy; Guzman, Raphael C.; Yang, Jason; Thordarson, Gudmundur; Talamantes, Frank; Nandi, Satyabrata

2001-01-01

It is well established that pregnancy early in life reduces the risk of breast cancer in women and that this effect is universal. This phenomenon of parity protection against mammary cancer is also observed in rodents. Earlier studies have demonstrated that short-term administration of estradiol (E) in combination with progesterone mimics the protective effect of parity in rats. In this study, the lowest effective E dosage for preventing mammary cancer was determined. Rats were injected with N-methyl-N-nitrosourea at 7 weeks of age; 2 weeks later, the rats were subjected to sustained treatment with 20 μg, 100 μg, 200 μg, or 30 mg of E in silastic capsules for 3 weeks. Treatments with 100 μg, 200 μg, and 30 mg of E resulted in serum levels of E equivalent to those of pregnancy and were highly effective in preventing mammary cancer. E treatment (20 μg) did not result in pregnancy levels of E and was not effective in reducing the mammary cancer incidence. In another set of experiments, we determined the effect of different durations of E with or without progesterone treatments on mammary carcinogenesis. These experiments indicate that a period as short as one-third the period of gestation is sufficient to induce protection against mammary carcinogenesis. The pioneering aspect of our study in contrast to long-term estrogen exposure, which is thought to increase the risk of breast cancer, is that short-term sustained treatments with pregnancy levels of E can induce protection against frank mammary cancer. PMID:11573010

Risk factors for antenatal depression, postnatal depression and parenting stress

PubMed Central

Leigh, Bronwyn; Milgrom, Jeannette

2008-01-01

Background Given that the prevalence of antenatal and postnatal depression is high, with estimates around 13%, and the consequences serious, efforts have been made to identify risk factors to assist in prevention, identification and treatment. Most risk factors associated with postnatal depression have been well researched, whereas predictors of antenatal depression have been less researched. Risk factors associated with early parenting stress have not been widely researched, despite the strong link with depression. The aim of this study was to further elucidate which of some previously identified risk factors are most predictive of three outcome measures: antenatal depression, postnatal depression and parenting stress and to examine the relationship between them. Methods Primipara and multiparae women were recruited antenatally from two major hoitals as part of the beyondblue National Postnatal Depression Program [1]. In this subsidiary study, 367 women completed an additional large battery of validated questionnaires to identify risk factors in the antenatal period at 26–32 weeks gestation. A subsample of these women (N = 161) also completed questionnaires at 10–12 weeks postnatally. Depression level was measured by the Beck Depression Inventory (BDI). Results Regression analyses identified significant risk factors for the three outcome measures. (1). Significant predictors for antenatal depression: low self-esteem, antenatal anxiety, low social support, negative cognitive style, major life events, low income and history of abuse. (2). Significant predictors for postnatal depression: antenatal depression and a history of depression while also controlling for concurrent parenting stress, which was a significant variable. Antenatal depression was identified as a mediator between seven of the risk factors and postnatal depression. (3). Postnatal depression was the only significant predictor for parenting stress and also acted as a mediator for other risk factors

Risk factors for antenatal depression, postnatal depression and parenting stress.

PubMed

Leigh, Bronwyn; Milgrom, Jeannette

2008-04-16

Given that the prevalence of antenatal and postnatal depression is high, with estimates around 13%, and the consequences serious, efforts have been made to identify risk factors to assist in prevention, identification and treatment. Most risk factors associated with postnatal depression have been well researched, whereas predictors of antenatal depression have been less researched. Risk factors associated with early parenting stress have not been widely researched, despite the strong link with depression. The aim of this study was to further elucidate which of some previously identified risk factors are most predictive of three outcome measures: antenatal depression, postnatal depression and parenting stress and to examine the relationship between them. Primipara and multiparae women were recruited antenatally from two major hoitals as part of the beyondblue National Postnatal Depression Program 1. In this subsidiary study, 367 women completed an additional large battery of validated questionnaires to identify risk factors in the antenatal period at 26-32 weeks gestation. A subsample of these women (N = 161) also completed questionnaires at 10-12 weeks postnatally. Depression level was measured by the Beck Depression Inventory (BDI). Regression analyses identified significant risk factors for the three outcome measures. (1). Significant predictors for antenatal depression: low self-esteem, antenatal anxiety, low social support, negative cognitive style, major life events, low income and history of abuse. (2). Significant predictors for postnatal depression: antenatal depression and a history of depression while also controlling for concurrent parenting stress, which was a significant variable. Antenatal depression was identified as a mediator between seven of the risk factors and postnatal depression. (3). Postnatal depression was the only significant predictor for parenting stress and also acted as a mediator for other risk factors. Risk factor profiles for

Effect of insulin-like growth factor-I during the early postnatal period in intrauterine growth-restricted rats.

PubMed

Ikeda, Naho; Shoji, Hiromichi; Suganuma, Hiroki; Ohkawa, Natsuki; Kantake, Masato; Murano, Yayoi; Sakuraya, Koji; Shimizu, Toshiaki

2016-05-01

Insulin-like growth factor-I (IGF-I) is essential for perinatal growth and development; low serum IGF-I has been observed during intrauterine growth restriction (IUGR). We investigated the effects of recombinant human (rh) IGF-I in IUGR rats during the early postnatal period. Intrauterine growth restriction was induced by bilateral uterine artery ligation in pregnant rats. IUGR pups were divided into two groups injected daily with rhIGF-I (2 mg/kg; IUGR/IGF-I, n = 16) or saline (IUGR/physiologic saline solution (PSS), n = 16) from postnatal day (PND) 7 to 13. Maternal sham-operated pups injected with saline were used as controls (control, n = 16). Serum IGF-I and IGF binding proteins (IGFBP) 3 and 5 were measured on PND25. The expression of Igf-i, IGF-I receptor (Igf-ir), Igfbp3, and 5 mRNA in the liver and brain was measured using real-time polymerase chain reaction on PND25. Immunohistochemical staining of the liver for IGF expression was performed. Mean bodyweight on PND3 and PND25 in the IUGR pups (IUGR/IGF-I and IUGR/PSS) was significantly lower than that of the control pups. Serum IGF-I and hepatic Igf-ir mRNA in the IUGR pups were significantly lower than those in the control pups. In the IUGR/IGF-I group, hepatic Igfbp3 mRNA and liver immunohistochemical staining were increased. In the IUGR/PSS and control pups, there were no significant differences between these two groups in serum IGFBP3 and IGFBP5, hepatic Igf-i and Igfbp-5 mRNA, or brain Igf mRNA. No benefits on body and brain weight gain but an effective increase in hepatic IGFBP-3 was observed after treatment with 2 mg/kg rhIGF-I during the early postnatal period. © 2015 Japan Pediatric Society.

Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life

PubMed Central

Smith, Dani; Aherrera, Angela; Lopez, Armando; Neptune, Enid; Winickoff, Jonathan P.; Klein, Jonathan D.; Chen, Gang; Lazarus, Philip; Collaco, Joseph M.; McGrath-Morrow, Sharon A.

2015-01-01

Nicotine exposure has been associated with an increased likelihood of developing attention deficit hyperactivity disorder (ADHD) in offspring of mothers who smoked during pregnancy. The goal of this study was to determine if exposure to E-cigarette nicotine vapors during late prenatal and early postnatal life altered behavior in adult mice. Methods Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains. Results Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not. Conclusion Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth. PMID:26372012

Mouse Mammary Tumor Virus c-rel Transgenic Mice Develop Mammary Tumors

PubMed Central

Romieu-Mourez, Raphaëlle; Kim, Dong W.; Min Shin, Sang; Demicco, Elizabeth G.; Landesman-Bollag, Esther; Seldin, David C.; Cardiff, Robert D.; Sonenshein, Gail E.

2003-01-01

Amplification, overexpression, or rearrangement of the c-rel gene, encoding the c-Rel NF-κB subunit, has been reported in solid and hematopoietic malignancies. For example, many primary human breast cancer tissue samples express high levels of nuclear c-Rel. While the Rev-T oncogene v-rel causes tumors in birds, the ability of c-Rel to transform in vivo has not been demonstrated. To directly test the role of c-Rel in breast tumorigenesis, mice were generated in which overexpression of mouse c-rel cDNA was driven by the hormone-responsive mouse mammary tumor virus long terminal repeat (MMTV-LTR) promoter, and four founder lines identified. In the first cycle of pregnancy, the expression of transgenic c-rel mRNA was observed, and levels of c-Rel protein were increased in the mammary gland. Importantly, 31.6% of mice developed one or more mammary tumors at an average age of 19.9 months. Mammary tumors were of diverse histology and expressed increased levels of nuclear NF-κB. Analysis of the composition of NF-κB complexes in the tumors revealed aberrant nuclear expression of multiple subunits, including c-Rel, p50, p52, RelA, RelB, and the Bcl-3 protein, as observed previously in human primary breast cancers. Expression of the cancer-related NF-κB target genes cyclin D1, c-myc, and bcl-xl was significantly increased in grossly normal transgenic mammary glands starting the first cycle of pregnancy and increased further in mammary carcinomas compared to mammary glands from wild-type mice or virgin transgenic mice. In transient transfection analysis in untransformed breast epithelial cells, c-Rel-p52 or -p50 heterodimers either potently or modestly induced cyclin D1 promoter activity, respectively. Lastly, stable overexpression of c-Rel resulted in increased cyclin D1 and NF-κB p52 and p50 subunit protein levels. These results indicate for the first time that dysregulated expression of c-Rel, as observed in breast cancers, is capable of contributing to mammary

Prenatal and early postnatal NOAEL-dose clothianidin exposure leads to a reduction of germ cells in juvenile male mice

PubMed Central

YANAI, Shogo; HIRANO, Tetsushi; OMOTEHARA, Takuya; TAKADA, Tadashi; YONEDA, Naoki; KUBOTA, Naoto; YAMAMOTO, Anzu; MANTANI, Youhei; YOKOYAMA, Toshifumi; KITAGAWA, Hiroshi; HOSHI, Nobuhiko

2017-01-01

Neonicotinoids are pesticides used worldwide. They bind to insect nicotinic acetylcholine receptors (nAChRs) with high affinity. We previously reported that clothianidin (CTD), one of the latest neonicotinoids, reduced antioxidant expression and induced germ cell death in the adult testis of vertebrates. Here, we investigated the male reproductive toxicity of prenatal and early postnatal exposure to CTD, because it is likely that developmental exposure more severely affects the testis compared to adults due to the absence of the blood-testis barrier. Pregnant C57BL/6 mice were given water gel blended with CTD (0, 10 or 50 mg/kg/day; no-observed-adverse-effect-level [NOAEL for mice]: 47.2 mg/kg/day) between gestational day 1 and 14 days post-partum. We then examined the testes of male offspring at postnatal day 14. The testis weights and the numbers of germ cells per seminiferous tubule were decreased in the CTD-50 group, and abnormal tubules containing no germ cells appeared. Nevertheless, the apoptotic cell number and proliferative activity were not significantly different between the control and CTD-exposed groups. There were no significant differences in the androgen-related parameters, such as the Leydig cell volume per testis, the Sertoli cell number and the tubule diameter. The present study is the first demonstration that in utero and lactational exposures to CTD at around the NOAEL for mice reduce the germ cell number, but our findings suggest that these exposures do not affect steroidogenesis in Leydig cells during prenatal or early postnatal life. PMID:28579575

Early postnatal weight gain as a predictor for the development of retinopathy of prematurity.

PubMed

Biniwale, Manoj; Weiner, Angela; Sardesai, Smeeta; Cayabyab, Rowena; Barton, Lorayne; Ramanathan, Rangasamy

2017-10-01

The objective of this study is to validate the reliability of early postnatal weight gain as an accurate predictor of type 1 retinopathy of prematurity (ROP) requiring treatment in a large predominantly Hispanic US cohort with the use of an online tool called WINROP (weight, neonatal retinopathy of prematurity (IGF-1), neonatal retinopathy of prematurity). Retrospective cohort study consisted of preterm infants <32 weeks gestation and birth weight <1500 g. Weekly weights to 36 weeks post-menstrual age or discharge if earlier were entered into the WINROP tool. This tool generated alarm and risk indicator for developing ROP. The infants with type 1 ROP requiring treatment as well as all stages of ROP were compared with the alarms and risks generated by WINROP tool. A total of 492 infants were entered into the WINROP tool. The infants who developed type 1 ROP requiring treatment, the WINROP tool detected 80/89 (90%) at less than 32 weeks gestation. Nine infants developed type 1 ROP were classified as low risk and did not alarm. Postnatal weight gain alone, in predominantly Hispanic US population, predicted type 1 ROP requiring treatment before 32 weeks of gestation in infants with a sensitivity of 90%. The tool appeared to identify majority of affected infants much earlier than the scheduled screening.

Effects of xanthosine on gene expression of mammary epithelial cells using RNA sequencing of goat milk fat globules

USDA-ARS?s Scientific Manuscript database

Although intramammary xanthosine (XS) treatment was reported to increase the mammary stem cell population and milk yield in bovine and caprine, underlying molecular mechanisms remain unclear. The goal of this study was to evaluate effects of XS treatment on the mammary transcriptome in early lactati...

Early intervention to protect the mother-infant relationship following postnatal depression: study protocol for a randomised controlled trial.

PubMed

Milgrom, Jeannette; Holt, Charlene

2014-10-03

postnatal depression group treatment programme. Primary outcome measures are the Parenting Stress Index (self-report measure) and the Parent-child Early Relational Assessment (observational measure coded by a blinded observer). Measurements are taken at baseline, after the postnatal depression programme, post-HUGS/Playtime, and at 6 months post-HUGS/Playtime. This research addresses the need for specific treatment for mother-infant interactional difficulties following postnatal depression. There is a need to investigate interventions in randomised trials to prevent detrimental effects on child development and make available evidence-based treatments. Australia and New Zealand Clinical Trials Register: ACTRN12612001110875. Date Registered: 17 October 2012.

The effects of prenatal and early postnatal tocotrienol-rich fraction supplementation on cognitive function development in male offspring rats

PubMed Central

2013-01-01

Background Recent findings suggest that the intake of specific nutrients during the critical period in early life influence cognitive and behavioural development profoundly. Antioxidants such as vitamin E have been postulated to be pivotal in this process, as vitamin E is able to protect the growing brain from oxidative stress. Currently tocotrienols are gaining much attention due to their potent antioxidant and neuroprotective properties. It is thus compelling to look at the effects of prenatal and early postnatal tocotrienols supplementation, on cognition and behavioural development among offsprings of individual supplemented with tocotrienols. Therefore, this study is aimed to investigate potential prenatal and early postnatal influence of Tocotrienol-Rich Fraction (TRF) supplementation on cognitive function development in male offspring rats. Eight-week-old adult female Sprague Dawley (SD) rats were randomly assigned into five groups of two animals each. The animals were fed either with the base diet as control (CTRL), base diet plus vehicle (VHCL), base diet plus docosahexanoic acid (DHA), base diet plus Tocotrienol-Rich fraction (TRF), and base diet plus both docosahexaenoic acid, and tocotrienol rich fraction (DTRF) diets for 2 weeks prior to mating. The females (F0 generation) were maintained on their respective treatment diets throughout the gestation and lactation periods. Pups (F1 generation) derived from these dams were raised with their dams from birth till four weeks post natal. The male pups were weaned at 8 weeks postnatal, after which they were grouped into five groups of 10 animals each, and fed with the same diets as their dams for another eight weeks. Learning and behavioural experiments were conducted only in male off-spring rats using the Morris water maze.Eight-week-old adult female Sprague Dawley (SD) rats were randomly assigned into five groups of two animals each. The animals were fed either with the base diet as control (CTRL), base

Intestinal absorption and renal reabsorption of calcium throughout postnatal development

PubMed Central

Beggs, Megan R

2017-01-01

Calcium is vital for many physiological functions including bone mineralization. Postnatal deposition of calcium into bone is greatest in infancy and continues through childhood and adolescence until peek mineral density is reached in early adulthood. Thereafter, bone mineral density remains static until it eventually declines in later life. A positive calcium balance, i.e. more calcium absorbed than excreted, is crucial to bone deposition during growth and thus to peek bone mineral density. Dietary calcium is absorbed from the intestine into the blood. It is then filtered by the renal glomerulus and either reabsorbed by the tubule or excreted in the urine. Calcium can be (re)absorbed across intestinal and renal epithelia via both transcellular and paracellular pathways. Current evidence suggests that significant intestinal and renal calcium transport changes occur throughout development. However, the molecular details of these alterations are incompletely delineated. Here we first briefly review the current model of calcium transport in the intestine and renal tubule in the adult. Then, we describe what is known with regard to calcium handling through postnatal development, and how alterations may aid in mediating a positive calcium balance. The role of transcellular and paracellular calcium transport pathways and the contribution of specific intestinal and tubular segments vary with age. However, the current literature highlights knowledge gaps in how specifically intestinal and renal calcium (re)absorption occurs early in postnatal development. Future research should clarify the specific changes in calcium transport throughout early postnatal development including mediators of these alterations enabling appropriate bone mineralization. Impact statement This mini review outlines the current state of knowledge pertaining to the molecules and mechanisms maintaining a positive calcium balance throughout postnatal development. This process is essential to achieving

Cognition and behavioural development in early childhood: the role of birth weight and postnatal growth

PubMed Central

Huang, Cheng; Martorell, Reynaldo; Ren, Aiguo; Li, Zhiwen

2013-01-01

Background We evaluate the relative importance of birth weight and postnatal growth for cognition and behavioural development in 8389 Chinese children, 4–7 years of age. Method Weight was the only size measure available at birth. Weight, height, head circumference and intelligence quotient (IQ) were measured between 4 and 7 years of age. Z-scores of birth weight and postnatal conditional weight gain to 4–7 years, as well as height and head circumference at 4–7 years of age, were the exposure variables. Z-scores of weight at 4–7 years were regressed on birth weight Z-scores, and the residual was used as the measure of postnatal conditional weight gain. The outcomes were child’s IQ, measured by the Chinese Wechsler Young Children Scale of Intelligence, as well as internalizing behavioural problems, externalizing behavioural problems and other behavioural problems, evaluated by the Child Behavior Checklist 4–18. Multivariate regressions were conducted to investigate the relationship of birth weight and postnatal growth variables with the outcomes, separately for preterm children and term children. Results Both birth weight and postnatal weight gain were associated with IQ among term children; 1 unit increment in Z-score of birth weight (∼450 g) was associated with an increase of 1.60 [Confidence interval (CI): 1.18–2.02; P < 0.001] points in IQ, and 1 unit increment in conditional postnatal weight was associated with an increase of 0.46 (CI: 0.06–0.86; P = 0.02) points in IQ, after adjustment for confounders; similar patterns were observed when Z-scores of postnatal height and head circumference at age 4–7 years were used as alternative measurements of postnatal growth. Effect sizes of relationships with IQ were smaller than 0.1 of a standard deviation in all cases. Neither birth weight nor postnatal growth indicators were associated with behavioural outcomes among term children. In preterm children, neither birth weight nor postnatal growth

Cognition and behavioural development in early childhood: the role of birth weight and postnatal growth.

PubMed

Huang, Cheng; Martorell, Reynaldo; Ren, Aiguo; Li, Zhiwen

2013-02-01

We evaluate the relative importance of birth weight and postnatal growth for cognition and behavioural development in 8389 Chinese children, 4-7 years of age. Method Weight was the only size measure available at birth. Weight, height, head circumference and intelligence quotient (IQ) were measured between 4 and 7 years of age. Z-scores of birth weight and postnatal conditional weight gain to 4-7 years, as well as height and head circumference at 4-7 years of age, were the exposure variables. Z-scores of weight at 4-7 years were regressed on birth weight Z-scores, and the residual was used as the measure of postnatal conditional weight gain. The outcomes were child's IQ, measured by the Chinese Wechsler Young Children Scale of Intelligence, as well as internalizing behavioural problems, externalizing behavioural problems and other behavioural problems, evaluated by the Child Behavior Checklist 4-18. Multivariate regressions were conducted to investigate the relationship of birth weight and postnatal growth variables with the outcomes, separately for preterm children and term children. Both birth weight and postnatal weight gain were associated with IQ among term children; 1 unit increment in Z-score of birth weight (∼450 g) was associated with an increase of 1.60 [Confidence interval (CI): 1.18-2.02; P < 0.001] points in IQ, and 1 unit increment in conditional postnatal weight was associated with an increase of 0.46 (CI: 0.06-0.86; P = 0.02) points in IQ, after adjustment for confounders; similar patterns were observed when Z-scores of postnatal height and head circumference at age 4-7 years were used as alternative measurements of postnatal growth. Effect sizes of relationships with IQ were smaller than 0.1 of a standard deviation in all cases. Neither birth weight nor postnatal growth indicators were associated with behavioural outcomes among term children. In preterm children, neither birth weight nor postnatal growth measures were associated with IQ or

VHL deletion impairs mammary alveologenesis but is not sufficient for mammary tumorigenesis.

PubMed

Seagroves, Tiffany N; Peacock, Danielle L; Liao, Debbie; Schwab, Luciana P; Krueger, Robin; Handorf, Charles R; Haase, Volker H; Johnson, Randall S

2010-05-01

Overexpression of hypoxia inducible factor-1 (HIF-1)alpha, which is common in most solid tumors, correlates with poor prognosis and high metastatic risk in breast cancer patients. Because HIF-1alpha protein stability is tightly controlled by the tumor suppressor von Hippel-Lindau (VHL), deletion of VHL results in constitutive HIF-1alpha expression. To determine whether VHL plays a role in normal mammary gland development, and if HIF-1alpha overexpression is sufficient to initiate breast cancer, Vhl was conditionally deleted in the mammary epithelium using the Cre/loxP system. During first pregnancy, loss of Vhl resulted in decreased mammary epithelial cell proliferation and impaired alveolar differentiation; despite these phenotypes, lactation was sufficient to support pup growth. In contrast, in multiparous dams, Vhl(-/-) mammary glands exhibited a progressive loss of alveolar epithelium, culminating in lactation failure. Deletion of Vhl in the epithelium also impacted the mammary stroma, as there was increased microvessel density accompanied by hemorrhage and increased immune cell infiltration. However, deletion of Vhl was not sufficient to induce mammary tumorigenesis in dams bred continuously for up to 24 months of age. Moreover, co-deletion of Hif1a could not rescue the Vhl(-/-)-dependent phenotype as dams were unable to successfully lactate during the first lactation. These results suggest that additional VHL-regulated genes besides HIF1A function to maintain the proliferative and regenerative potential of the breast epithelium.

Effects of the Insulin-like Growth Factor Pathway on the Regulation of Mammary Gland Development.

PubMed

Ha, Woo Tae; Jeong, Ha Yeon; Lee, Seung Yoon; Song, Hyuk

2016-09-01

The insulin-like growth factor (IGF) pathway is a key signal transduction pathway involved in cell proliferation, migration, and apoptosis. In dairy cows, IGF family proteins and binding receptors, including their intracellular binding partners, regulate mammary gland development. IGFs and IGF receptor interactions in mammary glands influence the early stages of mammogenesis, i.e., mammary ductal genesis until puberty. The IGF pathway includes three major components, IGFs (such as IGF-I, IGF-II, and insulin), their specific receptors, and their high-affinity binding partners (IGF binding proteins [IGFBPs]; i.e., IGFBP1-6), including specific proteases for each IGFBP. Additionally, IGFs and IGFBP interactions are critical for the bioactivities of various intracellular mechanisms, including cell proliferation, migration, and apoptosis. Notably, the interactions between IGFs and IGFBPs in the IGF pathway have been difficult to characterize during specific stages of bovine mammary gland development. In this review, we aim to describe the role of the interaction between IGFs and IGFBPs in overall mammary gland development in dairy cows.

Identification of conserved microRNAs in peripheral blood from giant panda: expression of mammary gland-related microRNAs during late pregnancy and early lactation.

PubMed

Wang, C D; Long, K; Jin, L; Huang, S; Li, D H; Ma, X P; Wei, M; Gu, Y; Ma, J D; Zhang, H

2015-11-13

The giant panda (Ailuropoda melanoleuca) is one of the world's most endangered mammals, and it has evolved several unusual biological and behavioral traits. During puberty, pregnancy, lactation, and involution, the mammary gland undergoes profound morphological and functional changes. A large number of microRNAs (miRNAs) have been identified to be involved in mammary gland development and lactation. In this study, we identified 202 conserved mature miRNAs, corresponding to 147 pre-miRNAs, in giant panda peripheral blood using a small RNA-sequencing approach. In addition, 27 miRNA families and 29 miRNA clusters were identified. We analyzed the arm selection preference of pre-miRNAs and found that: 1) most giant panda pre-miRNAs generated one-strand miRNAs, and the 5p-arm only miRNAs have a higher expression level than 3p-arm only miRNAs; 2) there were more 5p-arm dominant miRNAs than 3p-arm dominant miRNAs; and 3) 5p-arm dominant miRNAs have a larger fold change within miRNA pairs than 3p-arm dominant miRNAs. Expression of 12 lactation-related miRNAs was detected across late pregnancy and early lactation stages by qPCR, and seven miRNAs were identified as clustered in one significant model. Most of these clustered miRNAs exhibited inhibitory roles in proliferation and differentiation of mammary epithelial cells. Functional analysis highlighted important roles of the seven as signed miRNAs in mammary development and metabolic changes, including blood vessel morphogenesis, macromolecule biosynthesis, cell cycle regulation, and protein transport.

Massage therapy during early postnatal life promotes greater lean mass and bone growth, mineralization, and strength in juvenile and young adult rats.

PubMed

Chen, H; Miller, S; Shaw, J; Moyer-Mileur, L

2009-01-01

The objects of this study were to investigate the effects of massage therapy during early life on postnatal growth, body composition, and skeletal development in juvenile and young adult rats. Massage therapy was performed for 10 minutes daily from D6 to D10 of postnatal life in rat pups (MT, n=24). Body composition, bone area, mineral content, and bone mineral density were measured by dual energy X-ray absorptiometry (DXA); bone strength and intrinsic stiffness on femur shaft were tested by three-point bending; cortical and cancellous bone histomorphometric measurements were performed at D21 and D60. Results were compared to age- and gender-matched controls (C, n=24). D21 body weight, body length, lean mass, and bone area were significantly greater in the MT cohort. Greater bone mineral content was found in male MT rats; bone strength and intrinsic stiffness were greater in D60 MT groups. At D60 MT treatment promoted bone mineralization by increasing trabecular mineral apposition rate in male and endosteal mineral surface in females, and also improved micro-architecture by greater trabeculae width in males and decreasing trabecular separation in females. In summary, massage therapy during early life elicited immediate and prolonged anabolic effects on postnatal growth, lean mass and skeletal developmental in a gender-specific manner in juvenile and young adult rats.

Early host response in the mammary gland after experimental Streptococcus uberis challenge in heifers.

PubMed

de Greeff, Astrid; Zadoks, Ruth; Ruuls, Lisette; Toussaint, Mathilda; Nguyen, Thi Kim Anh; Downing, Alison; Rebel, Johanna; Stockhofe-Zurwieden, Norbert; Smith, Hilde

2013-06-01

Streptococcus uberis is a highly prevalent causative agent of bovine mastitis, which leads to large economic losses in the dairy industry. The aim of this study was to examine the host response during acute inflammation after experimental challenge with capsulated Strep. uberis. Gene expression in response to Strep. uberis was compared between infected and control quarters in 3 animals. All quarters (n=16) were sampled at 16 different locations. Microarray data showed that 239 genes were differentially expressed between infected and control quarters. No differences in gene expression were observed between the different locations. Microarray data were confirmed for several genes using quantitative PCR analysis. Genes differentially expressed due to early Strep. uberis mastitis represented several stages of the process of infection: (1) pathogen recognition; (2) chemoattraction of neutrophils; (3) tissue repair mechanisms; and (4) bactericidal activity. Three different pathogen recognition genes were induced: ficolins, lipopolysaccharide binding protein, and toll-like receptor 2. Calgranulins were found to be the most strongly upregulated genes during early inflammation. By histology and immunohistochemistry, we demonstrated that changes in gene expression in response to Strep. uberis were induced both in infiltrating somatic milk cells and in mammary epithelial cells, demonstrating that the latter cell type plays a role in milk production as well as immune responsiveness. Given the rapid development of inflammation or mastitis after infection, early diagnosis of (Strep. uberis) mastitis is required for prevention of disease and spread of the pathogen. Insight into host responses could help to design immunomodulatory therapies to dampen inflammation after (early) diagnosis of Strep. uberis mastitis. Future research should focus on development of these early diagnostics and immunomodulatory components for mastitis treatment. Copyright © 2013 American Dairy Science

Characterization of Human Mammary Epithelial Stem Cells

DTIC Science & Technology

2010-10-01

This term reflects the method used to detect murine mammary stem cells which is based on their individual ability to regenerate an entire mammary tree......mammary stem cells. We now describe a method for detecting an analogous subpopulation in normal human mammary tissue. Dissociated cells are suspended

Prenatal and Early Postnatal Environmental Enrichment Reduce Acute Cell Death and Prevent Neurodevelopment and Memory Impairments in Rats Submitted to Neonatal Hypoxia Ischemia.

PubMed

Durán-Carabali, L E; Arcego, D M; Odorcyk, F K; Reichert, L; Cordeiro, J L; Sanches, E F; Freitas, L D; Dalmaz, C; Pagnussat, A; Netto, C A

2018-05-01

Environmental enrichment (EE) is an experimental strategy to attenuate the negative effects of different neurological conditions including neonatal hypoxia ischemia encephalopathy (HIE). The aim of the present study was to investigate the influence of prenatal and early postnatal EE in animals submitted to neonatal HIE model at postnatal day (PND) 3. Wistar rats were housed in EE or standard conditions (SC) during pregnancy and lactation periods. Pups of both sexes were assigned to one of four experimental groups, considering the early environmental conditions and the injury: SC-Sham, SC-HIE, EE-sham, and EE-HIE. The offspring were euthanized at two different time points: 48 h after HIE for biochemical analyses or at PND 67 for histological analyses. Behavioral tests were performed at PND 7, 14, 21, and 60. Offspring from EE mothers had better performance in neurodevelopmental and spatial memory tests when compared to the SC groups. HIE animals showed a reduction of IGF-1 and VEGF in the parietal cortex, but no differences in BDNF and TrkB levels were found. EE-HIE animals showed reduction in cell death, lower astrocyte reactivity, and an increase in AKTp levels in the hippocampus and parietal cortex. In addition, the EE was also able to prevent the hippocampus tissue loss. Altogether, present findings point to the protective potential of the prenatal and early postnatal EE in attenuating molecular and histological damage, as well as the neurodevelopmental impairments and the cognitive deficit, caused by HIE insult at PND 3.

Early postnatal response of the spinal nucleus of the bulbocavernosus and target muscles to testosterone in male gerbils.

PubMed

Hadi Mansouri, S; Siegford, Janice M; Ulibarri, Catherine

2003-05-14

This study examined the response of the spinal nucleus of the bulbocavernosus (SNB) and the bulbocavernosus (BC) muscle, to testosterone in male Mongolian gerbils (Meriones unguiculatus) during the early postnatal period. Male gerbil pups were given testosterone propionate (TP) or vehicle for 2 days, then perfused on postnatal day (PND) 3, 5, 10 or 15. The BC and levator ani (LA) muscles were removed, weighed, and sectioned. Cross-sections of BC muscle fibers were measured and muscle fiber morphology examined. Spinal cords were removed and coronally sectioned in order to count and measure the SNB motoneurons. Following TP treatment, male pups of all ages had significantly heavier BC-LA muscles and larger fibers in the BC muscle compared to age-matched controls. The increase in muscle weight following TP treatment was greatest at PND10, while fiber size increased to a similar degree at all ages suggesting that hyperplasia as well as hypertrophy was responsible for the increase in muscle mass at this time. SNB motoneurons increased significantly in number and size with age and TP treatment. We hypothesize that the increase in SNB motoneuron number during normal ontogeny that can be augmented by TP treatment and represents an unusual means of establishing sexual dimorphism in the nervous system of a mammal through cell recruitment to the motor pool of a postnatal animal.

Early (< 8 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants.

PubMed

Doyle, Lex W; Cheong, Jeanie L; Ehrenkranz, Richard A; Halliday, Henry L

2017-10-24

Bronchopulmonary dysplasia remains a major problem in neonatal intensive care units. Persistent inflammation in the lungs is the most likely underlying pathogenesis. Corticosteroids have been used to prevent or treat bronchopulmonary dysplasia because of their potent anti-inflammatory effects. To examine the relative benefits and adverse effects of systemic postnatal corticosteroids commenced within the first seven days of life for preterm infants at risk of developing bronchopulmonary dysplasia. For the 2017 update, we used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1); MEDLINE via PubMed (January 2013 to 21 February 2017); Embase (January 2013 to 21 February 2017); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 2013 to 21 February 2017). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials. For this review, we selected RCTs examining systemic postnatal corticosteroid treatment within the first seven days of life (early) in high-risk preterm infants. Most studies evaluated the use of dexamethasone, but we also included studies that assessed hydrocortisone, even when used primarily for management of hypotension. We used the GRADE approach to assess the quality of evidence.We extracted and analysed data regarding clinical outcomes that included mortality, bronchopulmonary dysplasia, death or bronchopulmonary dysplasia, failure to extubate, complications during primary hospitalisation, and long-term health outcomes. We included 32 RCTs enrolling a total of 4395 participants. The overall risk of bias of included studies was probably low, as all were RCTs, and most trials used rigorous methods. Investigators reported significant benefits for the following outcomes overall: lower rates of failure to extubate, decreased

Monoamine Oxidases Regulate Telencephalic Neural Progenitors in Late Embryonic and Early Postnatal Development

PubMed Central

Cheng, Aiwu; Scott, Anna L.; Ladenheim, Bruce; Chen, Kevin; Ouyang, Xin; Lathia, Justin D.; Mughal, Mohamed; Cadet, Jean Lud; Mattson, Mark P.; Shih, Jean C.

2010-01-01

Monoamine neurotransmitters play major roles in regulating a range of brain functions in adults and increasing evidence suggests roles for monoamines in brain development. Here we show that mice lacking the monoamine metabolic enzymes MAO A and MAO B (MAO AB-deficient mice) exhibit diminished proliferation of neural stem cells (NSC) in the developing telencephalon beginning in late gestation [embryonic day (E) 17.5], a deficit that persists in neonatal and adult mice. These mice showed significantly increased monoamine levels and anxiety-like behaviors as adults. Assessments of markers of intermediate progenitor cells (IPC) and mitosis showed that NSC in the subventricular zone (SVZ), but not in the ventricular zone, are reduced in MAO AB-deficient mice. A developmental time course of monoamines in frontal cortical tissues revealed increased serotonin levels as early as E14.5, and a further large increase was found between E17.5 and postnatal day 2. Administration of an inhibitor of serotonin synthesis (parachlorophenylalanine) between E14.5 and E19.5 restored the IPC numbers and SVZ thickness, suggesting the role of serotonin in the suppression of IPC proliferation. Studies of neurosphere cultures prepared from the telencephalon at different embryonic and postnatal ages showed that serotonin stimulates proliferation in wild-type, but not in MAO AB-deficient, NSC. Together, these results suggest that a MAO-dependent long-lasting alteration in the proliferation capacity of NSC occurs late in embryonic development and is mediated by serotonin. Our findings reveal novel roles for MAOs and serotonin in the regulation of IPC proliferation in the developing brain. PMID:20702706

Establishment of mammary gland model in vitro: culture and evaluation of a yak mammary epithelial cell line.

PubMed

Fu, Mei; Chen, Yabing; Xiong, Xianrong; Lan, Daoliang; Li, Jian

2014-01-01

This study aimed to establish yak mammary epithelial cells (YMECs) for an in vitro model of yak mammary gland biology. The primary culture of YMECs was obtained from mammary gland tissues of lactating yak and then characterized using immunocytochemistry, RT-PCR, and western blot analysis. Whether foreign genes could be transfected into the YMECs were examined by transfecting the EGFP gene into the cells. Finally, the effect of Staphylococcus aureus infection on YMECs was determined. The established YMECs retained the mammary epithelial cell characteristics. A spontaneously immortalized yak mammary epithelial cell line was established and could be continuously subcultured for more than 60 passages without senescence. The EGFP gene was successfully transferred into the YMECs, and the transfected cells could be maintained for a long duration in the culture by continuous subculturing. The cells expressed more antimicrobial peptides upon S.aureus invasion. Therefore, the established cell line could be considered a model system to understand yak mammary gland biology.

Postnatally acquired cytomegalovirus infection via breast milk: effects on hearing and development in preterm infants.

PubMed

Vollmer, Brigitte; Seibold-Weiger, Karin; Schmitz-Salue, Christine; Hamprecht, Klaus; Goelz, Rangmar; Krageloh-Mann, Ingeborg; Speer, Christian P

2004-04-01

In preterm infants there is a high risk of transmission of cytomegalovirus (CMV) via breast milk from seropositive mothers with reactivation of the virus during lactation. There is little information about the long term sequel of early postnatally acquired CMV infection in pre-term infants. This study aimed to investigate whether there was an increased frequency of impaired neurodevelopmental outcome and sensorineural hearing loss in preterm infants with postnatally acquired CMV infection through transmission by CMV-positive breast milk. Twenty-two preterm infants [median birth weight, 1020 g (range, 600 to 1870 g); median gestational age, 27.6 weeks (range, 23.6 to 32 weeks] with early postnatally acquired CMV infection by breast-feeding (onset of viruria between Days 23 and 190 postnatally) were compared with 22 CMV-negative preterm infants individually matched for gestational age, birth weight, gender, intracranial hemorrhage and duration of ventilation. At 2 to 4.5 years of age, follow-up assessments were conducted consisting of neurologic examination, neurodevelopmental assessment and detailed audiologic tests. None of the children had sensorineural hearing loss. There was no difference between the groups with regard to neurologic, speech and language or motor development. The results of this study suggest that early postnatally acquired CMV infection via CMV-positive breast milk does not have a negative effect on neurodevelopment and hearing in this group of patients. Because we studied a small number of infants, further follow-up studies are warranted in preterm infants with early postnatally acquired CMV infection.

EMMPRIN (basigin/CD147) expression is not correlated with MMP activity during adult mouse mammary gland development.

PubMed

Szymanowska, Malgorzata; Hendry, Kay A K; Robinson, Claire; Kolb, Andreas F

2009-01-01

Extracellular matrix metalloproteinase inducer (EMMPRIN/basigin/CD147) is a cell surface protein, which has been associated with the induction of matrix metalloproteinase (MMP) genes during cancer metastasis. EMMPRIN plays a role in a variety of physiological processes as is evident by the diverse deficiencies detectable in EMMPRIN knockout mice. We have analysed the role of EMMPRIN in the induction of MMP genes during mammary gland differentiation and involution. Co-transfection studies showed that EMMPRIN has diverse effects on MMP promoter activity in different mammary and non-mammary cell lines. Expression of EMMPRIN mRNA is enhanced markedly by insulin in a mammary gland cell line but appears to have no direct effect on MMP gene expression in these cells. Microarray analysis and quantitative PCR show that EMMPRIN is expressed throughout mammary gland differentiation in the mouse. Its expression decreases during early pregnancy and briefly after induction of mammary gland involution by litter removal. Immunohistochemical analysis shows that EMMPRIN expression is limited to the stromal compartment during pregnancy, whereas it is strongly expressed in the epithelium during lactation. In summary the data argue against a causal role for EMMPRIN for the induction of MMP gene expression during adult mammary gland development. These data therefore support a physiological role for EMMPRIN other than MMP induction in mammary gland biology. 2008 Wiley-Liss, Inc.

The effects of delivery route and anesthesia type on early postnatal weight loss in newborns: the role of vasoactive hormones.

PubMed

Okumus, Nurullah; Atalay, Yildiz; Onal, Eray E; Turkyilmaz, Canan; Senel, Saliha; Gunaydin, Berrin; Pasaoglu, Hatice; Koc, Esin; Ergenekon, Ebru; Unal, Suna

2011-01-01

To investigate the effects of delivery route and maternal anesthesia type and the roles of vasoactive hormones on early postnatal weight loss in term newborns. Ninety-four term infants delivered vaginally (group 1, n=31), cesarean section (C/S) with general anesthesia (GA) (group 2, n=29), and C/S with epidural anesthesia (EA) (group 3, n=34) were included in this study. All infants were weighed at birth and on the second day of life and intravenous (IV) fluid infused to the mothers for the last 6 h prior to delivery was recorded. Serum electrolytes, osmolality, N-terminal proANP (NT-proANP), brain natriuretic peptide (BNP), aldosterone and plasma antidiuretic hormone (ADH) concentrations were measured at cord blood and on the second day of life. Our research showed that postnatal weight loss of infants was higher in C/S than vaginal deliveries (5.7% vs. 1.3%) (p < 0.0001) and in EA group than GA group (6.8% vs. 4.3%) (p < 0.0001). Postnatal weight losses were correlated with IV fluid volume infused to the mothers for the last 6 h prior to delivery (R = 0.814, p = 0.000) and with serum NT-proANP (R = 0.418, p = 0.000), BNP (R = 0.454, p = 0.000), and ADH (R = 0.509, p = 0.000) but not with aldosterone concentrations (p > 0.05). Large amounts of IV fluid given to the mothers who were applied EA prior to the delivery affect their offsprings' postnatal weight loss via certain vasoactive hormones.

Understanding How Postnatal Depression Screening and Early Intervention Work in the Real World - A Singaporean Perspective.

PubMed

Lee, Theresa My; Bautista, Dianne; Chen, Helen Y

2016-10-01

Postnatal depression is a major public health problem with clearly established adverse effects in child outcomes. This study examines the 4-year outcomes of a screening and early intervention programme, in relation to improvement in symptoms, functioning and health quality of life. Women were prospectively recruited up to 6 months postdelivery, using the Edinburgh Postnatal Depression Scale (EPDS) as a screening tool. High-scorers (EPDS >13), were offered psychiatric consultation, and those with borderline scores (EPDS 10-12) were provided counselling, and offered follow-up phone counselling by the assigned case manager. Outcome measures were obtained at baseline, and at 6 months or discharge if earlier, for levels of symptoms, functioning, and health quality of life. From 2008 to 2012, 5245 women were screened, with 307 (5.9%) women with EPDS >13 receiving intervention. Of these, 70.0% had depression, 4.6% anxiety and 3.4% psychosis. In the depression subgroup, the net change was improvement of 93.4% EPDS symptom scores, 92.2% Global Assessment of Functioning (GAF) scores, and 88.3% visual analogue scale (EQ VAS) health quality of life scores. Outcome scores across diagnostic categories demonstrated median changes of 10 points on EPDS, 20 points on GAF, and 25 points on EQ VAS, reflecting 73.9%, 36.4% and 41.7% change from baseline scores. Women with psychosis showed the biggest (80.0%) relative change in GAF functioning scores from baseline to discharge but had the lowest median change in EPDS symptom scores. A screening and intervention programme rightly-sited within an obstetric setting can improve clinical outcomes because of early detection and intervention.

Postnatal Loss of Hap1 Reduces Hippocampal Neurogenesis and Causes Adult Depressive-Like Behavior in Mice

PubMed Central

Xiang, Jianxing; Yan, Sen; Li, Shi-Hua; Li, Xiao-Jiang

2015-01-01

Depression is a serious mental disorder that affects a person’s mood, thoughts, behavior, physical health, and life in general. Despite our continuous efforts to understand the disease, the etiology of depressive behavior remains perplexing. Recently, aberrant early life or postnatal neurogenesis has been linked to adult depressive behavior; however, genetic evidence for this is still lacking. Here we genetically depleted the expression of huntingtin-associated protein 1 (Hap1) in mice at various ages or in selective brain regions. Depletion of Hap1 in the early postnatal period, but not later life, led to a depressive-like phenotype when the mice reached adulthood. Deletion of Hap1 in adult mice rendered the mice more susceptible to stress-induced depressive-like behavior. Furthermore, early Hap1 depletion impaired postnatal neurogenesis in the dentate gyrus (DG) of the hippocampus and reduced the level of c-kit, a protein expressed in neuroproliferative zones of the rodent brain and that is stabilized by Hap1. Importantly, stereotaxically injected adeno-associated virus (AAV) that directs the expression of c-kit in the hippocampus promoted postnatal hippocampal neurogenesis and ameliorated the depressive-like phenotype in conditional Hap1 KO mice, indicating a link between postnatal-born hippocampal neurons and adult depression. Our results demonstrate critical roles for Hap1 and c-kit in postnatal neurogenesis and adult depressive behavior, and also suggest that genetic variations affecting postnatal neurogenesis may lead to adult depression. PMID:25875952

Postnatal loss of hap1 reduces hippocampal neurogenesis and causes adult depressive-like behavior in mice.

PubMed

Xiang, Jianxing; Yan, Sen; Li, Shi-Hua; Li, Xiao-Jiang

2015-04-01

Depression is a serious mental disorder that affects a person's mood, thoughts, behavior, physical health, and life in general. Despite our continuous efforts to understand the disease, the etiology of depressive behavior remains perplexing. Recently, aberrant early life or postnatal neurogenesis has been linked to adult depressive behavior; however, genetic evidence for this is still lacking. Here we genetically depleted the expression of huntingtin-associated protein 1 (Hap1) in mice at various ages or in selective brain regions. Depletion of Hap1 in the early postnatal period, but not later life, led to a depressive-like phenotype when the mice reached adulthood. Deletion of Hap1 in adult mice rendered the mice more susceptible to stress-induced depressive-like behavior. Furthermore, early Hap1 depletion impaired postnatal neurogenesis in the dentate gyrus (DG) of the hippocampus and reduced the level of c-kit, a protein expressed in neuroproliferative zones of the rodent brain and that is stabilized by Hap1. Importantly, stereotaxically injected adeno-associated virus (AAV) that directs the expression of c-kit in the hippocampus promoted postnatal hippocampal neurogenesis and ameliorated the depressive-like phenotype in conditional Hap1 KO mice, indicating a link between postnatal-born hippocampal neurons and adult depression. Our results demonstrate critical roles for Hap1 and c-kit in postnatal neurogenesis and adult depressive behavior, and also suggest that genetic variations affecting postnatal neurogenesis may lead to adult depression.

Prenatal Exposure to Unconventional Oil and Gas Operation Chemical Mixtures Altered Mammary Gland Development in Adult Female Mice.

PubMed

Sapouckey, Sarah A; Kassotis, Christopher D; Nagel, Susan C; Vandenberg, Laura N

2018-03-01

Unconventional oil and gas (UOG) operations, which combine hydraulic fracturing (fracking) and directional drilling, involve the use of hundreds of chemicals, including many with endocrine-disrupting properties. Two previous studies examined mice exposed during early development to a 23-chemical mixture of UOG compounds (UOG-MIX) commonly used or produced in the process. Both male and female offspring exposed prenatally to one or more doses of UOG-MIX displayed alterations to endocrine organ function and serum hormone concentrations. We hypothesized that prenatal UOG-MIX exposure would similarly disrupt development of the mouse mammary gland. Female C57Bl/6 mice were exposed to ~3, ~30, ~ 300, or ~3000 μg/kg/d UOG-MIX from gestational day 11 to birth. Although no effects were observed on the mammary glands of these females before puberty, in early adulthood, females exposed to 300 or 3000 μg/kg/d UOG-MIX developed more dense mammary epithelial ducts; females exposed to 3 μg/kg/d UOG-MIX had an altered ratio of apoptosis to proliferation in the mammary epithelium. Furthermore, adult females from all UOG-MIX-treated groups developed intraductal hyperplasia that resembled terminal end buds (i.e., highly proliferative structures typically seen at puberty). These results suggest that the mammary gland is sensitive to mixtures of chemicals used in UOG production at exposure levels that are environmentally relevant. The effect of these findings on the long-term health of the mammary gland, including its lactational capacity and its risk of cancer, should be evaluated in future studies. Copyright © 2018 Endocrine Society.

Methylxanthines during pregnancy and early postnatal life.

PubMed

Adén, Ulrika

2011-01-01

World-wide, many fetuses and infants are exposed to methylxanthines via maternal consumption of coffee and other beverages containing these substances. Methylxanthines (caffeine, theophylline and aminophylline) are also commonly used as a medication for apnea of prematurity.The metabolism of methylxanthines is impaired in pregnant women, fetuses and neonates, leading to accumulating levels thereof. Methylxanthines readily passes the placenta barrier and enters all tissues and thus may affect the fetus/newborn at any time during pregnancy or postnatal life, given that the effector systems are mature.At clinically relevant doses, the major effector system for methylxanthines is adenosine receptors. Animal studies suggest that adenosine receptors in the cardiovascular, respiratory and immune system are developed at birth, but that cerebral adenosine receptors are not fully functional. Furthermore animal studies have shown protective positive effects of methylxanthines in situations of hypoxia/ischemia in neonates. Similarly, a positive long-term effect on lung function and CNS development was found in human preterm infants treated with high doses of caffeine for apneas. There is now evidence that the overall benefits from methylxanthine therapy for apnea of prematurity outweigh potential short-term risks.On the other hand it is important to note that experimental studies have indicated that long-term effects of caffeine during pregnancy and postnatally may include altered behavior and altered respiratory control in the offspring, although there is currently no human data to support this.Some epidemiology studies have reported negative effects on pregnancy and perinatal outcomes related to maternal ingestion of high doses of caffeine, but the results are inconclusive. The evidence base for adverse effects of caffeine in first third of pregnancy are stronger than for later parts of pregnancy and there is currently insufficient evidence to advise women to restrict

Endovascular repair of an internal mammary artery aneurysm in a patient with SMAD-3 mutation.

PubMed

Burke, Chris; Shalhub, Sherene; Starnes, Benjamin W

2015-08-01

Aneurysms of the internal mammary artery are rare. We describe a case of a 49-year-old woman with a SMAD3 mutation who presented with left internal mammary artery aneurysm that was thought to have ruptured, causing a large spontaneous left mediastinal hematoma. The aneurysm was treated successfully months after initial presentation with coil embolization. SMAD3 mutations are linked to familial thoracic aortic aneurysms and dissections, peripheral aneurysms, and early-onset osteoarthritis, with an estimated incidence of 2% in families with familial thoracic aortic aneurysms and dissections. To our knowledge, this is the first case in the literature to link a SMAD3 mutation with internal mammary artery aneurysm. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Long-Term Impacts of Foetal Malnutrition Followed by Early Postnatal Obesity on Fat Distribution Pattern and Metabolic Adaptability in Adult Sheep

PubMed Central

Khanal, Prabhat; Johnsen, Lærke; Axel, Anne Marie Dixen; Hansen, Pernille Willert; Kongsted, Anna Hauntoft; Lyckegaard, Nette Brinch; Nielsen, Mette Olaf

2016-01-01

We aimed to investigate whether over- versus undernutrition in late foetal life combined with obesity development in early postnatal life have differential implications for fat distribution and metabolic adaptability in adulthood. Twin-pregnant ewes were fed NORM (100% of daily energy and protein requirements), LOW (50% of NORM) or HIGH (150%/110% of energy/protein requirements) diets during the last trimester. Postnatally, twin-lambs received obesogenic (HCHF) or moderate (CONV) diets until 6 months of age, and a moderate (obesity correcting) diet thereafter. At 2½ years of age (adulthood), plasma metabolite profiles during fasting, glucose, insulin and propionate (in fed and fasted states) tolerance tests were examined. Organ weights were determined at autopsy. Early obesity development was associated with lack of expansion of perirenal, but not other adipose tissues from adolescence to adulthood, resulting in 10% unit increased proportion of mesenteric of intra-abdominal fat. Prenatal undernutrition had a similar but much less pronounced effect. Across tolerance tests, LOW-HCHF sheep had highest plasma levels of cholesterol, urea-nitrogen, creatinine, and lactate. Sex specific differences were observed, particularly with respect to fat deposition, but direction of responses to early nutrition impacts were similar. However, prenatal undernutrition induced greater metabolic alterations in adult females than males. Foetal undernutrition, but not overnutrition, predisposed for adult hypercholesterolaemia, hyperureaemia, hypercreatinaemia and hyperlactataemia, which became manifested only in combination with early obesity development. Perirenal expandability may play a special role in this context. Differential nutrition recommendations may be advisable for individuals with low versus high birth weights. PMID:27257993

Impact of Early Postnatal Androgen Exposure on Voice Development

PubMed Central

Grisa, Leila; Leonel, Maria L.; Gonçalves, Maria I. R.; Pletsch, Francisco; Sade, Elis R.; Custódio, Gislaine; Zagonel, Ivete P. S.; Longui, Carlos A.; Figueiredo, Bonald C.

2012-01-01

Background The impact of early postnatal androgen exposure on female laryngeal tissue may depend on certain characteristics of this exposure. We assessed the impact of the dose, duration, and timing of early androgen exposure on the vocal development of female subjects who had been treated for adrenocortical tumor (ACT) in childhood. Methods The long-term effects of androgen exposure on the fundamental vocal frequency (F0), vocal pitch, and final height and the presence of virilizing signs were examined in 9 adult (age, 18.4 to 33.5 years) and 10 adolescent (13.6 to 17.8 years) female ACT patients. We also compared the current values with values obtained 0.9 years to 7.4 years after these subjects had undergone ACT surgery, a period during which they had shown normal androgen levels. Results Of the 19 subjects, 17 (89%) had been diagnosed with ACT before 4 years of age, 1 (5%) at 8.16 years, and 1 (5%) at 10.75 years. Androgen exposure (2 to 30 months) was sufficiently strong to cause pubic hair growth in all subjects and clitoromegaly in 74% (14/19) of the subjects, but did not reduce their height from the target value. Although androgen exposure induced a remarkable reduction in F0 (132 Hz) and moderate pitch virilization in 1 subject and partial F0 virilization, resulting in F0 of 165 and 169 Hz, in 2 subjects, the majority had normal F0 ranging from 189 to 245 Hz. Conclusions Female laryngeal tissue is less sensitive to androgen exposure between birth and adrenarche than during other periods. Differential larynx sensitivity to androgen exposure in childhood and F0 irreversibility in adulthood are age-, concentration-, duration-, and timing-dependent events that may also be affected by exposure to inhibitory or stimulatory hormones. Further studies are required to better characterize each of these factors. PMID:23284635

Influence of prenatal and postnatal growth on intellectual functioning in school-aged children.

PubMed

Pongcharoen, Tippawan; Ramakrishnan, Usha; DiGirolamo, Ann M; Winichagoon, Pattanee; Flores, Rafael; Singkhornard, Jintana; Martorell, Reynaldo

2012-05-01

To assess the relative influence of size at birth, infant growth, and late postnatal growth on intellectual functioning at 9 years of age. A follow-up, cross-sectional study. Three districts in Khon Kaen province, northeast Thailand. A total of 560 children, or 92% of former participants of a trial of iron and/or zinc supplementation during infancy. Prenatal (size at birth), early infancy (birth to 4 months), late infancy (4 months to 1 year), and late postnatal (1 to 9 years) growth. Multiple-stage least squares analyses were used to generate uncorrelated residuals of postnatal growth. Intellectual functioning was measured at 9 years using the Wechsler Intelligence Scale for Children and the Raven's Colored Progressive Matrices (Pearson). Analyses included adjustment for maternal, household, and school characteristics. Significant relationships were found between growth and IQ (Wechsler Intelligence Scale for children, third edition, Thai version), but only up to 1 year of age; overall, growth was not related to the Raven's Colored Progressive Matrices. The strongest and most consistent relationships were with length (birth, early infancy, and late infancy); for weight, only early infancy gain was consistently related to IQ. Head circumference at birth was not collected routinely; head circumference at 4 months (but not head circumference growth thereafter) was related to IQ. Late postnatal growth was not associated with any outcome. Physical growth in early infancy (and, to a lesser extent, physical growth in late infancy and at birth) is associated with IQ at 9 years of age. Early infancy may be a critical window for human development.

Cripto-1 Ablation Disrupts Alveolar Development in the Mouse Mammary Gland through a Progesterone Receptor–Mediated Pathway

PubMed Central

Klauzinska, Malgorzata; McCurdy, David; Rangel, Maria Cristina; Vaidyanath, Arun; Castro, Nadia P.; Shen, Michael M.; Gonzales, Monica; Bertolette, Daniel; Bianco, Caterina; Callahan, Robert; Salomon, David S.; Raafat, Ahmed

2016-01-01

Cripto-1, a member of the epidermal growth factor–Cripto-1/FRL-1/Cryptic family, is critical for early embryonic development. Together with its ligand Nodal, Cripto-1 has been found to be associated with the undifferentiated status of mouse and human embryonic stem cells. Several studies have clearly shown that Cripto-1 is involved in regulating branching morphogenesis and epithelial-mesenchymal transition of the mammary gland both in vitro and in vivo and together with the cofactor GRP78 is critical for the maintenance of mammary stem cells ex vivo. Our previous studies showed that mammary-specific overexpression of human Cripto-1 exhibited dramatic morphological alterations in nulliparous mice mammary glands. The present study shows a novel mechanism for Cripto-1 regulation of mammary gland development through direct effects on progesterone receptor expression and pathways regulated by progesterone in the mammary gland. We demonstrate a strict temporal regulation of mouse Cripto-1 (mCripto-1) expression that occurs during mammary gland development and a stage-specific function of mCripto-1 signaling during mammary gland development. Our data suggest that Cripto-1, like the progesterone receptor, is not required for the initial ductal growth but is essential for subsequent side branching and alveologenesis during the initial stages of pregnancy. Dissection of the mechanism by which this occurs indicates that mCripto-1 activates receptor activator NF-κB/receptor activator NF-κB ligand, and NF-κB signaling pathways. PMID:26429739

Notch Signaling in Postnatal Pituitary Expansion: Proliferation, Progenitors, and Cell Specification

PubMed Central

Nantie, Leah B.; Himes, Ashley D.; Getz, Dan R.

2014-01-01

Mutations in PROP1 account for up to half of the cases of combined pituitary hormone deficiency that result from known causes. Despite this, few signaling molecules and pathways that influence PROP1 expression have been identified. Notch signaling has been linked to Prop1 expression, but the developmental periods during which Notch signaling influences Prop1 and overall pituitary development remain unclear. To test the requirement for Notch signaling in establishing the normal pituitary hormone milieu, we generated mice with early embryonic conditional loss of Notch2 (conditional knockout) and examined the consequences of chemical Notch inhibition during early postnatal pituitary maturation. We show that loss of Notch2 has little influence on early embryonic pituitary proliferation but is crucial for postnatal progenitor maintenance and proliferation. In addition, we show that Notch signaling is necessary embryonically and postnatally for Prop1 expression and robust Pit1 lineage hormone cell expansion, as well as repression of the corticotrope lineage. Taken together, our studies identify temporal and cell type–specific roles for Notch signaling and highlight the importance of this pathway throughout pituitary development. PMID:24673559

Pim-1 kinase expression during murine mammary development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gapter, Leslie A.; School of Molecular Biosciences, Washington State University, Pullman, WA 99164-4234; Magnuson, Nancy S.

2006-07-07

Pim-1 kinase phosphorylates substrates whose activities are linked to proliferation, survival, differentiation, and apoptosis. Although pim-1 is induced by hormones and cytokines, the hormonal control and contribution of Pim-1 to mammary gland development have not been evaluated. We examined Pim-1 expression in mammary cell lines, investigated whether Pim-1 levels could be altered in breast epithelia by mammogenic hormones, and evaluated Pim-1 expression during mammary development. We found that Pim-1 was elevated in most mammary carcinoma cell lines and progesterone increased Pim-1 protein to some extent in non-tumorigenic mammary epithelia. Pim-1 expression in situ was consistent with the documented profile ofmore » progesterone activity in mouse mammary glands. Pim-1 nuclear localization correlated with cytoplasmic distribution for its substrate, p21{sup CIP/Waf1}, and we found that Pim-1 and p21 associate in vitro. Our results suggest that Pim-1 expression may be regulated by progesterone during mammary development and Pim-1 associates with p21 in mammary epithelial cells.« less

Early postnatal effects of noopept and piracetam on declarative and procedural memory of adult male and female rats.

PubMed

Trofimov, S S; Voronina, T A; Guzevatykh, L S

2005-06-01

We studied the effect of a new nootropic dipeptide Noopept and reference nootropic preparation piracetam injected subcutaneously on days 8-20 of life on learning of alternative feeding response in a 6-arm-maze in male and female rats. Early postnatal administration of Noopept disturbed the dynamics of learning by parameters of declarative and procedural memory. Piracetam impaired learning by parameters of procedural, but not declarative memory (only in males). Both preparations decreased the ratio of successfully learned males (but not females). The observed effects were not associated with changes in locomotor activity.

Fetal Nicotine Exposure Increases Preference for Nicotine Odor in Early Postnatal and Adolescent, but Not Adult, Rats

PubMed Central

Mantella, Nicole M.; Kent, Paul F.; Youngentob, Steven L.

2013-01-01

Human studies demonstrate a four-fold increased possibility of smoking in the children of mothers who smoked during pregnancy. Nicotine is the active addictive component in tobacco-related products, crossing the placenta and contaminating the amniotic fluid. It is known that chemosensory experience in the womb can influence postnatal odor-guided preference behaviors for an exposure stimulus. By means of behavioral and neurophysiologic approaches, we examined whether fetal nicotine exposure, using mini-osmotic pumps, altered the response to nicotine odor in early postnatal (P17), adolescent (P35) and adult (P90) progeny. Compared with controls, fetal exposed rats displayed an altered innate response to nicotine odor that was evident at P17, declined in magnitude by P35 and was absent at P90 - these effects were specific to nicotine odor. The behavioral effect in P17 rats occurred in conjunction with a tuned olfactory mucosal response to nicotine odor along with an untoward consequence on the epithelial response to other stimuli – these P17 neural effects were absent in P35 and P90 animals. The absence of an altered neural effect at P35 suggests that central mechanisms, such as nicotine-induced modifications of the olfactory bulb, bring about the altered behavioral response to nicotine odor. Together, these findings provide insights into how fetal nicotine exposure influences the behavioral preference and responsiveness to the drug later in life. Moreover, they add to a growing literature demonstrating chemosensory mechanisms by which patterns of maternal drug use can be conveyed to offspring, thereby enhancing postnatal vulnerability for subsequent use and abuse. PMID:24358374

Social isolation induces autophagy in the mouse mammary gland: link to increased mammary cancer risk

PubMed Central

Sumis, Allison; Cook, Katherine L; Andrade, Fabia O; Hu, Rong; Kidney, Emma; Zhang, Xiyuan; Kim, Dominic; Carney, Elissa; Nguyen, Nguyen; Yu, Wei; Bouker, Kerrie B; Cruz, Idalia; Clarke, Robert; Hilakivi-Clarke, Leena

2018-01-01

Social isolation is a strong predictor of early all-cause mortality and consistently increases breast cancer risk in both women and animal models. Because social isolation increases body weight, we compared its effects to those caused by a consumption of obesity-inducing diet (OID) in C57BL/6 mice. Social isolation and OID impaired insulin and glucose sensitivity. In socially isolated, OID-fed mice (I-OID), insulin resistance was linked to reduced Pparg expression and increased neuropeptide Y levels, but in group-housed OID fed mice (G-OID), it was linked to increased leptin and reduced adiponectin levels, indicating that the pathways leading to insulin resistance are different. Carcinogen-induced mammary tumorigenesis was significantly higher in I-OID mice than in the other groups, but cancer risk was also increased in socially isolated, control diet-fed mice (I-C) and G-OID mice compared with that in controls. Unfolded protein response (UPR) signaling (GRP78; IRE1) was upregulated in the mammary glands of OID-fed mice, but not in control diet-fed, socially isolated I-C mice. In contrast, expression of BECLIN1, ATG7 and LC3II were increased, and p62 was downregulated by social isolation, indicating increased autophagy. In the mammary glands of socially isolated mice, but not in G-OID mice, mRNA expressions of p53 and the p53-regulated autophagy inducer Dram1 were upregulated, and nuclear p53 staining was strong. Our findings further indicated that autophagy and tumorigenesis were not increased in Atg7+/− mice kept in social isolation and fed OID. Thus, social isolation may increase breast cancer risk by inducing autophagy, independent of changes in body weight. PMID:27550962

Social isolation induces autophagy in the mouse mammary gland: link to increased mammary cancer risk.

PubMed

Sumis, Allison; Cook, Katherine L; Andrade, Fabia O; Hu, Rong; Kidney, Emma; Zhang, Xiyuan; Kim, Dominic; Carney, Elissa; Nguyen, Nguyen; Yu, Wei; Bouker, Kerrie B; Cruz, Idalia; Clarke, Robert; Hilakivi-Clarke, Leena

2016-10-01

Social isolation is a strong predictor of early all-cause mortality and consistently increases breast cancer risk in both women and animal models. Because social isolation increases body weight, we compared its effects to those caused by a consumption of obesity-inducing diet (OID) in C57BL/6 mice. Social isolation and OID impaired insulin and glucose sensitivity. In socially isolated, OID-fed mice (I-OID), insulin resistance was linked to reduced Pparg expression and increased neuropeptide Y levels, but in group-housed OID fed mice (G-OID), it was linked to increased leptin and reduced adiponectin levels, indicating that the pathways leading to insulin resistance are different. Carcinogen-induced mammary tumorigenesis was significantly higher in I-OID mice than in the other groups, but cancer risk was also increased in socially isolated, control diet-fed mice (I-C) and G-OID mice compared with that in controls. Unfolded protein response (UPR) signaling (GRP78; IRE1) was upregulated in the mammary glands of OID-fed mice, but not in control diet-fed, socially isolated I-C mice. In contrast, expression of BECLIN1, ATG7 and LC3II were increased, and p62 was downregulated by social isolation, indicating increased autophagy. In the mammary glands of socially isolated mice, but not in G-OID mice, mRNA expressions of p53 and the p53-regulated autophagy inducer Dram1 were upregulated, and nuclear p53 staining was strong. Our findings further indicated that autophagy and tumorigenesis were not increased in Atg7(+/-) mice kept in social isolation and fed OID. Thus, social isolation may increase breast cancer risk by inducing autophagy, independent of changes in body weight. © 2016 Society for Endocrinology.

Synergistic effects of androgen and estrogen on the mouse uterus and mammary gland.

PubMed

Zhang, Jian; Sun, Yibin; Liu, Yunhai; Sun, Yi; Liao, Dezhong Joshua

2004-10-01

Many studies have suggested that elevated estrogens and androgens may be etiologically related to the development of breast cancer, endometrial cancer and uterine leiomyomas. We and other investigators have previously shown that estrogen and androgen are synergistic in the induction of mammary carcinogenesis in the Noble rat. However, the mechanisms behind the synergy is unknown, and it is unclear whether such synergy is unique for the Noble rat and for the mammary gland. In this study we treated female FVB mice with 17beta-estradiol (E2) and 5alpha-dihydrotestosterone-bezonate (DHT-B), alone and in combination, using silastic tubing for 2-7 months. The results showed that DHT-B alone induced proliferation of uterine endometrial epithelium and myometrial smooth muscle cells, whereas E2 alone induced much more pronounced growth of endometrial epithelium without affecting smooth muscle cells. Combined treatment with E2+DHT-B caused an even more severe hyperplasia of endometrial epithelium and myometrial muscle cells, compared with the treatment with each hormone alone. Uterine leiomyomas were observed in 2 of 6 mice at 7 months of combined treatment but not in any of 6 or 7 mice receiving each single hormone. DHT-B alone induced growth and secretion of mammary ductal cells, as well as growth of mammary stroma. E2 alone stimulated much more pronounced growth of both ductal cells and alveolar cells and secretion of alveolar cells, but had no effect on mammary stroma. Treatment with both E2 and DHT-B caused more severe hyperplasia of mammary ducts and alveoli, compared to the treatment with each hormone alone. Intraductal hyperplasia occurred early and frequently in the E2+DHT-B- treated mice, but no mammary tumors were observed. These results suggest that E2 and DHT-B have synergistic effects on the growth of uterine endometrial epithelium and myometrial muscle cells, as well as mammary epithelial ducts and alveoli.

Early postnatal development of vasoactive intestinal polypeptide- and peptide histidine isoleucine-immunoreactive structures in the cat visual cortex.

PubMed

Wahle, P; Meyer, G

1989-04-08

The early postnatal development of neurons containing vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) has been analyzed in visual areas 17 and 18 of cats aged from postnatal day (P) 0 to adulthood. Neuronal types are established mainly by axonal criteria. Both peptides occur in the same neuronal types and display the same postnatal chronology of appearance. Several cell types are transient, which means that they are present in the cortex only for a limited period of development. According to their chronology of appearance the VIP/PHI-immunoreactive (ir) cell types are grouped into three neuronal populations. The first population comprises six cell types which appear early in postnatal life. The pseudohorsetail cells of layer I possess a vertically descending axon which initially gives rise to recurrent collaterals, then forms a bundle passing layers III to V, and finally, horizontal terminal fibers in layer VI. The neurons differentiate at P 4 and disappear by degeneration around P 30. The neurons with columnar dendritic fields of layers IV/V are characterized by a vertical arrangement of long dendrites ascending or descending parallel to each other, thus forming an up to 600 microns long dendritic column. Their axons always descend and terminate in broad fields in layer VI. The neurons appear at P 7 and are present until P 20. The multipolar neurons of layer VI occur in isolated positions and have broad axonal territories. The neurons differentiate at P 7 and persist into adulthood. Bitufted to multipolar neurons of layers II/III have axons descending as a single fiber to layer VI, where they terminate. The neurons appear at P 12 and persist into adulthood. The four cell types described above issue a vertically oriented fiber architecture in layers II-V and a horizontal terminal plexus in layer VI which is dense during the second, third and fourth week. Concurrent with the disappearance of the two transient types the number of

Mammary and extramammary Paget's disease

PubMed Central

Lloyd, J; Flanagan, A

2000-01-01

Mammary and extramammary Paget's disease are uncommon intraepithelial adenocarcinomas. Both conditions have similar clinical features, which mimic inflammatory and infective diseases. Histological diagnostic confusion can arise between Paget's disease and other neoplastic conditions affecting the skin, with the most common differential diagnoses being malignant melanoma and atypical squamous disease. The glandular differentiation of both mammary Paget's disease and extramammary Paget's disease is indicated by morphological appearances, the presence of intracellular mucin in many cases, and positive immunohistochemical staining for glandular cytokeratins, epithelial membrane antigen, and carcinoembryonic antigen. This article provides an overview of mammary and extramammary Paget's disease and discusses recent evidence regarding the cell of origin. The concepts of primary and secondary Paget's disease are presented and the differential diagnosis is discussed with reference to immunohistochemical markers that might be of diagnostic value. Key Words: mammary Paget's disease • extramammary Paget's disease PMID:11064666

[Postnatal diagnosis of gastric volvulus revealing congenital diaphragmatic hernia].

PubMed

Aprahamian, A; Nouyrigat, V; Grévent, D; Hervieux, E; Chéron, G

2017-05-01

Postnatally diagnosed congenital diaphragmatic hernias (CDH) are rare and have a better prognosis than those diagnosed prenatally. Postnatal symptoms can be respiratory, digestive, or mixed. Gastric volvulus can reveal CDH. Symptoms are pain, abdominal distension, and/or vomiting. Upper gastrointestinal barium X-ray radiography provides the diagnosis. Prognosis is related to early surgical management in complicated forms with intestinal occlusion or sub-occlusion. We report on an infant who presented with vomiting, which revealed gastric volvulus associated with a CDH. Progression was favorable after surgical treatment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effects of short-duration electromagnetic radiation on early postnatal neurogenesis in rats: Fos and NADPH-d histochemical studies.

PubMed

Orendáčová, Judita; Orendáč, Martin; Mojžiš, Miroslav; Labun, Ján; Martončíková, Marcela; Saganová, Kamila; Lievajová, Kamila; Blaško, Juraj; Abdiová, Henrieta; Gálik, Ján; Račeková, Eniko

2011-11-01

The immediate effects of whole body electromagnetic radiation (EMR) were used to study postnatal neurogenesis in the subventricular zone (SVZ) and rostral migratory stream (RMS) of Wistar rats of both sexes. Newborn postnatal day 7 (P7) and young adult rats (P28) were exposed to pulsed electromagnetic fields (EMF) at a frequency of 2.45 GHz and mean power density of 2.8 mW/cm(2) for 2 h. Post-irradiation changes were studied using immunohistochemical localization of Fos and NADPH-d. We found that short-duration exposure induces increased Fos immunoreactivity selectively in cells of the SVZ of P7 and P28 rats. There were no Fos positive cells visible within the RMS of irradiated rats. These findings indicate that some differences exist in prerequisites of proliferating cells between the SVZ and RMS regardless of the age of the rats. Short-duration exposure also caused praecox maturation of NADPH-d positive cells within the RMS of P7 rats. The NADPH-d positive cells appeared several days earlier than in age-matched controls, and their number and morphology showed characteristics of adult rats. On the other hand, in the young adult P28 rats, EMR induced morphological signs typical of early postnatal age. These findings indicate that EMR causes age-related changes in the production of nitric oxide (NO), which may lead to different courses of the proliferation cascade in newborn and young adult neurogenesis. Copyright © 2010 Elsevier GmbH. All rights reserved.

Prostate and mammary adenocarcinoma in transgenic mice carrying a rat C3(1) simian virus 40 large tumor antigen fusion gene.

PubMed Central

Maroulakou, I G; Anver, M; Garrett, L; Green, J E

1994-01-01

A transgenic mouse model for prostate and mammary cancer has been developed in mice containing a recombinant gene expressing the simian virus 40 early-region transforming sequences under the regulatory control of the rat prostatic steroid binding protein [C3(1)] gene. Male transgenic mice develop prostatic hyperplasia in early life that progresses to adenoma or adenocarcinoma in most animals surviving to longer than 7 months of age. Prostate cancer metastases to lung have been observed. Female animals from the same founder lines generally develop mammary hyperplasia by 3 months of age with subsequent development of mammary adenocarcinoma by 6 months of age in 100% of the animals. The development of tumors correlates with the expression of the transgene as determined by Northern blot and immunohistochemical analyses. The results of these experiments demonstrate that the C3(1) regulatory region used in these experiments is useful for targeting expression to the prostate and mammary gland. To our knowledge, this experimental system is the first reported transgenic mouse model for prostate cancer. These transgenic animals offer the opportunity to study hormone response elements in vivo and the multistage progression from normal tissue to carcinoma in the prostate and mammary glands. Images PMID:7972041

A mammary cell-specific enhancer in mouse mammary tumor virus DNA is composed of multiple regulatory elements including binding sites for CTF/NFI and a novel transcription factor, mammary cell-activating factor.

PubMed Central

Mink, S; Härtig, E; Jennewein, P; Doppler, W; Cato, A C

1992-01-01

Mouse mammary tumor virus (MMTV) is a milk-transmitted retrovirus involved in the neoplastic transformation of mouse mammary gland cells. The expression of this virus is regulated by mammary cell type-specific factors, steroid hormones, and polypeptide growth factors. Sequences for mammary cell-specific expression are located in an enhancer element in the extreme 5' end of the long terminal repeat region of this virus. This enhancer, when cloned in front of the herpes simplex thymidine kinase promoter, endows the promoter with mammary cell-specific response. Using functional and DNA-protein-binding studies with constructs mutated in the MMTV long terminal repeat enhancer, we have identified two main regulatory elements necessary for the mammary cell-specific response. These elements consist of binding sites for a transcription factor in the family of CTF/NFI proteins and the transcription factor mammary cell-activating factor (MAF) that recognizes the sequence G Pu Pu G C/G A A G G/T. Combinations of CTF/NFI- and MAF-binding sites or multiple copies of either one of these binding sites but not solitary binding sites mediate mammary cell-specific expression. The functional activities of these two regulatory elements are enhanced by another factor that binds to the core sequence ACAAAG. Interdigitated binding sites for CTF/NFI, MAF, and/or the ACAAAG factor are also found in the 5' upstream regions of genes encoding whey milk proteins from different species. These findings suggest that mammary cell-specific regulation is achieved by a concerted action of factors binding to multiple regulatory sites. Images PMID:1328867

Pre- and Post-Natal Maternal Depressive Symptoms in Relation with Infant Frontal Function, Connectivity, and Behaviors

PubMed Central

Soe, Ni Ni; Wen, Daniel J.; Poh, Joann S.; Li, Yue; Broekman, Birit F. P.; Chen, Helen; Chong, Yap Seng; Kwek, Kenneth; Saw, Seang-Mei; Gluckman, Peter D.; Meaney, Michael J.; Rifkin-Graboi, Anne; Qiu, Anqi

2016-01-01

This study investigated the relationships between pre- and early post-natal maternal depression and their changes with frontal electroencephalogram (EEG) activity and functional connectivity in 6- and 18-month olds, as well as externalizing and internalizing behaviors in 24-month olds (n = 258). Neither prenatal nor postnatal maternal depressive symptoms independently predicted neither the frontal EEG activity nor functional connectivity in 6- and 18-month infants. However, increasing maternal depressive symptoms from the prenatal to postnatal period predicted greater right frontal activity and relative right frontal asymmetry amongst 6-month infants but these finding were not observed amongst 18-month infants after adjusted for post-conceptual age on the EEG visit day. Subsequently increasing maternal depressive symptoms from the prenatal to postnatal period predicted lower right frontal connectivity within 18-month infants but not among 6-month infants after controlling for post-conceptual age on the EEG visit day. These findings were observed in the full sample and the female sample but not in the male sample. Moreover, both prenatal and early postnatal maternal depressive symptoms independently predicted children’s externalizing and internalizing behaviors at 24 months of age. This suggests that the altered frontal functional connectivity in infants born to mothers whose depressive symptomatology increases in the early postnatal period compared to that during pregnancy may reflect a neural basis for the familial transmission of phenotypes associated with mood disorders, particularly in girls. PMID:27073881

Left-right analysis of mammary gland development in retinoid X receptor-α+/- mice.

PubMed

Robichaux, Jacqulyne P; Fuseler, John W; Patel, Shrusti S; Kubalak, Steven W; Hartstone-Rose, Adam; Ramsdell, Ann F

2016-12-19

Left-right (L-R) differences in mammographic parenchymal patterns are an early predictor of breast cancer risk; however, the basis for this asymmetry is unknown. Here, we use retinoid X receptor alpha heterozygous null (RXRα +/- ) mice to propose a developmental origin: perturbation of coordinated anterior-posterior (A-P) and L-R axial body patterning. We hypothesized that by analogy to somitogenesis-in which retinoic acid (RA) attenuation causes anterior somite pairs to develop L-R asynchronously-that RA pathway perturbation would likewise result in asymmetric mammary development. To test this, mammary glands of RXRα +/- mice were quantitatively assessed to compare left- versus right-side ductal epithelial networks. Unlike wild-type controls, half of the RXRα +/- thoracic mammary gland (TMG) pairs exhibited significant L-R asymmetry, with left-side reduction in network size. In RXRα +/- TMGs in which symmetry was maintained, networks had bilaterally increased size, with left networks showing greater variability in area and pattern. Reminiscent of posterior somites, whose bilateral symmetry is refractory to RA attenuation, inguinal mammary glands (IMGs) also had bilaterally increased network size, but no loss of symmetry. Together, these results demonstrate that mammary glands exhibit differential A-P sensitivity to RXRα heterozygosity, with ductal network symmetry markedly compromised in anterior but not posterior glands. As TMGs more closely model human breast development than IMGs, these findings raise the possibility that for some women, breast cancer risk may initiate with subtle axial patterning defects that result in L-R asymmetric growth and pattern of the mammary ductal epithelium.This article is part of the themed issue 'Provocative questions in left-right asymmetry'. © 2016 The Author(s).

Cripto-1 ablation disrupts alveolar development in the mouse mammary gland through a progesterone receptor-mediated pathway.

PubMed

Klauzinska, Malgorzata; McCurdy, David; Rangel, Maria Cristina; Vaidyanath, Arun; Castro, Nadia P; Shen, Michael M; Gonzales, Monica; Bertolette, Daniel; Bianco, Caterina; Callahan, Robert; Salomon, David S; Raafat, Ahmed

2015-11-01

Cripto-1, a member of the epidermal growth factor-Cripto-1/FRL-1/Cryptic family, is critical for early embryonic development. Together with its ligand Nodal, Cripto-1 has been found to be associated with the undifferentiated status of mouse and human embryonic stem cells. Several studies have clearly shown that Cripto-1 is involved in regulating branching morphogenesis and epithelial-mesenchymal transition of the mammary gland both in vitro and in vivo and together with the cofactor GRP78 is critical for the maintenance of mammary stem cells ex vivo. Our previous studies showed that mammary-specific overexpression of human Cripto-1 exhibited dramatic morphological alterations in nulliparous mice mammary glands. The present study shows a novel mechanism for Cripto-1 regulation of mammary gland development through direct effects on progesterone receptor expression and pathways regulated by progesterone in the mammary gland. We demonstrate a strict temporal regulation of mouse Cripto-1 (mCripto-1) expression that occurs during mammary gland development and a stage-specific function of mCripto-1 signaling during mammary gland development. Our data suggest that Cripto-1, like the progesterone receptor, is not required for the initial ductal growth but is essential for subsequent side branching and alveologenesis during the initial stages of pregnancy. Dissection of the mechanism by which this occurs indicates that mCripto-1 activates receptor activator NF-κB/receptor activator NF-κB ligand, and NF-κB signaling pathways. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Effect of prenatal and postnatal malnutrition on intellectual functioning in early school-aged children in rural western China

PubMed Central

Li, Chao; Zhu, Ni; Zeng, Lingxia; Dang, Shaonong; Zhou, Jing; Yan, Hong

2016-01-01

Abstract The aim of this study was to evaluate the effect of prenatal and postnatal malnutrition on the intellectual functioning of early school-aged children. We followed the offspring of women who had participated in a trial of prenatal supplementation with different combinations of micronutrients and who remained resident in the study field. We measured their intellectual functioning using the Wechsler intelligence scale for children (WISC-IV). Height-for-age, weight-for-age, and body mass index (BMI)-for-age were used as anthropometric nutritional status indices. Four of the 5 composite scores derived from the WISC-IV, except for working memory index (WMI), were significantly lower in low birth weight children after adjusting for confounds. All 5 composite scores, including full-scale intelligence quotient (FSIQ), verbal comprehension index (VCI), WMI, perceptual reasoning index (PRI), and processing speed index (PSI) were significant lower in stunted and underweight children. The differences in the means of WISC-IV test scores were greatest between stunted and nonstunted children. The means for FSIQ, VCI, WMI, PRI, and PSI were as follows: 5.88 (95% confidence interval [CI]: 2.84–8.92), 5.08 (95% CI: 1.12–8.41), 4.71 (95% CI: 1.78–7.66), 6.13 (95% CI: 2.83–9.44), and 5.81 (95% CI: 2.61–9.00). These means were lower in stunted children after adjusting for confounds. Our results suggest the important influences of low birth weight and postnatal malnutrition (stunting, low body weight) on intellectual functioning in early school-aged children. PMID:27495020

Effect of prenatal and postnatal malnutrition on intellectual functioning in early school-aged children in rural western China.

PubMed

Li, Chao; Zhu, Ni; Zeng, Lingxia; Dang, Shaonong; Zhou, Jing; Yan, Hong

2016-08-01

The aim of this study was to evaluate the effect of prenatal and postnatal malnutrition on the intellectual functioning of early school-aged children. We followed the offspring of women who had participated in a trial of prenatal supplementation with different combinations of micronutrients and who remained resident in the study field. We measured their intellectual functioning using the Wechsler intelligence scale for children (WISC-IV). Height-for-age, weight-for-age, and body mass index (BMI)-for-age were used as anthropometric nutritional status indices. Four of the 5 composite scores derived from the WISC-IV, except for working memory index (WMI), were significantly lower in low birth weight children after adjusting for confounds. All 5 composite scores, including full-scale intelligence quotient (FSIQ), verbal comprehension index (VCI), WMI, perceptual reasoning index (PRI), and processing speed index (PSI) were significant lower in stunted and underweight children. The differences in the means of WISC-IV test scores were greatest between stunted and nonstunted children. The means for FSIQ, VCI, WMI, PRI, and PSI were as follows: 5.88 (95% confidence interval [CI]: 2.84-8.92), 5.08 (95% CI: 1.12-8.41), 4.71 (95% CI: 1.78-7.66), 6.13 (95% CI: 2.83-9.44), and 5.81 (95% CI: 2.61-9.00). These means were lower in stunted children after adjusting for confounds. Our results suggest the important influences of low birth weight and postnatal malnutrition (stunting, low body weight) on intellectual functioning in early school-aged children.

Early postnatal inhibition of serotonin synthesis results in long-term reductions of perseverative behaviors, but not aggression, in MAO A-deficient mice

PubMed Central

Bortolato, Marco; Godar, Sean C.; Tambaro, Simone; Li, Felix G.; Devoto, Paola; Coba, Marcelo P.; Chen, Kevin; Shih, Jean C.

2013-01-01

Monoamine oxidase (MAO) A, the major enzyme catalyzing the oxidative degradation of serotonin (5-hydroxytryptamine, 5-HT), plays a key role in emotional regulation. In humans and mice, MAO-A deficiency results in high 5-HT levels, antisocial, aggressive, and perseverative behaviors. We previously showed that the elevation in brain 5-HT levels in MAO-A knockout (KO) mice is particularly marked during the first two weeks of postnatal life. Building on this finding, we hypothesized that the reduction of 5-HT levels during these early stages may lead to enduring attenuations of the aggression and other behavioral aberrances observed in MAO-A KO mice. To test this possibility, MAO-A KO mice were treated with daily injections of a 5-HT synthesis blocker, the tryptophan hydroxylase inhibitor p-chloro-phenylalanine (pCPA, 300 mg/kg/day, IP), from postnatal day 1 through 7. As expected, this regimen significantly reduced 5-HT forebrain levels in MAO-A KO pups. These neurochemical changes persisted throughout adulthood, and resulted in significant reductions in marble-burying behavior, as well as increases in spontaneous alternations within a T-maze. Conversely, pCPA-treated MAO-A KO mice did not exhibit significant changes in anxiety-like behaviors in a novel open-field and elevated plus-maze; furthermore, this regimen did not modify their social deficits, aggressive behaviors and impairments in tactile sensitivity. Treatment with pCPA from postnatal day 8 through 14 elicited similar, yet milder, behavioral effects on marble-burying behavior. These results suggest that early developmental enhancements in 5-HT levels have long-term effects on the modulation of behavioral flexibility associated with MAO-A deficiency. PMID:23871843

Enhancement of NAD+-dependent SIRT1 deacetylase activity by methylselenocysteine resets the circadian clock in carcinogen-treated mammary epithelial cells

PubMed Central

Fang, Mingzhu; Guo, Wei-Ren; Park, Youngil; Kang, Hwan-Goo; Zarbl, Helmut

2015-01-01

We previously reported that dietary methylselenocysteine (MSC) inhibits N-methyl-N-nitrosourea (NMU)-induced mammary tumorigenesis by resetting circadian gene expression disrupted by the carcinogen at the early stage of tumorigenesis. To investigate the underlying mechanism, we developed a circadian reporter system comprised of human mammary epithelial cells with a luciferase reporter driven by the promoter of human PERIOD 2 (PER2), a core circadian gene. In this in vitro model, NMU disrupted cellular circadian rhythm in a pattern similar to that observed with SIRT1-specific inhibitors; in contrast, MSC restored the circadian rhythms disrupted by NMU and protected against SIRT1 inhibitors. Moreover, NMU inhibited intracellular NAD+/NADH ratio and reduced NAD+-dependent SIRT1 activity in a dose-dependent manner, while MSC restored NAD+/NADH and SIRT1 activity in the NMU-treated cells, indicating that the NAD+-SIRT1 pathway was targeted by NMU and MSC. In rat mammary tissue, a carcinogenic dose of NMU also disrupted NAD+/NADH oscillations and decreased SIRT1 activity; dietary MSC restored NAD+/NADH oscillations and increased SIRT1 activity in the mammary glands of NMU-treated rats. MSC-induced SIRT1 activity was correlated with decreased acetylation of BMAL1 and increased acetylation of histone 3 lysine 9 at the Per2 promoter E-Box in mammary tissue. Changes in SIRT1 activity were temporally correlated with loss or restoration of rhythmic Per2 mRNA expression in NMU-treated or MSC-rescued rat mammary glands, respectively. Together with our previous findings, these results suggest that enhancement of NAD+-dependent SIRT1 activity contributes to the chemopreventive efficacy of MSC by restoring epigenetic regulation of circadian gene expression at early stages of mammary tumorigenesis. PMID:26544624

Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain long-term plasticity in the embryonic mammary gland.

PubMed

Lilja, Anna M; Rodilla, Veronica; Huyghe, Mathilde; Hannezo, Edouard; Landragin, Camille; Renaud, Olivier; Leroy, Olivier; Rulands, Steffen; Simons, Benjamin D; Fre, Silvia

2018-06-01

Recent lineage tracing studies have revealed that mammary gland homeostasis relies on unipotent stem cells. However, whether and when lineage restriction occurs during embryonic mammary development, and which signals orchestrate cell fate specification, remain unknown. Using a combination of in vivo clonal analysis with whole mount immunofluorescence and mathematical modelling of clonal dynamics, we found that embryonic multipotent mammary cells become lineage-restricted surprisingly early in development, with evidence for unipotency as early as E12.5 and no statistically discernable bipotency after E15.5. To gain insights into the mechanisms governing the switch from multipotency to unipotency, we used gain-of-function Notch1 mice and demonstrated that Notch activation cell autonomously dictates luminal cell fate specification to both embryonic and basally committed mammary cells. These functional studies have important implications for understanding the signals underlying cell plasticity and serve to clarify how reactivation of embryonic programs in adult cells can lead to cancer.

Evolution of immune functions of the mammary gland and protection of the infant.

PubMed

Goldman, Armond S

2012-06-01

Abstract The evolution of immunological agents in milk is intertwined with the general aspects of the evolution of the mammary gland. In that respect, mammalian precursors emerged from basal amniotes some 300 million years ago. In contrast to the predominant dinosaurs, proto-mammals possessed a glandular skin. A secondary palate in the roof of the mouth that directed airflow from the nostrils to the oropharynx and thus allowed mammals to ingest and breathe simultaneously first appeared in cynodonts 230 million years ago. This set the stage for mammalian newborns to nurse from the future mammary gland. Interplays between environmental and genetic changes shaped mammalian evolution including the mammary gland from dermal glands some 160 millions of years ago. It is likely that secretions from early mammary glands provided nutrients and immunological agents for the infant. Natural selection culminated in milks uniquely suited to nourish and protect infants of each species. In human milk, antimicrobial, anti-inflammatory, and immunoregulatory agents and living leukocytes are qualitatively or quantitatively different from those in other mammalian milks. Those in human milk compensate for developmental delays in the immunological system of the recipient infant. Consequently, the immune system in human milk provided by evolution is much of the basis for encouraging breastfeeding for human infants.

Maternal nutrient restriction during late gestation and early postnatal growth in sheep differentially reset the control of energy metabolism in the gastric mucosa.

PubMed

Sebert, S P; Dellschaft, N S; Chan, L L Y; Street, H; Henry, M; Francois, C; Sharma, V; Fainberg, H P; Patel, N; Roda, J; Keisler, D; Budge, H; Symonds, M E

2011-07-01

Fetal growth restriction followed by accelerated postnatal growth contributes to impaired metabolic function in adulthood. The extent to which these outcomes may be mediated centrally within the hypothalamus, as opposed to in the periphery within the digestive tract, remains unknown. In a sheep model, we achieved intrauterine growth restriction experimentally by maternal nutrient restriction (R) that involved a 40% reduction in food intake through late gestation. R offspring were then either reared singly to accelerate postnatal growth (RA) or as twins and compared with controls also reared singly. From weaning, all offspring were maintained indoors until adulthood. A reduced litter size accelerated postnatal growth for only the first month of lactation. Independently from postnatal weight gain and later fat mass, R animals developed insulin resistance as adults. However, restricted accelerated offspring compared with both the control accelerated and restricted restricted offspring ate less and had higher fasting plasma leptin as adults, an adaptation which was accompanied by changes in energy sensing and cell proliferation within the abomasum. Additionally, although fetal restriction down-regulated gene expression of mammalian target of rapamycin and carnitine palmitoyltransferase 1-dependent pathways in the abomasum, RA offspring compensated for this by exhibiting greater activity of AMP-activated kinase-dependent pathways. This study demonstrates a role for perinatal nutrition in the peripheral control of food intake and in energy sensing in the gastric mucosal and emphasizes the importance of diet in early life in regulating energy metabolism during adulthood.

Activation of int-1 and int-2 loci in GRf mammary tumors.

PubMed

Gray, D A; Jackson, D P; Percy, D H; Morris, V L

1986-10-30

The Mtv-2 locus is known to be associated with a high mammary tumor incidence (97%) and early development of mammary tumors (3-13 months) in GR mice. However, it was not previously known whether the provirus which resides at the Mtv-2 locus is tumorigenic in and of itself or whether reintegration of proviruses generated from Mtv-2 is required for tumorigenesis. Foster-nursing GR mice on C57/BL mice eliminates the milk-borne source of GR virus, and allows the study of Mtv-2 derived proviruses alone. Using this approach, we have tested predictions which follow from the "positional" versus "reintegrational" models of tumorigenesis. Specifically, we have examined tumors from primary foster-nursed (GRf) mice to determine if MMTV proviruses derived from Mtv-2 were scattered randomly throughout the genome or were clustered in the vicinity of the int-1 and int-2 loci, which are thought to be associated with mammary tumorigenesis. It was found that the majority of spontaneous GRf mammary tumors that were tested have MMTV proviral integrations in either or both of the int-1 and int-2 loci and have transcription of either or both of the int loci. Tumors induced by Mtv-2, therefore, appear to have arisen via a mechanism similar to the activation of the int loci by exogenous (milk-borne) MMTV proviruses.

Mammary gland involution is associated with rapid down regulation of major mammary Ca**2+-ATPases

USDA-ARS?s Scientific Manuscript database

Sixty percent of calcium in milk is transported across the mammary cells apical membrane by the plasma membrane Ca**2+-ATPase 2 (PMCA2). The effect of abrupt cessation of milk production on the Ca**2+-ATPases and mammary calcium transport is unknown. We found that 24 hours after stopping milk prod...

Number and location of mouse mammary tumor virus proviral DNA in mouse DNA of normal tissue and of mammary tumors.

PubMed Central

Groner, B; Hynes, N E

1980-01-01

The Southern DNA filter transfer technique was used to characterize the genomic location of the mouse mammary tumor proviral DNA in different inbred strains of mice. Two of the strains (C3H and CBA) arose from a cross of a Bagg albino (BALB/c) mouse and a DBA mouse. The mouse mammary tumor virus-containing restriction enzyme DNA fragments of these strains had similar patterns, suggesting that the proviruses of these mice are in similar genomic locations. Conversely, the pattern arising from the DNA of the GR mouse, a strain genetically unrelated to the others, appeared different, suggesting that its mouse mammary tumor proviruses are located in different genomic sites. The structure of another gene, that coding for beta-globin, was also compared. The mice strains which we studied can be categorized into two classes, expressing either one or two beta-globin proteins. The macroenvironment of the beta-globin gene appeared similar among the mice strains belonging to one genetic class. Female mice of the C3H strain exogenously transmit mouse mammary tumor virus via the milk, and their offspring have a high incidence of mammary tumor occurrence. DNA isolated from individual mammary tumors taken from C3H mice or from BALB/c mice foster nursed on C3H mothers was analyzed by the DNA filter transfer technique. Additional mouse mammary tumor virus-containing fragments were found in the DNA isolated from each mammary tumor. These proviral sequences were integrated into different genomic sites in each tumor. Images PMID:6245257

A missense mutation in myosin VIIA prevents aminoglycoside accumulation in early postnatal cochlear hair cells.

PubMed

Richardson, G P; Forge, A; Kros, C J; Marcotti, W; Becker, D; Williams, D S; Thorpe, J; Fleming, J; Brown, S D; Steel, K P

1999-11-28

Myosin VIIA is expressed by sensory hair cells in the inner ear and proximal tubule cells in the kidney, the two primary targets of aminoglycoside antibiotics. Using cochlear cultures prepared from early postnatal Myo7a6J mice with a missense mutation in the head region of the myosin VIIA molecule we show that this myosin is required for aminoglycoside accumulation in cochlear hair cells. Hair cells in homozygous mutant Myo7a6J cochlear cultures have disorganized hair bundles, but are otherwise morphologically normal and transduce. However, and in contrast to hair cells from heterozygous Myo7a6J cultures, the homozygous Myo7a6J hair cells do not accumulate [3H]gentamicin and do not exhibit an ototoxic response on exposure to aminoglycoside. Possible roles for myosin VIIA in the process of aminoglycoside accumulation are discussed.

Postnatal care in the community: report of an evaluation of birthing women's assessments of a postnatal home-care programme.

PubMed

Zadoroznyj, Maria

2007-01-01

For more than a decade, there has been a strong trend in many Western countries to decrease the length of time that women spend in hospital following childbirth. The research evidence regarding the consequences of early discharge for mothers and babies is mixed. Recent evidence has suggested that early discharge may not be randomly distributed across all sociodemographic groups of birthing women, and that the structures of home care have an important influence on maternal and child outcomes. In the context of decreasing lengths of hospital stay, the aim of the present study was to evaluate a new postnatal home support worker introduced into a geographically defined catchment area of a metropolitan hospital in South Australia. The evaluation included a formative process component to monitor recruitment strategies into the programme, as well as summative evaluation of a number of projected programme outcomes. The research methods used included interviews with antenatal women (n = 20) about their knowledge of and attitudes to the programme, and interviews with postnatal women (n = 63) about their transition home experience and assessment of the programme. Secondary analysis of client satisfaction surveys (n = 163) and aggregate breast-feeding data was also conducted. The results concur with previous research findings regarding the importance of rest and practical, home-based support in the postnatal period to maternal well-being, successful bonding and transition to motherhood. The results demonstrate the importance of well-structured home support services to maternal satisfaction and maternal well-being through the provision of physical, social and emotional care and support in the home.

Microenvironmental Regulation of Mammary Carcinogenesis

DTIC Science & Technology

2008-06-01

cells. These models share many of the hallmarks of multistage human breast cancer development including histological disease progression and immune cell... developed by Muller and colleagues20, represents a reasonable recapitulation of late-stage human breast cancer as determined by histological progression ...Annual Progress Report d. Develop a profile of proteolytic activities in normal and neoplastic mammary tissues from mouse models of mammary

Activation of GABA-A receptors during postnatal brain development increases anxiety- and depression-related behaviors in a time- and dose-dependent manner in adult mice.

PubMed

Salari, Ali-Akbar; Bakhtiari, Amir; Homberg, Judith R

2015-08-01

Disturbances of the gamma-amino butyric acid-ergic (GABAergic) system during postnatal development can have long-lasting consequences for later life behavior, like the individual's response to stress. However, it is unclear which postnatal windows of sensitivity to GABA-ergic modulations are associated with what later-life behavioral outcomes. Therefore, we sought to determine whether neonatal activation of the GABA-A receptor during two postnatal periods, an early window (postnatal day 3-5) and a late window (postnatal day 14-16), can affect anxiety- and depression-related behaviors in male mice in later life. To this end, mice were treated with either saline or muscimol (50, 100, 200, 300 and 500μg/kg) during the early and late postnatal periods. An additional group of mice was treated with the GABA-A receptor antagonist bicuculline+muscimol. When grown to adulthood male mice were exposed to behavioral tests to measure anxiety- and depression-related behaviors. Baseline and stress-induced corticosterone (CORT) levels were also measured. The results indicate that early postnatal and to a lesser extent later postnatal exposure to the GABA-A receptor agonist muscimol increased anxiety-like behavior and stress-induced CORT levels in adults. Moreover, the early postnatal treatment with muscimol increased depression-like behavior with increasing baseline CORT levels. The anxiogenic and depression-like later-life consequences could be antagonized by bicuculline. Our findings suggest that GABA-A receptor signaling during early-life can influence anxiety- and depression-related behaviors in a time- and dose-dependent manner in later life. Our findings help to increase insight in the developmental mechanisms contributing to stress-related disorders. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Mammary Cancer and Activation of Transposable Elements

DTIC Science & Technology

2015-03-01

EGFP). No other cell type in the mammary fat pad was observed to express EGFP. Wholemount and FACS analyses of mammary fat pads after involution from...were sacrificed for PI-MEC isolation in groups of up to 4 control or cancer-prone uniparous or triparous females. Both 4 th mammary fat pads were...to unknown reason (n=46), and smaller numbers of animals with various conditions (malocclusion, head tilt , dystocia, respiratory complaints, identity

Insulin-like growth factor binding proteins initiate cell death and extracellular matrix remodeling in the mammary gland.

PubMed

Flint, D J; Boutinaud, M; Tonner, E; Wilde, C J; Hurley, W; Accorsi, P A; Kolb, A F; Whitelaw, C B A; Beattie, J; Allan, G J

2005-08-01

We have demonstrated that insulin-like growth factor binding protein-5 (IGFBP-5) production by mammary epithelial cells increases dramatically during forced involution of the mammary gland in rats, mice and pigs. We proposed that growth hormone (GH) increases the survival factor IGF-I, whilst prolactin (PRL) enhances the effects of GH by decreasing the concentration of IGFBP-5, which would otherwise inhibit the actions of IGFs. To demonstrate a causal relationship between IGFBP-5 and cell death, we created transgenic mice expressing IGFBP-5, specifically, in the mammary gland. DNA content in the mammary glands of transgenic mice was decreased as early as day 10 of pregnancy. Mammary cell number and milk synthesis were both decreased by approximately 50% during the first 10 days of lactation. The concentrations of the pro-apoptotic molecule caspase-3 was increased in transgenic animals whilst the concentrations of two pro-survival molecules Bcl-2 and Bcl-x were both decreased. In order to examine whether IGFBP-5 acts by inhibiting the survival effect of IGF-I, we examined IGF receptor- and Akt-phoshorylation and showed that both were inhibited. These studies also indicated that the effects of IGFBP-5 could be mediated in part by IGF-independent effects involving potential interactions with components of the extracellular matrix involved in tissue remodeling, such as components of the plasminogen system, and the matrix metallo-proteinases (MMPs). Mammary development was normalised in transgenic mice by R3-IGF-I, an analogue of IGF-I which binds weakly to IGFBPs, although milk production was only partially restored. In contrast, treatment with prolactin was able to inhibit early involutionary processes in normal mice but was unable to prevent this in mice over-expressing IGFBP-5, although it was able to inhibit activation of MMPs. Thus, IGFBP-5 can simultaneously inhibit IGF action and activate the plasminogen system thereby coordinating cell death and tissue

Regulation of mammary gland sensitivity to thyroid hormones during the transition from pregnancy to lactation.

PubMed

Capuco, A V; Connor, E E; Wood, D L

2008-10-01

Thyroid hormones are galactopoietic and help to establish the mammary gland's metabolic priority during lactation. Expression patterns for genes that can alter tissue sensitivity to thyroid hormones and thyroid hormone activity were evaluated in the mammary gland and liver of cows at 53, 35, 20, and 7 days before expected parturition, and 14 and 90 days into the subsequent lactation. Transcript abundance for the three isoforms of iodothyronine deiodinase, type I (DIO1), type II (DIO2) and type III (DIO3), thyroid hormone receptors alpha1 (TRalpha1), alpha2 (TRalpha2) and beta1 (TRbeta1), and retinoic acid receptors alpha (RXRalpha) and gamma (RXRgamma), which act as coregulators of thyroid hormone receptor action, were evaluated by quantitative RT-PCR. The DIO3 is a 5-deiodinase that produces inactive iodothyronine metabolites, whereas DIO1 and DIO2 generate the active thyroid hormone, triiodothyronine, from the relatively inactive precursor, thyroxine. Low copy numbers of DIO3 transcripts were present in mammary gland and liver. DIO2 was the predominant isoform expressed in mammary gland and DIO1 was the predominant isoform expressed in liver. Quantity of DIO1 mRNA in liver tissues did not differ with physiological state, but tended to be lowest during lactation. Quantity of DIO2 mRNA in mammary gland increased during lactation (P < 0.05), with copy numbers at 90 days of lactation 6-fold greater than at 35 and 20 days prepartum. When ratios of DIO2/DIO3 mRNA were evaluated, the increase was more pronounced (>100-fold). Quantity of TRbeta1 mRNA in mammary gland increased with onset of lactation, whereas TRalpha1 and TRalpha2 transcripts did not vary with physiological state. Conversely, quantity of RXRalpha mRNA decreased during late gestation to low levels during early lactation. Data suggest that increased expression of mammary TRbeta1 and DIO2, and decreased RXRalpha, provide a mechanism to increase thyroid hormone activity within the mammary gland during

Oxygen-sensitive regulation and neuroprotective effects of growth hormone-dependent growth factors during early postnatal development.

PubMed

Jung, Susan; Boie, Gudrun; Doerr, Helmuth-Guenther; Trollmann, Regina

2017-04-01

Perinatal hypoxia severely disrupts metabolic and somatotrophic development, as well as cerebral maturational programs. Hypoxia-inducible transcription factors (HIFs) represent the most important endogenous adaptive mechanisms to hypoxia, activating a broad spectrum of growth factors that contribute to cell survival and energy homeostasis. To analyze effects of systemic hypoxia and growth hormone (GH) therapy (rhGH) on HIF-dependent growth factors during early postnatal development, we compared protein (using ELISA) and mRNA (using quantitative RT PCR) levels of growth factors in plasma and brain between normoxic and hypoxic mice (8% O 2 , 6 h; postnatal day 7 , P7) at P14. Exposure to hypoxia led to reduced body weight ( P < 0.001) and length ( P < 0.04) compared with controls and was associated with significantly reduced plasma levels of mouse GH ( P < 0.01) and IGF-1 ( P < 0.01). RhGH abrogated these hypoxia-induced changes of the GH/IGF-1 axis associated with normalization of weight and length gain until P14 compared with controls. In addition, rhGH treatment increased cerebral IGF-1, IGF-2, IGFBP-2, and erythropoietin mRNA levels, resulting in significantly reduced apoptotic cell death in the hypoxic, developing mouse brain. These data indicate that rhGH may functionally restore hypoxia-induced systemic dysregulation of the GH/IGF-1 axis and induce upregulation of neuroprotective, HIF-dependent growth factors in the hypoxic developing brain. Copyright © 2017 the American Physiological Society.

SOCS3 promotes apoptosis of mammary differentiated cells.

PubMed

Le Provost, Fabienne; Miyoshi, Keiko; Vilotte, Jean-Luc; Bierie, Brian; Robinson, Gertraud W; Hennighausen, Lothar

2005-12-30

Growth and function of the mammary gland is regulated by cytokines and modulated by suppressor of cytokine signalling (SOCS) proteins. In vitro experiments demonstrated that SOCS3 can inhibit PRL induction of milk protein gene expression and STAT5 activation. We explored the SOCS3 expression pattern during mouse mammary development and its regulation by PRL and GH in wild-type and STAT5a-null mammary tissue. Our results suggest that, in vivo, PRL stimulates SOCS3 expression in stromal adipocytes, independently of STAT5a stimulation. In mammary epithelial cells, SOCS3 expression appears to be related to STAT3 activation. Together, our results are consistent with a role of SOCS3 in the mammary gland by promoting apoptosis of differentiated cells (adipocytes during gestation and epithelial cells during involution).

First-time fathers' postnatal experiences and support needs: A descriptive qualitative study.

PubMed

Shorey, Shefaly; Dennis, Cindy-Lee; Bridge, Shiho; Chong, Yap Seng; Holroyd, Eleanor; He, Hong-Gu

2017-12-01

To explore first-time fathers' postnatal experiences and support needs in the early postpartum period. The postnatal period is a stressful transition period for new fathers. It is imperative to understand their needs and experiences to provide appropriate support for them. The majority of previous studies were based in Western countries and explored fathers' needs during pregnancy and childbirth, with few studies conducted in the postnatal period. In Singapore, a multiracial society with differing paternal cultural values from its Western counterparts, there is considerable need to examine the experiences and needs of first-time fathers. A descriptive qualitative design was used. Data were collected from November 2015-January 2016. Fifteen first-time fathers were recruited from two postnatal wards of a public hospital, using a purposive sampling method. A semi-structured interview guide was used to conduct face-to-face interviews. A thematic analysis was conducted and ethics approval was sought for this study. Four overarching themes and seventeen subthemes were generated. The four overarching themes were: (1) No sense of reality to sense of responsibility; (2) Unprepared and challenged; (3) Support: needs, sources, experience and attitude; and (4) Future help for fathers. Fathers undergo a transition phase where they have unmet support needs during the early postnatal period. Understanding and addressing these needs may facilitate smooth transition to fatherhood. This study's findings can be used to involve fathers and design future supportive educational programs to promote positive parenting experiences and family dynamics. © 2017 John Wiley & Sons Ltd.

Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life.

PubMed

Smith, Dani; Aherrera, Angela; Lopez, Armando; Neptune, Enid; Winickoff, Jonathan P; Klein, Jonathan D; Chen, Gang; Lazarus, Philip; Collaco, Joseph M; McGrath-Morrow, Sharon A

2015-01-01

Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains. Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not. Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth.

Participation of the Olfactory Bulb in Circadian Organization during Early Postnatal Life in Rabbits

PubMed Central

Navarrete, Erika; Ortega-Bernal, Juan Roberto; Trejo-Muñoz, Lucero; Díaz, Georgina; Montúfar-Chaveznava, Rodrigo; Caldelas, Ivette

2016-01-01

Experimental evidence indicates that during pre-visual stages of development in mammals, circadian regulation is still not under the control of the light-entrainable hypothalamic pacemaker, raising the possibility that the circadian rhythmicity that occurs during postnatal development is under the control of peripheral oscillators, such as the main olfactory bulb (MOB). We evaluated the outcome of olfactory bulbectomy on the temporal pattern of core body temperature and gross locomotor activity in newborn rabbits. From postnatal day 1 (P1), pups were randomly assigned to one of the following conditions: intact pups (INT), intact pups fed by enteral gavage (INT+ENT), sham operated pups (SHAM), pups with unilateral lesions of the olfactory bulb (OBx-UNI), and pups with bilateral lesions of the olfactory bulb (OBx-BI). At the beginning of the experiment, from P1-8, the animals in all groups were fed at 11:00, from P9-13 the feeding schedule was delayed 6 h (17:00), and finally, from P14-15 the animals were subjected to fasting conditions. The rabbit pups of the INT, INT+ENT, SHAM and OBx-UNI groups exhibited a clear circadian rhythmicity in body temperature and locomotor activity, with a conspicuous anticipatory rise hours prior to the nursing or feeding schedule, which persisted even during fasting conditions. In addition, phase delays in the nursing or feeding schedule induced a clear phase shift in both parameters. In contrast, the OBx-BI group exhibited atypical rhythmicity in both parameters under entrained conditions that altered the anticipatory component, as well as deficient phase control of both rhythms. The present results demonstrate that the expression of circadian rhythmicity at behavioral and physiological levels during early stages of rabbit development largely depends on the integrity of the main olfactory bulb. PMID:27305041

Prevalence and risk factors for postnatal depression in Sabah, Malaysia: a cohort study.

PubMed

Mohamad Yusuff, Aza Sherin; Tang, Li; Binns, Colin W; Lee, Andy H

2015-03-01

Postnatal depression can have serious consequences for both the mother and infant. However, epidemiological data required to implement appropriate early prevention are still lacking in Malaysia. To investigate the prevalence of postnatal depression within six months postpartum and associated risk factors among women in Sabah, Malaysia. A prospective cohort study of 2072 women was conducted in Sabah during 2009-2010. Participants were recruited at 36-38 weeks of gestation and followed up at 1, 3 and 6 months postpartum. The presence of depressive symptoms was assessed using the validated Malay version of the Edinburgh Postnatal Depression Scale. Logistic regression analyses were performed to ascertain risk factors associated with postnatal depression. Overall, 14.3% of mothers (95% confidence interval (CI) 12.5-16.2%) had experienced depression within the first six months postpartum. Women depressed during pregnancy (odds ratio (OR) 3.71, 95% CI 2.46-5.60) and those with consistent worries about the newborn (OR 1.68, 95% CI 1.16-2.42) were more likely to suffer from depression after childbirth. Women whose husband assisted with infant care (OR 0.43, 95% CI 0.20-0.97) and mothers who were satisfied with their marital relationship (OR 0.27, 95% CI 0.09-0.81) appeared to incur a reduced risk of postnatal depression. A substantial proportion of mothers suffered from postnatal depression in Sabah, Malaysia. Screening and intervention programmes targeting vulnerable subgroups of women during antenatal and early postpartum periods are recommended to deal with the problem. Copyright © 2014 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

CLINICOPATHOLOGIC FEATURES OF MAMMARY MASSES IN CAPTIVE LIONS (PANTHERA LEO).

PubMed

Sadler, Ryan A; Craig, Linden E; Ramsay, Edward C; Helmick, Kelly; Collins, Darin; Garner, Michael M

2016-03-01

A multi-institutional retrospective analysis of 330 pathology accessions from 285 different lions found 15 captive, female African lions (Panthera leo) with confirmed mammary masses. Aside from the presence of a mammary mass, the most common initial clinical sign was inappetence. Histologic diagnoses were predominantly adenocarcinoma (n = 12), though two benign masses (mammary hyperplasia and a mammary cyst) and one squamous cell carcinoma were identified. Nine of 13 malignant tumors had metastasized to lymph nodes or viscera at the time of necropsy. Six lions with adenocarcinoma and two lions with benign mammary masses had received hormonal contraception, though little evidence of mammary lobular hyperplasia was seen in association with the adenocarcinomas. The most common concurrent disease processes found at necropsy were chronic urinary tract disease and other malignancies. These cases demonstrate that mammary malignancies occur in captive lions and frequently metastasize.

Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats

PubMed Central

Kakehashi, Anna; Yoshida, Midori; Tago, Yoshiyuki; Ishii, Naomi; Okuno, Takahiro; Gi, Min; Wanibuchi, Hideki

2016-01-01

Pueraria mirifica (PM), a plant whose dried and powdered tuberous roots are now widely used in rejuvenating preparations to promote youthfulness in both men and women, may have major estrogenic influence. In this study, we investigated modifying effects of PM at various doses on mammary and endometrial carcinogenesis in female Donryu rats. Firstly, PM administered to ovariectomized animals at doses of 0.03%, 0.3%, and 3% in a phytoestrogen-low diet for 2 weeks caused significant increase in uterus weight. Secondly, a 4 week PM application to non-operated rats at a dose of 3% after 7,12-dimethylbenz[a]anthracene (DMBA) initiation resulted in significant elevation of cell proliferation in the mammary glands. In a third experiment, postpubertal administration of 0.3% (200 mg/kg body weight (b.w.)/day) PM to 5-week-old non-operated animals for 36 weeks following initiation of mammary and endometrial carcinogenesis with DMBA and N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG), respectively, resulted in significant increase of mammary adenocarcinoma incidence. A significant increase of endometrial atypical hyperplasia multiplicity was also observed. Furthermore, PM at doses of 0.3%, and more pronouncedly, at 1% induced dilatation, hemorrhage and inflammation of the uterine wall. In conclusion, postpubertal long-term PM administration to Donryu rats exerts estrogenic effects in the mammary gland and uterus, and at a dose of 200 mg/kg b.w./day was found to promote mammary carcinogenesis initiated by DMBA. PMID:27827907

Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats.

PubMed

Kakehashi, Anna; Yoshida, Midori; Tago, Yoshiyuki; Ishii, Naomi; Okuno, Takahiro; Gi, Min; Wanibuchi, Hideki

2016-11-04

Pueraria mirifica (PM), a plant whose dried and powdered tuberous roots are now widely used in rejuvenating preparations to promote youthfulness in both men and women, may have major estrogenic influence. In this study, we investigated modifying effects of PM at various doses on mammary and endometrial carcinogenesis in female Donryu rats. Firstly, PM administered to ovariectomized animals at doses of 0.03%, 0.3%, and 3% in a phytoestrogen-low diet for 2 weeks caused significant increase in uterus weight. Secondly, a 4 week PM application to non-operated rats at a dose of 3% after 7,12-dimethylbenz[a]anthracene (DMBA) initiation resulted in significant elevation of cell proliferation in the mammary glands. In a third experiment, postpubertal administration of 0.3% (200 mg/kg body weight (b.w.)/day) PM to 5-week-old non-operated animals for 36 weeks following initiation of mammary and endometrial carcinogenesis with DMBA and N -ethyl- N '-nitro- N -nitrosoguanidine (ENNG), respectively, resulted in significant increase of mammary adenocarcinoma incidence. A significant increase of endometrial atypical hyperplasia multiplicity was also observed. Furthermore, PM at doses of 0.3%, and more pronouncedly, at 1% induced dilatation, hemorrhage and inflammation of the uterine wall. In conclusion, postpubertal long-term PM administration to Donryu rats exerts estrogenic effects in the mammary gland and uterus, and at a dose of 200 mg/kg b.w./day was found to promote mammary carcinogenesis initiated by DMBA.

Postnatal proteasome inhibition induces neurodegeneration and cognitive deficiencies in adult mice: a new model of neurodevelopment syndrome.

PubMed

Romero-Granados, Rocío; Fontán-Lozano, Ángela; Aguilar-Montilla, Francisco Javier; Carrión, Ángel Manuel

2011-01-01

Defects in the ubiquitin-proteasome system have been related to aging and the development of neurodegenerative disease, although the effects of deficient proteasome activity during early postnatal development are poorly understood. Accordingly, we have assessed how proteasome dysfunction during early postnatal development, induced by administering proteasome inhibitors daily during the first 10 days of life, affects the behaviour of adult mice. We found that this regime of exposure to the proteasome inhibitors MG132 or lactacystin did not produce significant behavioural or morphological changes in the first 15 days of life. However, towards the end of the treatment with proteasome inhibitors, there was a loss of mitochondrial markers and activity, and an increase in DNA oxidation. On reaching adulthood, the memory of mice that were injected with proteasome inhibitors postnatally was impaired in hippocampal and amygdala-dependent tasks, and they suffered motor dysfunction and imbalance. These behavioural deficiencies were correlated with neuronal loss in the hippocampus, amygdala and brainstem, and with diminished adult neurogenesis. Accordingly, impairing proteasome activity at early postnatal ages appears to cause morphological and behavioural alterations in adult mice that resemble those associated with certain neurodegenerative diseases and/or syndromes of mental retardation.

Leukocyte populations and cytokine expression in the mammary gland in a mouse model of Streptococcus agalactiae mastitis.

PubMed

Trigo, Gabriela; Dinis, Márcia; França, Angela; Bonifácio Andrade, Elva; Gil da Costa, Rui M; Ferreira, Paula; Tavares, Delfina

2009-07-01

Streptococcus agalactiae is a contagious, mastitis-causing pathogen that is highly adapted to survive in the bovine mammary gland. This study used a BALB/c mouse model of Streptococcus agalactiae mastitis to evaluate leukocyte populations in regional lymph nodes and cytokine expression in the mammary gland involved in the immune response against Streptococcus agalactiae. It was found that the bacteria replicated efficiently in the mammary gland, peaking after 24 h and increasing by 100-fold. Dissemination of bacteria to systemic organs was observed 6 h after infection. At the same time, a massive infiltration of polymorphonuclear cells and an increase in the inflammatory cytokines interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha were detected in mammary glands, indicating an early inflammatory response. A decrease in the levels of inflammatory cytokines in mammary glands was observed 72 h after infection, accompanied by an increase in the levels of IL-12 and IL-10, which were related to a gradual decrease in bacterial load. An increase in the number of macrophages and B220(+) lymphocytes and similar increases in both CD4(+) and CD8(+) T cells in regional lymph nodes were observed, being most pronounced 5 days after infection. Moreover, increased levels of anti-Streptococcus agalactiae antibodies in the mammary gland were observed 10 days after infection. Overall, these data suggest that the host exhibits both innate and acquired immune responses in response to Streptococcus agalactiae mastitis.

The mammary cellular hierarchy and breast cancer.

PubMed

Oakes, Samantha R; Gallego-Ortega, David; Ormandy, Christopher J

2014-11-01

Advances in the study of hematopoietic cell maturation have paved the way to a deeper understanding the stem and progenitor cellular hierarchy in the mammary gland. The mammary epithelium, unlike the hematopoietic cellular hierarchy, sits in a complex niche where communication between epithelial cells and signals from the systemic hormonal milieu, as well as from extra-cellular matrix, influence cell fate decisions and contribute to tissue homeostasis. We review the discovery, definition and regulation of the mammary cellular hierarchy and we describe the development of the concepts that have guided our investigations. We outline recent advances in in vivo lineage tracing that is now challenging many of our assumptions regarding the behavior of mammary stem cells, and we show how understanding these cellular lineages has altered our view of breast cancer.

Genistein-mediated inhibition of mammary stromal adipocyte differentiation limits expansion of mammary stem/progenitor cells by paracrine signaling

USDA-ARS?s Scientific Manuscript database

Mammary adiposity may contribute to breast cancer development and progression by releasing cytokines and other inflammatory mediators that promote mammary epithelial proliferation. We evaluated the effects of soy isoflavone genistein (GEN) on the adipogenic differentiation of a SV40-immortalized mou...

Association between maternal depressive symptoms in the early post-natal period and responsiveness in feeding at child age 2 years.

PubMed

Mallan, Kimberley M; Daniels, Lynne A; Wilson, Jacinda L; Jansen, Elena; Nicholson, Jan M

2015-10-01

Maternal depression is a known risk factor for poor outcomes for children. Pathways to these poor outcomes relate to reduced maternal responsiveness or sensitivity to the child. Impaired responsiveness potentially impacts the feeding relationship and thus may be a risk factor for inappropriate feeding practices. The aim of this study was to examine the longitudinal relationships between self-reported maternal post-natal depressive symptoms at child age 4 months and feeding practices at child age 2 years in a community sample. Participants were Australian first-time mothers allocated to the control group of the NOURISH randomized controlled trial when infants were 4 months old. Complete data from 211 mothers (of 346 allocated) followed up when their children were 2 years of age (51% girls) were available for analysis. The relationship between Edinburgh Postnatal Depression Scale (EPDS) score (child age 4 months) and child feeding practices (child age 2 years) was tested using hierarchical linear regression analysis adjusted for maternal and child characteristics. Higher EPDS score was associated with less responsive feeding practices at child age 2 years: greater pressure [β = 0.18, 95% confidence interval (CI): 0.04-0.32, P = 0.01], restriction (β = 0.14, 95% CI: 0.001-0.28, P = 0.05), instrumental (β = 0.14, 95% CI: 0.005-0.27, P = 0.04) and emotional (β = 0.15, 95% CI: 0.01-0.29, P = 0.03) feeding practices (ΔR(2) values: 0.02-0.03, P < 0.05). This study provides evidence for the proposed link between maternal post-natal depressive symptoms and lower responsiveness in child feeding. These findings suggest that the provision of support to mothers experiencing some levels of depressive symptomatology in the early post-natal period may improve responsiveness in the child feeding relationship. © 2014 John Wiley & Sons Ltd.

Elevated circulating IGF-I promotes mammary gland development and proliferation.

PubMed

Cannata, Dara; Lann, Danielle; Wu, Yingjie; Elis, Sebastien; Sun, Hui; Yakar, Shoshana; Lazzarino, Deborah A; Wood, Teresa L; Leroith, Derek

2010-12-01

Animal studies have shown that IGF-I is essential for mammary gland development. Previous studies have suggested that local IGF-I rather than circulating IGF-I is the major mediator of mammary gland development. In the present study we used the hepatic IGF-I transgenic (HIT) and IGF-I knockout/HIT (KO-HIT) mouse models to examine the effects of enhanced circulating IGF-I on mammary development in the presence and absence of local IGF-I. HIT mice express the rat IGF-I transgene under the transthyretin promoter in the liver and have elevated circulating IGF-I and normal tissue IGF-I levels. The KO-HIT mice have no tissue IGF-I and increased circulating IGF-I. Analysis of mammary gland development reveals a greater degree of complexity in HIT mice as compared to control and KO-HIT mice, which demonstrate similar degrees of mammary gland complexity. Immunohistochemical evaluation of glands of HIT mice also suggests an enhanced degree of proliferation of the mammary gland, whereas KO-HIT mice exhibit mammary gland proliferation similar to control mice. In addition, HIT mice have a higher percentage of proliferating myoepithelial and luminal cells than control mice, whereas KO-HIT mice have an equivalent percentage of proliferating myoepithelial and luminal cells as control mice. Thus, our findings show that elevated circulating IGF-I levels are sufficient to promote normal pubertal mammary epithelial development. However, HIT mice demonstrate more pronounced mammary gland development when compared to control and KO-HIT mice. This suggests that both local and endocrine IGF-I play roles in mammary gland development and that elevated circulating IGF-I accelerates mammary epithelial proliferation.

Maternal postnatal mental health and later emotional-behavioural development of children: the mediating role of parenting behaviour.

PubMed

Giallo, R; Cooklin, A; Wade, C; D'Esposito, F; Nicholson, J M

2014-05-01

Maternal postnatal mental health difficulties have been associated with poor outcomes for children. One mechanism by which parent mental health can impact on children's outcomes is via its effects on parenting behaviour. The longitudinal relationships between maternal postnatal distress, parenting warmth, hostility and child well-being at age seven were examined for 2200 families participating in a population-based longitudinal study of Australian children. The relationship between postnatal distress and children's later emotional-behavioural development was mediated by parenting hostility, but not parenting warmth, even after accounting for concurrent maternal mental health. Postnatal distress was more strongly associated with lower parenting warmth for mothers without a past history of depression compared with mothers with a past history of depression. These findings underscore the contribution of early maternal well-being to later parenting and child outcomes, highlighting the importance of mental health and parenting support in the early parenting years. Implications for policy and practice are discussed. © 2013 John Wiley & Sons Ltd.

Prenatal hydronephrosis: postnatal evaluation and management.

PubMed

Vemulakonda, Vijaya; Yiee, Jenny; Wilcox, Duncan T

2014-08-01

Congenital hydronephrosis is one of the most common anomalies identified on antenatal ultrasound. The underlying etiology of congenital hydronephrosis is multifold, ranging from transient hydronephrosis in utero to clinically significant congenital anomalies of the kidney and urinary tract. While traditional management of hydronephrosis was aimed at relieving symptoms, the advent of routine prenatal ultrasound has led to a shift in the goal of treatment to prevention of renal injury in the asymptomatic patient. However, despite this focus on renal preservation, the diagnostic criteria for identification of children "at risk" for renal damage that can be alleviated by surgical treatment remain a subject of debate. Both antenatal and postnatal imaging studies have been evaluated as indicators for potential reversible renal damage and have been used as potential indicators of the need for surgical intervention. The aim of this review is to discuss the current literature regarding the role of postnatal clinical and radiographic evaluation to identify children who may benefit from early surgical intervention.

Downregulation of ATM Gene and Protein Expression in Canine Mammary Tumors.

PubMed

Raposo-Ferreira, T M M; Bueno, R C; Terra, E M; Avante, M L; Tinucci-Costa, M; Carvalho, M; Cassali, G D; Linde, S D; Rogatto, S R; Laufer-Amorim, R

2016-11-01

The ataxia telangiectasia mutated (ATM) gene encodes a protein associated with DNA damage repair and maintenance of genomic integrity. In women, ATM transcript and protein downregulation have been reported in sporadic breast carcinomas, and the absence of ATM protein expression has been associated with poor prognosis. The aim of this study was to evaluate ATM gene and protein expression in canine mammary tumors and their association with clinical outcome. ATM gene and protein expression was evaluated by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, respectively, in normal mammary gland samples (n = 10), benign mammary tumors (n = 11), nonmetastatic mammary carcinomas (n = 19), and metastatic mammary carcinomas (n = 11). Lower ATM transcript levels were detected in benign mammary tumors and carcinomas compared with normal mammary glands (P = .011). Similarly, lower ATM protein expression was observed in benign tumors (P = .0003), nonmetastatic mammary carcinomas (P < .0001), and the primary sites of metastatic carcinomas (P < .0001) compared with normal mammary glands. No significant differences in ATM gene or protein levels were detected among benign tumors and nonmetastatic and metastatic mammary carcinomas (P > .05). The levels of ATM gene or protein expression were not significantly associated with clinical and pathological features or with survival. Similar to human breast cancer, the data in this study suggest that ATM gene and protein downregulation is involved in canine mammary gland tumorigenesis. © The Author(s) 2016.

Peroxisomal membrane channel Pxmp2 in the mammary fat pad is essential for stromal lipid homeostasis and for development of mammary gland epithelium in mice.

PubMed

Vapola, Miia H; Rokka, Aare; Sormunen, Raija T; Alhonen, Leena; Schmitz, Werner; Conzelmann, Ernst; Wärri, Anni; Grunau, Silke; Antonenkov, Vasily D; Hiltunen, J Kalervo

2014-07-01

To understand the functional role of the peroxisomal membrane channel Pxmp2, mice with a targeted disruption of the Pxmp2 gene were generated. These mice were viable, grew and bred normally. However, Pxmp2(-/-) female mice were unable to nurse their pups. Lactating mammary gland epithelium displayed secretory lipid droplets and milk proteins, but the size of the ductal system was greatly reduced. Examination of mammary gland development revealed that retarded mammary ductal outgrowth was due to reduced proliferation of epithelial cells during puberty. Transplantation experiments established the Pxmp2(-/-) mammary stroma as a tissue responsible for suppression of epithelial growth. Morphological and biochemical examination confirmed the presence of peroxisomes in the mammary fat pad adipocytes, and functional Pxmp2 was detected in the stroma of wild-type mammary glands. Deletion of Pxmp2 led to an elevation in the expression of peroxisomal proteins in the mammary fat pad but not in liver or kidney of transgenic mice. Lipidomics of Pxmp2(-/-)mammary fat pad showed a decrease in the content of myristic acid (C14), a principal substrate for protein myristoylation and a potential peroxisomal β-oxidation product. Analysis of complex lipids revealed a reduced concentration of a variety of diacylglycerols and phospholipids containing mostly polyunsaturated fatty acids that may be caused by activation of lipid peroxidation. However, an antioxidant-containing diet did not stimulate mammary epithelial proliferation in Pxmp2(-/-) mice. The results point to disturbances of lipid metabolism in the mammary fat pad that in turn may result in abnormal epithelial growth. The work reveals impaired mammary gland development as a new category of peroxisomal disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

Regulated expression of homeobox genes Msx-1 and Msx-2 in mouse mammary gland development suggests a role in hormone action and epithelial-stromal interactions.

PubMed

Friedmann, Y; Daniel, C W

1996-07-10

The murine homeobox genes Msx-1 and Msx-2 are related to the Drosophila msh gene and are expressed in a variety of tissues during mouse embryogenesis. We now report the developmentally regulated expression of Msx-1 and Msx-2 in the mouse mammary gland and show that their expression patterns point toward significant functional roles. Msx-1 and Msx-2 transcripts were present in glands of virgin mice and in glands of mice in early pregnancy, but transcripts decreased dramatically during late pregnancy. Low levels of Msx-1 transcripts were detected in glands from lactating animals and during the first days of involution, whereas Msx-2 expression was not detected during lactation or early involution. Expression of both genes increased gradually as involution progressed. Msx-2 but not Msx-1 expression was decreased following ovariectomy or following exposure to anti-estrogen implanted directly into the gland. Hormonal regulation of Msx-2 expression was confirmed when transcripts returned to normal levels after estrogen was administered to ovariectomized animals. In situ molecular hybridization for Msx-1 showed transcripts localized to the mammary epithelium, whereas Msx-2 expression was confined to the periductal stroma. Mammary stroma from which mammary epithelium had been removed did not transcribe detectable amounts of Msx-2, showing that expression is regulated by contiguous mammary epithelium, and indicating a role for these homeobox genes in mesenchymal-epithelial interactions during mammary development.

Early postnatal changes in respiratory activity in rat in vitro and modulatory effects of substance P.

PubMed

Shvarev, Y N; Lagercrantz, H

2006-10-01

Developmental changes in the respiratory activity and its modulation by substance P (SP) were studied in the neonatal rat brainstem-spinal cord preparation from the day of birth to day 3 (P0-P3). The respiratory network activity in the ventrolateral medulla was represented by two types of bursts: basic regular bursts with typical decrementing shape and biphasic bursts appearing after augmented biphasic discharges in inspiratory neurons. With advancing postnatal age the respiratory output was considerably modified; the basic rhythm became faster by 20%, whereas the biphasic burst rate, which was originally 15 times slower, declined further by 180% and the C4 burst duration significantly decreased by 20% due to reduced decay time without preceding changes in the central inspiratory drive. SP had an age-dependent excitatory effect on respiratory activity. In the basic rhythm, SP could induce transient rhythm cessations on P0-P2 but not on P3. For the biphasic burst frequency, the sensitivity to SP significantly decreased from P0 to P3, whereas the range of SP-induced changes increased. In both types of bursts, SP prolonged C4 burst duration due to increasing decay time. This effect was three times greater on P3 and did not depend on the central inspiratory drive. Our results suggest that the potency of SP to regulate the respiratory activity elevates during the early postnatal period. The developmental changes in the respiratory activity appear to represent the transient stage in the maturation of rhythm and pattern generation mechanisms facilitating adaptive behavior of a quickly growing organism.

Postnatal treatment with metyrapone attenuates the effects of diet-induced obesity in female rats exposed to early-life stress.

PubMed

Murphy, Margaret O; Herald, Joseph B; Wills, Caleb T; Unfried, Stanley G; Cohn, Dianne M; Loria, Analia S

2017-02-01

Experimental studies in rodents have shown that females are more susceptible to exhibiting fat expansion and metabolic disease compared with males in several models of fetal programming. This study tested the hypothesis that female rat pups exposed to maternal separation (MatSep), a model of early-life stress, display an exacerbated response to diet-induced obesity compared with male rats. Also, we tested whether the postnatal treatment with metyrapone (MTP), a corticosterone synthase inhibitor, would attenuate this phenotype. MatSep was performed in WKY offspring by separation from the dam (3 h/day, postnatal days 2-14). Upon weaning, male and female rats were placed on a normal (ND; 18% kcal fat) or high-fat diet (HFD; 60% kcal fat). Nondisturbed littermates served as controls. In male rats, no diet-induced differences in body weight (BW), glucose tolerance, and fat tissue weight and morphology were found between MatSep and control male rats. However, female MatSep rats displayed increased BW gain, fat pad weights, and glucose intolerance compared with control rats (P < 0.05). Also, HFD increased plasma corticosterone (196 ± 51 vs. 79 ± 18 pg/ml, P < 0.05) and leptin levels (1.8 ± 0.4 vs. 1.3 ± 0.1 ng/ml, P < 0.05) in female MatSep compared with control rats, whereas insulin and adiponectin levels were similar between groups. Female control and MatSep offspring were treated with MTP (50 µg/g ip) 30 min before the daily separation. MTP treatment significantly attenuated diet-induced obesity risk factors, including elevated adiposity, hyperleptinemia, and glucose intolerance. These findings show that exposure to stress hormones during early life could be a key event to enhance diet-induced obesity and metabolic disease in female rats. Thus, pharmacological and/or behavioral inflection of the stress levels is a potential therapeutic approach for prevention of early life stress-enhanced obesity and metabolic disease. Copyright © 2017 the American Physiological

Pseudotemporal Ordering of Single Cells Reveals Metabolic Control of Postnatal β Cell Proliferation.

PubMed

Zeng, Chun; Mulas, Francesca; Sui, Yinghui; Guan, Tiffany; Miller, Nathanael; Tan, Yuliang; Liu, Fenfen; Jin, Wen; Carrano, Andrea C; Huising, Mark O; Shirihai, Orian S; Yeo, Gene W; Sander, Maike

2017-05-02

Pancreatic β cell mass for appropriate blood glucose control is established during early postnatal life. β cell proliferative capacity declines postnatally, but the extrinsic cues and intracellular signals that cause this decline remain unknown. To obtain a high-resolution map of β cell transcriptome dynamics after birth, we generated single-cell RNA-seq data of β cells from multiple postnatal time points and ordered cells based on transcriptional similarity using a new analytical tool. This analysis captured signatures of immature, proliferative β cells and established high expression of amino acid metabolic, mitochondrial, and Srf/Jun/Fos transcription factor genes as their hallmark feature. Experimental validation revealed high metabolic activity in immature β cells and a role for reactive oxygen species and Srf/Jun/Fos transcription factors in driving postnatal β cell proliferation and mass expansion. Our work provides the first high-resolution molecular characterization of state changes in postnatal β cells and paves the way for the identification of novel therapeutic targets to stimulate β cell regeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

Dicer in Mammary Tumor Stem Cell Maintenance

DTIC Science & Technology

2006-03-01

we are cloning small RNAs from mammary stem cells in order to determine the regulatory niches that miRNAs may fill in this cell type. Our ultimate goal is to assess the role of Dicer in mammary tumor stem cell maintenance.

Home-based versus hospital-based postnatal care: a randomised trial.

PubMed

Boulvain, Michel; Perneger, Thomas V; Othenin-Girard, Véronique; Petrou, Stavros; Berner, Michel; Irion, Olivier

2004-08-01

To compare a shortened hospital stay with midwife visits at home to usual hospital care after delivery. Randomised controlled trial. Maternity unit of a Swiss teaching hospital. Four hundred and fifty-nine women with a single uncomplicated pregnancy at low risk of caesarean section. Women were randomised to either home-based (n= 228) or hospital-based postnatal care (n= 231). Home-based postnatal care consisted of early discharge from hospital (24 to 48 hours after delivery) and home visits by a midwife; women in the hospital-based care group were hospitalised for four to five days. Breastfeeding 28 days postpartum, women's views of their care and readmission to hospital. Women in the home-based care group had shorter hospital stays (65 vs 106 hours, P < 0.001) and more midwife visits (4.8 vs 1.7, P < 0.001) than women in the hospital-based care group. Prevalence of breastfeeding at 28 days was similar between the groups (90%vs 87%, P= 0.30), but women in the home-based care group reported fewer problems with breastfeeding and greater satisfaction with the help received. There were no differences in satisfaction with care, women's hospital readmissions, postnatal depression scores and health status scores. A higher percentage of neonates in the home-based care group were readmitted to hospital during the first six months (12%vs 4.8%, P= 0.004). In low risk pregnancies, early discharge from hospital and midwife visits at home after delivery is an acceptable alternative to a longer duration of care in hospital. Mothers' preferences and economic considerations should be taken into account when choosing a policy of postnatal care.

Mammary Hypertrophy in an Ovariohysterectomized Cat

PubMed Central

Pukay, B.P.; Stevenson, D.A.

1983-01-01

A four year old ovariohysterectomized domestic short-haired cat under treatment for behavioral urine spraying and idiopathic alopecia developed mammary gland hypertrophy following treatment with megestrol acetate. Withdrawal of the progestin and treatment with androgen failed to cause regression of the hypertrophy. The affected mammary gland was surgically excised and recovery was uneventful. ImagesFigure 1. PMID:17422254

Postnatal Psychosocial Assessment and Clinical Decision-Making, a Descriptive Study.

PubMed

Sims, Deborah; Fowler, Cathrine

2018-05-18

The aim of this study is to describe experienced child and family health nurses' clinical decision-making during a postnatal psychosocial assessment. Maternal emotional wellbeing in the postnatal year optimises parenting and promotes infant development. Psychosocial assessment potentially enables early intervention and reduces the risk of a mental disorder occurring during this time of change. Assessment accuracy, and the interventions used are determined by the standard of nursing decision-making. A qualitative methodology was employed to explore decision-making behaviour when conducting a postnatal psychosocial assessment. This study was conducted in an Australian early parenting organisation. Twelve experienced child and family health nurses were interviewed. A detailed description of a postnatal psychosocial assessment process was obtained using a critical incident technique. Template analysis was used to determine the information domains the nurses accessed, and content analysis was used to determine the nurses' thinking strategies, to make clinical decisions from this assessment. The nurses described 24 domains of information and used 17 thinking strategies, in a variety of combinations. The four information domains most commonly used were parenting, assessment tools, women-determined issues and sleep. The seven thinking strategies most commonly used were searching for information, forming relationships between the information, recognising a pattern, drawing a conclusion, setting priorities, providing explanations for the information and judging the value of the information. The variety and complexity of the clinical decision-making involved in postnatal psychosocial assessment confirms that the nurses use information appropriately and within their scope of nursing practice. The standard of clinical decision-making determines the results of the assessment and the optimal access to care. Knowledge of the information domains and the decision-making strategies

The spectrum of STAT functions in mammary gland development

PubMed Central

Hughes, Katherine; Watson, Christine J.

2012-01-01

The signal transducer and activator of transcription (STAT) family of transcription factors have a spectrum of functions in mammary gland development. In some cases these roles parallel those of STATs in other organ systems, while in other instances the function of individual STATs in the mammary gland is specific to this tissue. In the immune system, STAT6 is associated with differentiation of T helper cells, while in the mammary gland, it has a fundamental role in the commitment of luminal epithelial cells to the alveolar lineage. STAT5A is required for the production of luminal progenitor cells from mammary stem cells and is essential for the differentiation of milk producing alveolar cells during pregnancy. By contrast, the initiation of regression following weaning heralds a dramatic and specific activation of STAT3, reflecting its pivotal role in the regulation of cell death and tissue remodeling during mammary involution. Although it has been demonstrated that STAT1 is regulated during a mammary developmental cycle, it is not yet determined whether it has a specific, non-redundant function. Thus, the mammary gland constitutes an unusual example of an adult organ in which different STATs are sequentially activated to orchestrate the processes of functional differentiation, cell death and tissue remodeling. PMID:24058764

Fetal alcohol exposure and mammary tumorigenesis in offspring: role of the estrogen and insulin-like growth factor systems.

PubMed

Cohick, Wendie S; Crismale-Gann, Catina; Stires, Hillary; Katz, Tiffany A

2015-01-01

Fetal alcohol spectrum disorders affect a significant number of live births each year, indicating that alcohol consumption during pregnancy is an important public health issue. Environmental exposures and lifestyle choices during pregnancy may affect the offspring's risk of disease in adulthood, leading to the idea that a woman's risk of breast cancer may be pre-programmed prior to birth. Exposure of pregnant rats to alcohol increases tumorigenesis in the adult offspring in response to mammary carcinogens. The estrogen and insulin-like growth factor (IGF-I) axes occupy central roles in normal mammary gland development and breast cancer. 17-β estradiol (E2) and IGF-I synergize to regulate formation of terminal end buds and ductal elongation during pubertal development. The intracellular signaling pathways mediated by the estrogen and IGF-I receptors cross-talk at multiple levels through both genomic and non-genomic mechanisms. Several components of the E2 and IGF-I systems are altered in early development in rat offspring exposed to alcohol in utero, therefore, these changes may play a role in the enhanced susceptibility to mammary carcinogens observed in adulthood. Alcohol exposure in utero induces a number of epigenetic alterations in non-mammary tissues in the offspring and other adverse in utero exposures induce epigenetic modifications in the mammary gland. Future studies will determine if fetal alcohol exposure can induce epigenetic modifications in genes that regulate E2/IGF action at key phases of mammary development, ultimately leading to changes in susceptibility to carcinogens.

Early postnatal exposure to methylphenidate alters stress reactivity and increases hippocampal ectopic granule cells in adult rats

PubMed Central

Torres-Reveron, Annelyn; Gray, Jason D.; Melton, Jay T.; Punsoni, Michael; Tabori, Nora E.; Ward, Mary J.; Frys, Kelly; Iadecola, Costantino; Milner, Teresa A.

2009-01-01

To mimic clinical treatment with methylphenidate (MPH; Ritalin) for attention deficit/hyperactivity disorder (ADHD), rat pups were injected with MPH (5 mg/kg, I.P.) or placebo twice daily during their nocturnal active phase from postnatal day (PND) 7 to 35. Thirty-nine days after the last MPH administration (PND76), four litters of rats experienced stressful conditions during the 2003 New York City blackout. MPH-treated rats that endured the blackout lost more weight and regained it at a slower pace than controls (p<0.05; N=7–11/group). Furthermore, MPH-treated rats had elevated systolic arterial blood pressure (from 115.6 ± 1.2 to 126 ± 1.8 mmHg; p<0.05), assessed on PND130 by tail cuff plethysmography. Immunocytochemical studies of transmitter systems in the brain demonstrated rearrangements of catecholamine and neuropeptide Y fibers in select brain regions at PND135, which did not differ between blackout and control groups. However, MPH-treated rats that endured the blackout had more ectopic granule cells in the hilus of the dorsal hippocampal dentate gyrus compared to controls at PND 135 (p<0.05; N=6/group). These findings indicate that early postnatal exposure to high therapeutic doses of MPH can have long lasting effects on the plasticity of select brain regions and can induce changes in the reactivity to stress that persist into adulthood. PMID:19100815

The mouse mammary gland as a sentinel organ: distinguishing 'control' populations with diverse environmental histories.

PubMed

Kolla, SriDurgaDevi; Pokharel, Aastha; Vandenberg, Laura N

2017-03-09

There are numerous examples of laboratory animals that were inadvertently exposed to endocrine disrupting chemicals (EDCs) during the process of conducting experiments. Controlling contaminations in the laboratory is challenging, especially when their source is unknown. Unfortunately, EDC contaminations can interfere with the interpretation of data during toxicological evaluations. We propose that the male CD-1 mouse mammary gland is a sensitive bioassay to evaluate the inadvertent contamination of animal colonies. We evaluated mammary glands collected from two CD-1 mouse populations with distinct environmental histories. Population 1 was born and raised in a commercial laboratory with unknown EDC exposures; Population 2 was the second generation raised in an animal facility with limited exposures to xenoestrogens from caging, feed, etc. Mammary glands were collected from all animals and evaluated using morphometric techniques to quantify morphological characteristics of the mammary gland. Population 1 (with suspected history of environmental chemical exposure) and Population 2 (with known limited history of xenoestrogen exposure) were morphologically distinguishable in adult males, prepubertal females, and pubertal females. Mammary glands from males raised in the commercial animal facility were significantly more developed, with larger ductal trees and more branching points. The appearance of these mammary glands was consistent with prior reports of male mice exposed to low doses of bisphenol A (BPA) during early development. In females, the two populations were morphologically distinct at both prepuberty and puberty, with the most striking differences observed in the number, size, and density of terminal end buds, e.g. highly proliferative structures found in the developing mammary gland. Collectively, these results suggest that the mouse mammary gland has the potential to be used as a sentinel organ to evaluate and distinguish animal colonies raised in different

Cutaneous metastases of a mammary carcinoma in a llama.

PubMed Central

Leichner, T L; Turner, O; Mason, G L; Barrington, G M

2001-01-01

An 8-year-old, female llama was evaluated for nonhealing, ulcerative, cutaneous lesions, which also involved the mammary gland. Biopsies of the lesions distant from and within the mammary gland area revealed an aggressive carcinoma. The tumor was confirmed at necropsy to be a mammary gland adenocarcinoma with cutaneous metastasis. Images Figure 1. PMID:11265189

Targeted surveillance for postnatal hearing loss: a program evaluation.

PubMed

Beswick, Rachael; Driscoll, Carlie; Kei, Joseph; Glennon, Shirley

2012-07-01

The importance of monitoring hearing throughout early childhood cannot be understated. However, there is a lack of evidence available regarding the most effective method of monitoring hearing following the newborn screen. The goal of this study was to describe a targeted surveillance program using a risk factor registry to identify children with a postnatal hearing loss. All children who were born in Queensland, Australia between September 2004 and December 2009, received a bilateral 'pass' on newborn hearing screening, and had at least one risk factor, were referred for targeted surveillance and were included in this study. The cohort was assessed throughout early childhood in accordance with Queensland's diagnostic assessment protocols. During the study period, 7320 (2.8% of 261,328) children were referred for targeted surveillance, of which 56 were identified with a postnatal hearing loss (0.77%). Of these, half (50.0%) were identified with a mild hearing loss, and 64.3% were identified with a sensorineural hearing loss. In regards to risk factors, syndrome, craniofacial anomalies, and severe asphyxia had the highest yield of positive cases of postnatal hearing loss for children referred for targeted surveillance, whereas, low birth weight, bacterial meningitis, and professional concern had a particularly low yield. Limitations of the targeted surveillance program were noted and include: (1) a lost contact rate of 32.4%; (2) delays in first surveillance assessment; (3) a large number of children who required on-going monitoring; and (4) extensive diagnostic assessments were completed on children with normal hearing. Examination of the lost contact rate revealed indigenous children were more likely to be documented as lost contact. In addition, children with one risk factor only were significantly more likely to not attend a surveillance appointment. Positive cases of postnatal hearing loss were detected through the targeted surveillance program. However, the

PROLACTIN REGULATES LIVER GROWTH DURING POSTNATAL DEVELOPMENT IN MICE.

PubMed

Moreno-Carranza, Bibiana; Bravo-Manríquez, Marco; Baez, Arelí; Ledesma-Colunga, María G; Ruiz-Herrera, Xarubet; Reyes-Ortega, Pamela; De Los Ríos, Ericka A; Macotela, Yazmín; Martínez de la Escalera, Gonzalo; Clapp, Carmen

2018-02-21

The liver grows during the early postnatal period first at slower and then at faster rates than the body to achieve the adult liver-to-body weight ratio (LBW), a constant reflecting liver health. The hormone prolactin (PRL) stimulates adult liver growth and regeneration and its levels are high in the circulation of newborn infants, but whether PRL plays a role on neonatal liver growth is unknown. Here, we show that the liver produces PRL and upregulates the PRL receptor in mice during the first 2 weeks after birth, when liver growth lags behind body growth. At postnatal week 4, the production of PRL by the liver ceases coinciding with the elevation of circulating PRL and the faster liver growth that catches up with body growth. PRL receptor null mice (Prlr-/-) show a significant decrease in the LBW at 1, 4, 6, and 10 postnatal weeks and reduced liver expression of proliferation (cyclin D1, Ccnd1) and angiogenesis (platelet/endothelial cell adhesion molecule 1, Pecam1) markers relative to Prlr+/+ mice. However, the LBW increases in Prlr-/- mice at postnatal week 2 concurring with the enhanced liver expression of Igf-1 and the liver upregulation and downregulation of suppressor of cytokine signaling 2 (Socs2) and Socs3, respectively. These findings indicate that PRL acts locally and systemically to restrict and stimulate postnatal liver growth. PRL inhibits liver and body growth by attenuating growth hormone-induced Igf-1 liver expression via Socs2 and Socs3-related mechanisms.

Macrophage-Mediated Glial Cell Elimination in the Postnatal Mouse Cochlea

PubMed Central

Brown, LaShardai N.; Xing, Yazhi; Noble, Kenyaria V.; Barth, Jeremy L.; Panganiban, Clarisse H.; Smythe, Nancy M.; Bridges, Mary C.; Zhu, Juhong; Lang, Hainan

2017-01-01

Hearing relies on the transmission of auditory information from sensory hair cells (HCs) to the brain through the auditory nerve. This relay of information requires HCs to be innervated by spiral ganglion neurons (SGNs) in an exclusive manner and SGNs to be ensheathed by myelinating and non-myelinating glial cells. In the developing auditory nerve, mistargeted SGN axons are retracted or pruned and excessive cells are cleared in a process referred to as nerve refinement. Whether auditory glial cells are eliminated during auditory nerve refinement is unknown. Using early postnatal mice of either sex, we show that glial cell numbers decrease after the first postnatal week, corresponding temporally with nerve refinement in the developing auditory nerve. Additionally, expression of immune-related genes was upregulated and macrophage numbers increase in a manner coinciding with the reduction of glial cell numbers. Transient depletion of macrophages during early auditory nerve development, using transgenic CD11bDTR/EGFP mice, resulted in the appearance of excessive glial cells. Macrophage depletion caused abnormalities in myelin formation and transient edema of the stria vascularis. Macrophage-depleted mice also showed auditory function impairment that partially recovered in adulthood. These findings demonstrate that macrophages contribute to the regulation of glial cell number during postnatal development of the cochlea and that glial cells play a critical role in hearing onset and auditory nerve maturation. PMID:29375297

Supplementation with fish oil and coconut fat prevents prenatal stress-induced changes in early postnatal development.

PubMed

Borsonelo, Elizabethe C; Suchecki, Deborah; Calil, Helena Maria; Galduróz, José Carlos F

2011-08-01

Adequate development of the central nervous system depends on prenatal and postnatal factors. On one hand, prenatal stress (PNS) has been implicated in impaired development of the offspring. On other hand, nutritional factors during pregnancy and lactation can influence fetal and postnatal growth. This study assessed the postnatal development of rat offspring exposed to PNS, which consisted of restraint and bright lights, 3 times/day, from days 14 to 20 of pregnancy, whose mothers were fed different diets during pregnancy and lactation: regular diet, diet supplemented with coconut fat or fish oil. When pregnancy was confirmed, they were distributed into control (CTL) or PNS groups. At birth, PNS males and females weighed less than those in the group CTL. At 21 days of age, this alteration was no longer observed with fish oil and coconut fat groups. PNS and coconut fat diet induced increased locomotor activity in 13 day old male and female pups, and this effect was prevented by fish oil supplementation only in females. In conclusion, postnatal development from birth to weaning was influenced by PNS and diet and some of those alterations were prevented by coconut fat and fish oil. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

Runx2 contributes to the regenerative potential of the mammary epithelium.

PubMed

Ferrari, Nicola; Riggio, Alessandra I; Mason, Susan; McDonald, Laura; King, Ayala; Higgins, Theresa; Rosewell, Ian; Neil, James C; Smalley, Matthew J; Sansom, Owen J; Morris, Joanna; Cameron, Ewan R; Blyth, Karen

2015-10-22

Although best known for its role in bone development and associated structures the transcription factor RUNX2 is expressed in a wide range of lineages, including those of the mammary gland. Previous studies have indicated that Runx2 can regulate aspects of mammary cell function and influence the properties of cancer cells. In this study we investigate the role of Runx2 in the mammary stem/progenitor population and its relationship with WNT signalling. Results show that RUNX2 protein is differentially expressed throughout embryonic and adult development of the murine mammary gland with high levels of expression in mammary stem-cell enriched cultures. Importantly, functional analysis reveals a role for Runx2 in mammary stem/progenitor cell function in in vitro and in vivo regenerative assays. Furthermore, RUNX2 appears to be associated with WNT signalling in the mammary epithelium and is specifically upregulated in mouse models of WNT-driven breast cancer. Overall our studies reveal a novel function for Runx2 in regulating mammary epithelial cell regenerative potential, possibly acting as a downstream target of WNT signalling.

Runx2 contributes to the regenerative potential of the mammary epithelium

PubMed Central

Ferrari, Nicola; Riggio, Alessandra I.; Mason, Susan; McDonald, Laura; King, Ayala; Higgins, Theresa; Rosewell, Ian; Neil, James C.; Smalley, Matthew J.; Sansom, Owen J.; Morris, Joanna; Cameron, Ewan R.; Blyth, Karen

2015-01-01

Although best known for its role in bone development and associated structures the transcription factor RUNX2 is expressed in a wide range of lineages, including those of the mammary gland. Previous studies have indicated that Runx2 can regulate aspects of mammary cell function and influence the properties of cancer cells. In this study we investigate the role of Runx2 in the mammary stem/progenitor population and its relationship with WNT signalling. Results show that RUNX2 protein is differentially expressed throughout embryonic and adult development of the murine mammary gland with high levels of expression in mammary stem-cell enriched cultures. Importantly, functional analysis reveals a role for Runx2 in mammary stem/progenitor cell function in in vitro and in vivo regenerative assays. Furthermore, RUNX2 appears to be associated with WNT signalling in the mammary epithelium and is specifically upregulated in mouse models of WNT-driven breast cancer. Overall our studies reveal a novel function for Runx2 in regulating mammary epithelial cell regenerative potential, possibly acting as a downstream target of WNT signalling. PMID:26489514

Mammary gland-specific nuclear factor activity is positively regulated by lactogenic hormones and negatively by milk stasis.

PubMed

Schmitt-Ney, M; Happ, B; Hofer, P; Hynes, N E; Groner, B

1992-12-01

The mammary gland-specific nuclear factor (MGF) is a crucial contributor to the regulation of transcription from the beta-casein gene promoter. The beta-casein gene encodes a major milk protein, which is expressed in mammary epithelial cells during lactation and can be induced by lactogenic hormones in the clonal mammary epithelial cell line HC11. We have investigated the specific DNA-binding activity of MGF in mammary epithelial cells in vivo and in vitro. Comparison of MGF in HC11 cells and mammary gland cells from lactating mice revealed molecules with identical DNA-binding properties. Bandshift and UV cross-linking experiments indicated that MGF in HC11 cells has a higher mol wt than MGF found in mice. Little MGF activity was detected in nuclear extracts from HC11 cells cultured in the absence of lactogenic hormones. Lactogenic hormone treatment of HC11 cells led to a strong induction of MGF activity. The induction of MGF activity as well as utilization of the beta-casein promoter were suppressed when epidermal growth factor was present in the tissue culture medium simultaneously with the lactogenic hormones. In lactating animals, MGF activity is regulated by suckling, milk stasis, and systemic hormone signals. The mammary glands from maximally lactating animals, 16 days postpartum, contain drastically reduced MGF activity after removal of the pups for only 8 h. The down-regulation of MGF by pup withdrawal was slower in early lactation, 6 days postpartum. We also investigated the relative contributions of local signals, generated by milk stasis, and systemic hormone signals to the regulation of MGF activity. The access to one row of mammary glands of lactating mothers was denied to the pups for 24 h. High levels of MGF were found in the accessible mammary glands, and intermediate levels of MGF were found in the inaccessible glands of the same mouse. Very low MGF levels were detected when the pups were removed from the dams for 24 h. We conclude that systemic as

Duodenal Ca2+ absorption is not stimulated by calcitriol during early postnatal development of pigs.

PubMed

Schroeder, B; Dahl, M R; Breves, G

1998-08-01

The role of calcitriol in stimulating intestinal active Ca2+ absorption during postnatal life was studied in newborn, suckling, and weaned control (Con) piglets and piglets suffering from inherited calcitriol deficiency (Def piglets). In addition, a group of Def piglets was treated with vitamin D3 (Def-D3 piglets), which normalized plasma calcitriol levels. Regardless of age, duodenal calbindin-D9k concentrations ranged between 1,839 and 2,846 microg/g mucosa in Con piglets, between 821 and 1,219 microg/g mucosa in Def piglets, and between 2,960 and 3,692 microg/g mucosa in Def-D3 animals. In weaned animals, active Ca2+ absorption as calculated from in vitro 45Ca2+ flux rate measurements in Ussing chambers could be related to calbindin-D9k levels. Thus active Ca2+ absorption was completely absent in Def animals but was reconstituted in Def-D3 animals. In contrast, in newborn Def piglets active Ca2+ absorption functioned normally despite the low plasma calcitriol and mucosal calbindin-D9k levels and could not be affected by treatment with vitamin D3. Similar results were obtained from suckling Def piglets. The microtubule-disrupting agent colchicine caused significant inhibition of transepithelial net Ca2+ absorption in duodenal epithelia from newborn piglets without exerting an effect in suckling and weaned animals. Colchicine had no effect on Ca2+ uptake across the brush border membrane of mucosal enterocytes or on glucose-dependent electrogenic net ion flux rates in duodenal preparations from newborn Con piglets. In conclusion, our findings reveal intestinal active Ca2+ absorption during early postnatal life of pigs that involves calcitriol-independent mechanisms and that may include intact microtubule actions.

Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miki, Takanori, E-mail: mikit@med.kagawa-u.ac.jp; Liu, Jun-Qian; Ohta, Ken-ichi

Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved bymore » separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.« less

Mammary Duct Ectasia

MedlinePlus

... tenderness or inflammation of the clogged duct (periductal mastitis). Mammary duct ectasia most often occurs in women ... that's turned inward (inverted) A bacterial infection called mastitis also may develop in the affected milk duct, ...

Parity-induced decrease in systemic growth hormone alters mammary gland signaling: A potential role in pregnancy protection from breast cancer

PubMed Central

Dearth, Robert K.; Delgado, David A.; Hiney, Jill K; Pathiraja, Thushangi; Oesterreich, Steffi; Medina, Dan; Dees, W. Les; Lee, Adrian V.

2009-01-01

Early full-term pregnancy is an effective natural protection against breast cancer in both humans and experimental rodents. The protective effect of an early pregnancy is in part linked to changes in circulating hormones that are involved in both normal breast development and breast cancer. For example, a reduction in circulating growth hormone (GH) has been shown to protect rats from carcinogen-induced mammary tumors. We examined the ability of a full-term pregnancy to alter the endocrine GH/IGF-I axis and how this change affected normal mammary gland function in two commonly used rat models (Sprague-Dawley and Wistar-Furth). Circulating GH and IGF-I were measured in blood drawn every 30 minutes from parous and aged-matched virgin (AMV) female rats. Mean serum GH levels were significantly decreased (p<0.01) in parous compared to AMV in both rat strains. Changes in GH levels were independent of estrous cycle, indicated by a significant (p<0.05) reduction in circulating levels of GH during estrus and diestrus in both parous strains. Despite the decrease in circulating GH, pituitary GH mRNA levels were unaltered in parous rats. Circulating IGF-I and hepatic IGF-I mRNA were also unaltered by parity in either rat strain. Immunoblot analysis of mammary glands showed decreases in phosphorylation of Stat5A and Jak2, suggesting reduced action of GH in the mammary gland. Therefore, while the parity reduction in circulating GH doesn’t impact upon circulating IGF-I levels, it is possible that reduced GH action directly at the mammary gland and may play a role in pregnancy protection from breast cancer. PMID:20145191

Preparing and Analyzing Expressed Sequence Tags (ESTs) Library for the Mammary Tissue of Local Turkish Kivircik Sheep

PubMed Central

Omeroglu Ulu, Zehra; Ulu, Salih; Un, Cemal; Ozdem Oztabak, Kemal; Altunatmaz, Kemal

2017-01-01

Kivircik sheep is an important local Turkish sheep according to its meat quality and milk productivity. The aim of this study was to analyze gene expression profiles of both prenatal and postnatal stages for the Kivircik sheep. Therefore, two different cDNA libraries, which were taken from the same Kivircik sheep mammary gland tissue at prenatal and postnatal stages, were constructed. Total 3072 colonies which were randomly selected from the two libraries were sequenced for developing a sheep ESTs collection. We used Phred/Phrap computer programs for analysis of the raw EST and readable EST sequences were assembled with the CAP3 software. Putative functions of all unique sequences and statistical analysis were determined by Geneious software. Total 422 ESTs have over 80% similarity to known sequences of other organisms in NCBI classified by Panther database for the Gene Ontology (GO) category. By comparing gene expression profiles, we observed some putative genes that may be relative to reproductive performance or play important roles in milk synthesis and secretion. A total of 2414 ESTs have been deposited to the NCBI GenBank database (GW996847–GW999260). EST data in this study have provided a new source of information to functional genome studies of sheep. PMID:28239610

The male mammary gland: a target for the xenoestrogen bisphenol A

PubMed Central

Vandenberg, Laura N; Schaeberle, Cheryl M.; Rubin, Beverly S.; Sonnenschein, Carlos; Soto, Ana M.

2014-01-01

Males of some strains of mice retain their mammary epithelium even in the absence of nipples. Here, we have characterized the mammary gland in male CD-1 mice both in whole mounts and histological sections. We also examined the effects of bisphenol A (BPA), an estrogen mimic that alters development of the female mouse mammary gland. BPA was administered at a range of environmentally relevant doses (0.25 – 250 μg/kg/day) to pregnant and lactating mice and then the mammary glands of male offspring were examined at several periods in adulthood. We observed age- and dose-specific effects on mammary gland morphology, indicating that perinatal BPA exposures alter the male mammary gland in adulthood. These results may provide insight into gynecomastia, the most common male breast disease in humans, where proliferation of the mammary epithelium leads to breast enlargement. PMID:23348055

Sequencing the transcriptome of milk production: milk trumps mammary tissue

PubMed Central

2013-01-01

Background Studies of normal human mammary gland development and function have mostly relied on cell culture, limited surgical specimens, and rodent models. Although RNA extracted from human milk has been used to assay the mammary transcriptome non-invasively, this assay has not been adequately validated in primates. Thus, the objectives of the current study were to assess the suitability of lactating rhesus macaques as a model for lactating humans and to determine whether RNA extracted from milk fractions is representative of RNA extracted from mammary tissue for the purpose of studying the transcriptome of milk-producing cells. Results We confirmed that macaque milk contains cytoplasmic crescents and that ample high-quality RNA can be obtained for sequencing. Using RNA sequencing, RNA extracted from macaque milk fat and milk cell fractions more accurately represented RNA from mammary epithelial cells (cells that produce milk) than did RNA from whole mammary tissue. Mammary epithelium-specific transcripts were more abundant in macaque milk fat, whereas adipose or stroma-specific transcripts were more abundant in mammary tissue. Functional analyses confirmed the validity of milk as a source of RNA from milk-producing mammary epithelial cells. Conclusions RNA extracted from the milk fat during lactation accurately portrayed the RNA profile of milk-producing mammary epithelial cells in a non-human primate. However, this sample type clearly requires protocols that minimize RNA degradation. Overall, we validated the use of RNA extracted from human and macaque milk and provided evidence to support the use of lactating macaques as a model for human lactation. PMID:24330573

Sequencing the transcriptome of milk production: milk trumps mammary tissue.

PubMed

Lemay, Danielle G; Hovey, Russell C; Hartono, Stella R; Hinde, Katie; Smilowitz, Jennifer T; Ventimiglia, Frank; Schmidt, Kimberli A; Lee, Joyce W S; Islas-Trejo, Alma; Silva, Pedro Ivo; Korf, Ian; Medrano, Juan F; Barry, Peter A; German, J Bruce

2013-12-12

Studies of normal human mammary gland development and function have mostly relied on cell culture, limited surgical specimens, and rodent models. Although RNA extracted from human milk has been used to assay the mammary transcriptome non-invasively, this assay has not been adequately validated in primates. Thus, the objectives of the current study were to assess the suitability of lactating rhesus macaques as a model for lactating humans and to determine whether RNA extracted from milk fractions is representative of RNA extracted from mammary tissue for the purpose of studying the transcriptome of milk-producing cells. We confirmed that macaque milk contains cytoplasmic crescents and that ample high-quality RNA can be obtained for sequencing. Using RNA sequencing, RNA extracted from macaque milk fat and milk cell fractions more accurately represented RNA from mammary epithelial cells (cells that produce milk) than did RNA from whole mammary tissue. Mammary epithelium-specific transcripts were more abundant in macaque milk fat, whereas adipose or stroma-specific transcripts were more abundant in mammary tissue. Functional analyses confirmed the validity of milk as a source of RNA from milk-producing mammary epithelial cells. RNA extracted from the milk fat during lactation accurately portrayed the RNA profile of milk-producing mammary epithelial cells in a non-human primate. However, this sample type clearly requires protocols that minimize RNA degradation. Overall, we validated the use of RNA extracted from human and macaque milk and provided evidence to support the use of lactating macaques as a model for human lactation.

Birth weight and postnatal growth in preterm born children are associated with cortisol in early infancy, but not at age 8 years.

PubMed

Ruys, Charlotte A; van der Voorn, Bibian; Lafeber, Harrie N; van de Lagemaat, Monique; Rotteveel, Joost; Finken, Martijn J J

2017-08-01

Preterm birth has been associated with altered hypothalamic-pituitary-adrenal (HPA-) axis activity as well as cardiometabolic diseases and neurodevelopmental impairments later in life. We assessed cortisol from term age to age 8 y in children born preterm, to explore the development of HPA-axis activity in association with intrauterine and early-postnatal growth until 6 mo. corrected age. In 152 children born at a gestational age ≤32 wks. and/or with a birth weight ≤1,500g, random serum cortisol was assessed at term age (n=150), 3 mo. (n=145) and 6 mo. corrected age (n=144), and age 8 y (n=59). Salivary cortisol was assessed at age 8 y (n=75): prior to bedtime, at awakening, 15min after awakening, and before lunch. Cortisol was analyzed in association with birth weight-standard deviation score (SDS), being born small for gestational age (SGA), and combinations of intrauterine and postnatal growth: appropriate for gestational age (AGA) with or without growth restriction (AGA GR+ or AGA GR-) at 6 mo. corrected age, and SGA with or without catch-up growth (SGA CUG+ or SGA CUG-) at 6 mo. corrected age. Cross-sectional associations at all time points were analyzed using linear regression, and longitudinal associations were analyzed using generalized estimating equations. Longitudinally, birth weight-SDS was associated with cortisol (β [95%CI]): lower cortisol over time was seen in infants with a birth weight ≤-2 SDS (-50.69 [-94.27; -7.11], p=0.02), infants born SGA (-29.70 [-60.58; 1.19], p=0.06), AGA GR+ infants (-55.10 [-106.02; -4.17], p=0.03) and SGA CUG- infants (-61.91 [-104.73; -19.10], p=0.01). In cross-sectional analyses at age 8 y, no associations were found between either serum or salivary cortisol and birth weight-SDS, SGA-status, or growth from birth to 6 mo. corrected age. In children born preterm, poor intrauterine and postnatal growth were associated with lower cortisol in early infancy, but not at age 8 y. Even though HPA-axis activity no longer

Scribble Modulates the MAPK/Fra1 Pathway to Disrupt Luminal and Ductal Integrity and Suppress Tumour Formation in the Mammary Gland

PubMed Central

Godde, Nathan J.; Sheridan, Julie M.; Smith, Lorey K.; Pearson, Helen B.; Britt, Kara L.; Galea, Ryan C.; Yates, Laura L.; Visvader, Jane E.; Humbert, Patrick O.

2014-01-01

Polarity coordinates cell movement, differentiation, proliferation and apoptosis to build and maintain complex epithelial tissues such as the mammary gland. Loss of polarity and the deregulation of these processes are critical events in malignant progression but precisely how and at which stage polarity loss impacts on mammary development and tumourigenesis is unclear. Scrib is a core polarity regulator and tumour suppressor gene however to date our understanding of Scrib function in the mammary gland has been limited to cell culture and transplantation studies of cell lines. Utilizing a conditional mouse model of Scrib loss we report for the first time that Scrib is essential for mammary duct morphogenesis, mammary progenitor cell fate and maintenance, and we demonstrate a critical and specific role for Scribble in the control of the early steps of breast cancer progression. In particular, Scrib-deficiency significantly induced Fra1 expression and basal progenitor clonogenicity, which resulted in fully penetrant ductal hyperplasia characterized by high cell turnover, MAPK hyperactivity, frank polarity loss with mixing of apical and basolateral membrane constituents and expansion of atypical luminal cells. We also show for the first time a role for Scribble in mammalian spindle orientation with the onset of mammary hyperplasia being associated with aberrant luminal cell spindle orientation and a failure to apoptose during the final stage of duct tubulogenesis. Restoring MAPK/Fra1 to baseline levels prevented Scrib-hyperplasia, whereas persistent Scrib deficiency induced alveolar hyperplasia and increased the incidence, onset and grade of mammary tumours. These findings, based on a definitive genetic mouse model provide fundamental insights into mammary duct maturation and homeostasis and reveal that Scrib loss activates a MAPK/Fra1 pathway that alters mammary progenitor activity to drive premalignancy and accelerate tumour progression. PMID:24852022

Mammary gland tumors in captive African hedgehogs.

PubMed

Raymond, J T; Gerner, M

2000-04-01

From December 1995 to July 1999, eight mammary gland tumors were diagnosed in eight adult captive female African hedgehogs (Atelerix albiventris). The tumors presented as single or multiple subcutaneous masses along the cranial or caudal abdomen that varied in size for each hedgehog. Histologically, seven of eight (88%) mammary gland tumors were malignant. Tumors were classified as solid (4 cases), tubular (2 cases), and papillary (2 cases). Seven tumors had infiltrated into the surrounding stroma and three tumors had histologic evidence of neoplastic vascular invasion. Three hedgehogs had concurrent neoplasms. These are believed to be the first reported cases of mammary gland tumors in African hedgehogs.

Food, growth and time: Elsie Widdowson's and Robert McCance's research into prenatal and early postnatal growth.

PubMed

Buklijas, Tatjana

2014-09-01

Cambridge scientists Robert McCance and Elsie Widdowson are best known for their work on the British food tables and wartime food rations, but it is their research on prenatal and early postnatal growth that is today seen as a foundation of the fields studying the impact of environment upon prenatal development and, consequently, adult disease. In this essay I situate McCance's and Widdowson's 1940s human and 1950s experimental studies in the context of pre-war concerns with fetal growth and development, especially within biochemistry, physiology and agriculture; and the Second World War and post-war focus on the effects of undernutrition during pregnancy upon the fetus. I relate Widdowson's and McCance's research on the long-term effects of early undernutrition to the concern with recovery from early trauma so pertinent in post-war Europe and with sensitive (critical) periods, a concept of high importance across different fields. Finally I discuss how, following a hiatus in which fetal physiology engaged with different questions and stressed fetal autonomy, interest in the impact of environment upon prenatal growth and development revived towards the end of the twentieth century. The new field of "developmental origins of health and disease", I suggest, has provided a context in which Widdowson's and McCance's work has regained importance. Copyright © 2013 Elsevier Ltd. All rights reserved.

A novel approach for the generation of genetically modified mammary epithelial cell cultures yields new insights into TGFβ signaling in the mammary gland

PubMed Central

2010-01-01

Introduction Molecular dissection of the signaling pathways that underlie complex biological responses in the mammary epithelium is limited by the difficulty of propagating large numbers of mouse mammary epithelial cells, and by the inability of ribonucleic acid interference-based knockdown approaches to fully ablate gene function. Here we describe a method for the generation of conditionally immortalized mammary epithelial cells with defined genetic defects, and we show how such cells can be used to investigate complex signal transduction processes using the transforming growth factor beta (TGFβ)/Smad pathway as an example. Methods We intercrossed the previously described H-2Kb-tsA58 transgenic mouse (Immortomouse), which expresses a temperature-sensitive mutant of the simian virus-40 large T-antigen (tsTAg), with mice of differing Smad genotypes. Conditionally immortalized mammary epithelial cell cultures were derived from the virgin mammary glands of offspring of these crosses and were used to assess the Smad dependency of different biological responses to TGFβ. Results IMECs could be propagated indefinitely at permissive temperatures and had a stable epithelial phenotype, resembling primary mammary epithelial cells with respect to several criteria, including responsiveness to TGFβ. Using this panel of cells, we demonstrated that Smad3, but not Smad2, is necessary for TGFβ-induced apoptotic, growth inhibitory and epithelial-to-mesenchymal transition responses, whereas either Smad2 or Smad3 can support TGFβ-induced invasion as long as a threshold level of total Smad is exceeded. Conclusions The present work demonstrates the practicality and utility of generating conditionally immortalized mammary epithelial cell lines from genetically modified Immortomice for detailed investigation of complex signaling pathways in the mammary epithelium. PMID:20942910

Lack of the alanine-serine-cysteine transporter 1 causes tremors, seizures, and early postnatal death in mice.

PubMed

Xie, Xinmin; Dumas, Theodore; Tang, Lamont; Brennan, Thomas; Reeder, Thadd; Thomas, Winston; Klein, Robert D; Flores, Judith; O'Hara, Bruce F; Heller, H Craig; Franken, Paul

2005-08-09

The Na(+)-independent alanine-serine-cysteine transporter 1 (Asc-1) is exclusively expressed in neuronal structures throughout the central nervous system (CNS). Asc-1 transports small neutral amino acids with high affinity especially for D-serine and glycine (K(i): 8-12 microM), two endogenous glutamate co-agonists that activate N-methyl-D-aspartate (NMDA) receptors through interacting with the strychnine-insensitive glycine binding-site. By regulating D-serine (and possibly glycine) levels in the synaptic cleft, Asc-1 may play an important role in controlling neuronal excitability. We generated asc-1 gene knockout (asc-1(-/-)) mice to test this hypothesis. Behavioral phenotyping combined with electroencephalogram (EEG) recordings revealed that asc-1(-/-) mice developed tremors, ataxia, and seizures that resulted in early postnatal death. Both tremors and seizures were reduced by the NMDA receptor antagonist MK-801. Extracellular recordings from asc-1(-/-) brain slices indicated that the spontaneous seizure activity did not originate in the hippocampus, although, in this region, a relative increase in evoked synaptic responses was observed under nominal Mg(2+)-free conditions. Taken together with the known neurochemistry and neuronal distribution of the Asc-1 transporter, these results indicate that the mechanism underlying the behavioral hyperexcitability in mutant mice is likely due to overactivation of NMDA receptors, presumably resulting from elevated extracellular D-serine. Our study provides the first evidence to support the notion that Asc-1 transporter plays a critical role in regulating neuronal excitability, and indicate that the transporter is vital for normal CNS function and essential to postnatal survival of mice.

Mammary microbiota of dairy ruminants: fact or fiction?

PubMed

Rainard, Pascal

2017-04-17

Explorations of how the complex microbial communities that inhabit different body sites might contribute to health and disease have prompted research on the ways the harmonious relationship between a host and its microbiota could be used to keep animals healthy in their production conditions. In particular, there is a growing interest in the bacterial signatures that can be found in the milk of healthy or mastitic dairy cows. The concept of sterility of the healthy mammary gland of dairy ruminants has been challenged by the results of studies using bacterial DNA-based methodology. The newly obtained data have led to the concept of the intramammary microbiota composed of a complex community of diverse bacteria. Accordingly, mammary gland infections are not mere infections by a bacterial pathogen, but the consequence of mammary dysbiosis. This article develops the logical implications of this paradigm shift and shows how this concept is incompatible with current knowledge concerning the innate and adaptive immune system of the mammary gland of dairy ruminants. It also highlights how the concept of mammary microbiota clashes with results of experimental infections induced under controlled conditions or large field experiments that demonstrated the efficacy of the current mastitis control measures.

STAT signaling in mammary gland differentiation, cell survival and tumorigenesis.

PubMed

Haricharan, S; Li, Y

2014-01-25

The mammary gland is a unique organ that undergoes extensive and profound changes during puberty, menstruation, pregnancy, lactation and involution. The changes that take place during puberty involve large-scale proliferation and invasion of the fat-pad. During pregnancy and lactation, the mammary cells are exposed to signaling pathways that inhibit apoptosis, induce proliferation and invoke terminal differentiation. Finally, during involution the mammary gland is exposed to milk stasis, programmed cell death and stromal reorganization to clear the differentiated milk-producing cells. Not surprisingly, the signaling pathways responsible for bringing about these changes in breast cells are often subverted during the process of tumorigenesis. The STAT family of proteins is involved in every stage of mammary gland development, and is also frequently implicated in breast tumorigenesis. While the roles of STAT3 and STAT5 during mammary gland development and tumorigenesis are well studied, others members, e.g. STAT1 and STAT6, have only recently been observed to play a role in mammary gland biology. Continued investigation into the STAT protein network in the mammary gland will likely yield new biomarkers and risk factors for breast cancer, and may also lead to novel prophylactic or therapeutic strategies against breast cancer. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

STAT signaling in mammary gland differentiation, cell survival and tumorigenesis

PubMed Central

Haricharan, S; Li, Y

2013-01-01

The mammary gland is a unique organ that undergoes extensive and profound changes during puberty, menstruation, pregnancy, lactation and involution. The changes that take place during puberty involve large-scale proliferation and invasion of the fat-pad. During pregnancy and lactation, the mammary cells are exposed to signaling pathways that inhibit apoptosis, induce proliferation and invoke terminal differentiation. Finally, during involution the mammary gland is exposed to milk stasis, programed cell death and stromal reorganization to clear the differentiated milk-producing cells. Not surprisingly, the signaling pathways responsible for bringing about these changes in breast cells are often subverted during the process of tumorigenesis. The STAT family of proteins is involved in every stage of mammary gland development, and is also frequently implicated in breast tumorigenesis. While the roles of STAT3 and STAT5 during mammary gland development and tumorigenesis are well studied, others members, e.g. STAT1 and STAT6, have only recently been observed to play a role in mammary gland biology. Continued investigation into the STAT protein network in the mammary gland will likely yield new biomarkers and risk factors for breast cancer, and may also lead to novel prophylactic or therapeutic strategies against breast cancer. PMID:23541951

Quality of life, postnatal depression and baby gender.

PubMed

de Tychey, Claude; Briançon, Serge; Lighezzolo, Joëlle; Spitz, Elisabeth; Kabuth, Bernard; de Luigi, Valerie; Messembourg, Catherine; Girvan, Françoise; Rosati, Aurore; Thockler, Audrey; Vincent, Stephanie

2008-02-01

To study the impact of postnatal depression on the quality of life of young French mothers and to evaluate if the gender of their child influences this. Postnatal depression (PND) constitutes a major public health problem considering its high prevalence and consequences upon quality of life and parental skills. This research is a cross-sectional study during the postnatal period. This study was carried out during a two-month period. Data were collected by interview and questionnaires. The authors compared the prevalence rate of PND and life quality in a cohort of 181 women and measured the short-term impact of the child's birth. Postnatal depression strongly negatively influences all dimensions of life quality explored through the SF36, e.g. physical functioning (PF), physical Role (RP), bodily pain (BP), mental health (MH), emotional role (RE), social functioning (SF), vitality (VT), general health (GH), standardized physical component (PCS) and standardized mental component (MCS). The baby's gender (having a boy) also significantly reduces quality of life, irrespective of depressive state. There is a relationship between baby gender and PND. This research is the first to show that the birth of a boy reduces several dimensions of the mothers' quality of life. The importance of the impairment of quality of life in case of PND, as well as its effects on mother-child interaction, could justify prevention programs and early psychotherapeutic care. Further research needs to explore the effectiveness of programmes targeting the construction of parenting skills as a preventative measure against PND, especially for parents of boys.

Postnatal development of echolocation abilities in a bottlenose dolphin (Tursiops truncatus): temporal organization.

PubMed

Favaro, Livio; Gnone, Guido; Pessani, Daniela

2013-03-01

In spite of all the information available on adult bottlenose dolphin (Tursiops truncatus) biosonar, the ontogeny of its echolocation abilities has been investigated very little. Earlier studies have reported that neonatal dolphins can produce both whistles and burst-pulsed sounds just after birth and that early-pulsed sounds are probably a precursor of echolocation click trains. The aim of this research is to investigate the development of echolocation signals in a captive calf, born in the facilities of the Acquario di Genova. A set of 81 impulsive sounds were collected from birth to the seventh postnatal week and six additional echolocation click trains were recorded when the dolphin was 1 year old. Moreover, behavioral observations, concurring with sound production, were carried out by means of a video camera. For each sound we measured five acoustic parameters: click train duration (CTD), number of clicks per train, minimum, maximum, and mean click repetition rate (CRR). CTD and number of clicks per train were found to increase with age. Maximum and mean CRR followed a decreasing trend with dolphin growth starting from the second postnatal week. The calf's first head scanning movement was recorded 21 days after birth. Our data suggest that in the bottlenose dolphin the early postnatal weeks are essential for the development of echolocation abilities and that the temporal features of the echolocation click trains remain relatively stable from the seventh postnatal week up to the first year of life. © 2013 Wiley Periodicals, Inc.

Hormone-induced protection against mammary tumorigenesis is conserved in multiple rat strains and identifies a core gene expression signature induced by pregnancy.

PubMed

Blakely, Collin M; Stoddard, Alexander J; Belka, George K; Dugan, Katherine D; Notarfrancesco, Kathleen L; Moody, Susan E; D'Cruz, Celina M; Chodosh, Lewis A

2006-06-15

Women who have their first child early in life have a substantially lower lifetime risk of breast cancer. The mechanism for this is unknown. Similar to humans, rats exhibit parity-induced protection against mammary tumorigenesis. To explore the basis for this phenomenon, we identified persistent pregnancy-induced changes in mammary gene expression that are tightly associated with protection against tumorigenesis in multiple inbred rat strains. Four inbred rat strains that exhibit marked differences in their intrinsic susceptibilities to carcinogen-induced mammary tumorigenesis were each shown to display significant protection against methylnitrosourea-induced mammary tumorigenesis following treatment with pregnancy levels of estradiol and progesterone. Microarray expression profiling of parous and nulliparous mammary tissue from these four strains yielded a common 70-gene signature. Examination of the genes constituting this signature implicated alterations in transforming growth factor-beta signaling, the extracellular matrix, amphiregulin expression, and the growth hormone/insulin-like growth factor I axis in pregnancy-induced alterations in breast cancer risk. Notably, related molecular changes have been associated with decreased mammographic density, which itself is strongly associated with decreased breast cancer risk. Our findings show that hormone-induced protection against mammary tumorigenesis is widely conserved among divergent rat strains and define a gene expression signature that is tightly correlated with reduced mammary tumor susceptibility as a consequence of a normal developmental event. Given the conservation of this signature, these pathways may contribute to pregnancy-induced protection against breast cancer.

Leptin expression in human mammary epithelial cells and breast milk.

PubMed

Smith-Kirwin, S M; O'Connor, D M; De Johnston, J; Lancey, E D; Hassink, S G; Funanage, V L

1998-05-01

Leptin has recently been shown to be produced by the human placenta and potentially plays a role in fetal and neonatal growth. Many functions of the placenta are replaced by the mammary gland in terms of providing critical growth factors for the newborn. In this study, we show that leptin is produced by human mammary epithelial cells as revealed by RT/PCR analysis of total RNA from mammary gland and immunohistochemical staining of breast tissue, cultured mammary epithelial cells, and secretory epithelial cells present in human milk. We also verify that immunoreactive leptin is present in whole milk at 30- to 150-fold higher concentrations than skim milk. We propose that leptin is secreted by mammary epithelial cells in milk fat globules, which partition into the lipid portion of breast milk.

Antenatal interpersonal sensitivity is more strongly associated than perinatal depressive symptoms with postnatal mother-infant interaction quality.

PubMed

Raine, Karen; Cockshaw, Wendell; Boyce, Philip; Thorpe, Karen

2016-10-01

Maternal mental health has enduring effects on children's life chances and is a substantial cost driver for child health, education and social services. A key linking mechanism is the quality of mother-infant interaction. A body of work associates maternal depressive symptoms across the antenatal and postnatal (perinatal) period with less-than-optimal mother-infant interaction. Our study aims to build on previous research in the field through exploring the association of a maternal personality trait, interpersonal sensitivity, measured in early pregnancy, with subsequent mother-infant interaction quality. We analysed data from the Avon Longitudinal Study of Parents and Children (ALSPAC) to examine the association between antenatal interpersonal sensitivity and postnatal mother-infant interaction quality in the context of perinatal depressive symptoms. Interpersonal sensitivity was measured during early pregnancy and depressive symptoms in the antenatal year and across the first 21 months of the postnatal period. In a subsample of the ALSPAC, mother-infant interaction was measured at 12 months postnatal through a standard observation. For the subsample that had complete data at all time points (n = 706), hierarchical regression examined the contribution of interpersonal sensitivity to variance in mother-infant interaction quality. Perinatal depressive symptoms predicted little variance in mother-infant interaction. Antenatal interpersonal sensitivity explained a greater proportion of variance in mother-infant interaction quality. The personality trait, interpersonal sensitivity, measured in early pregnancy, is a more robust indicator of subsequent mother-infant-interaction quality than perinatal depressive symptoms, thus affording enhanced opportunity to identify vulnerable mother-infant relationships for targeted early intervention.

Postnatal cocaine exposure: effects on behavior of rats in forced swim test.

PubMed

Magalhães, Ana; Tavares, Maria Amélia; de Sousa, Liliana

2002-06-01

Exposure to cocaine in early periods of postnatal life has adverse effects on behavior, namely, it induces the display of anxiety and fear-like behaviors that are associated with stress and depression. This study examined the effects of early developmental cocaine exposure in several categories of behavior observed in forced swim test. Male and female Wistar rats were given 15 mg/kg of cocaine hydrochloride/body weight/day, subcutaneously, in two daily doses, from postnatal day (PND) 1 to PND27. Controls were saline injected in the same protocol. In PND26-PND27, rats were placed in a swimming pool during 5 min in two sessions. The categories of behavior studied in this work included horizontal and vertical rotation, vibrissae clean, head clean, fast and slow swim, struggling, floating, sliding, diving, head-diving, and wagging head. Results showed differences in the frequencies of several behavioral categories that allowed the discrimination of the behaviors that may constitute "behavioral despair" indicators, as well as which behaviors are most affected by cocaine exposure. Cocaine groups were less active and more immobile than controls. These results suggest that postnatal exposure to cocaine can produce depression-like effects and affect the ability of these animals to cope with stress situations.

The Type 7 Serotonin Receptor, 5-HT7, Is Essential in the Mammary Gland for Regulation of Mammary Epithelial Structure and Function

PubMed Central

Pai, Vaibhav P.; Hernandez, Laura L.; Stull, Malinda A.; Horseman, Nelson D.

2015-01-01

Autocrine-paracrine activity of serotonin (5-hydroxytryptamine, 5-HT) is a crucial homeostatic parameter in mammary gland development during lactation and involution. Published studies suggested that the 5-HT7 receptor type was important for mediating several effects of 5-HT in the mammary epithelium. Here, using 5-HT7 receptor-null (HT7KO) mice we attempt to understand the role of this receptor in mediating 5-HT actions within the mammary gland. We demonstrate for the first time that HT7KO dams are inefficient at sustaining their pups. Histologically, the HT7KO mammary epithelium shows a significant deviation from the normal secretory epithelium in morphological architecture, reduced secretory vesicles, and numerous multinucleated epithelial cells with atypically displaced nuclei, during lactation. Mammary epithelial cells in HT7KO dams also display an inability to transition from lactation to involution as normally seen by transition from a columnar to a squamous cell configuration, along with alveolar cell apoptosis and cell shedding. Our results show that 5-HT7 is required for multiple actions of 5-HT in the mammary glands including core functions that contribute to changes in cell shape and cell turnover, as well as specialized secretory functions. Understanding these actions may provide new interventions to improve lactation performance and treat diseases such as mastitis and breast cancer. PMID:25664318

Stress during a Critical Postnatal Period Induces Region-Specific Structural Abnormalities and Dysfunction of the Prefrontal Cortex via CRF1

PubMed Central

Yang, Xiao-Dun; Liao, Xue-Mei; Uribe-Mariño, Andrés; Liu, Rui; Xie, Xiao-Meng; Jia, Jiao; Su, Yun-Ai; Li, Ji-Tao; Schmidt, Mathias V; Wang, Xiao-Dong; Si, Tian-Mei

2015-01-01

During the early postnatal period, environmental influences play a pivotal role in shaping the development of the neocortex, including the prefrontal cortex (PFC) that is crucial for working memory and goal-directed actions. Exposure to stressful experiences during this critical period may disrupt the development of PFC pyramidal neurons and impair the wiring and function of related neural circuits. However, the molecular mechanisms of the impact of early-life stress on PFC development and function are not well understood. In this study, we found that repeated stress exposure during the first postnatal week hampered dendritic development in layers II/III and V pyramidal neurons in the dorsal agranular cingulate cortex (ACd) and prelimbic cortex (PL) of neonatal mice. The deleterious effects of early postnatal stress on structural plasticity persisted to adulthood only in ACd layer V pyramidal neurons. Most importantly, concurrent blockade of corticotropin-releasing factor receptor 1 (CRF1) by systemic antalarmin administration (20 μg/g of body weight) during early-life stress exposure prevented stress-induced apical dendritic retraction and spine loss in ACd layer V neurons and impairments in PFC-dependent cognitive tasks. Moreover, the magnitude of dendritic regression, especially the shrinkage of apical branches, of ACd layer V neurons predicted the degree of cognitive deficits in stressed mice. Our data highlight the region-specific effects of early postnatal stress on the structural plasticity of prefrontal pyramidal neurons, and suggest a critical role of CRF1 in modulating early-life stress-induced prefrontal abnormalities. PMID:25403725

Postnatal effects of intrauterine treatment of the growth-restricted ovine fetus with intra-amniotic insulin-like growth factor-1.

PubMed

Spiroski, A M; Oliver, M H; Jaquiery, A L; Prickett, T C R; Espiner, E A; Harding, J E; Bloomfield, F H

2017-12-12

Fetal growth restriction increases the risk of fetal and neonatal mortality and morbidity, and contributes to increased risk of chronic disease later in life. Intra-amniotic insulin-like growth factor-1 (IGF1) treatment of the growth-restricted ovine fetus improves fetal growth, but postnatal effects are unknown. Here we report that intra-amniotic IGF1 treatment of the growth-restricted ovine fetus alters size at birth and mechanisms of early postnatal growth in a sex-specific manner. We also show that maternal plasma C-type natriuretic peptide (CNP) products are related to fetal oxygenation and size at birth, and hence may be useful for non-invasive monitoring of fetal growth restriction. Intrauterine IGF1 treatment in late gestation is a potentially clinically relevant intervention that may ameliorate the postnatal complications of fetal growth restriction. Placental insufficiency-mediated fetal growth restriction (FGR) is associated with altered postnatal growth and metabolism, which are, in turn, associated with increased risk of adult disease. Intra-amniotic insulin-like growth factor-1 (IGF1) treatment of ovine FGR increases growth rate in late gestation, but the effects on postnatal growth and metabolism are unknown. We investigated the effects of intra-amniotic IGF1 administration to ovine fetuses with uteroplacental embolisation-induced FGR on phenotypical and physiological characteristics in the 2  weeks after birth. We measured early postnatal growth velocity, amino-terminal propeptide of C-type natriuretic peptide (NTproCNP), body composition, tissue-specific mRNA expression, and milk intake in singleton lambs treated weekly with 360 μg intra-amniotic IGF1 (FGRI; n = 13 females, 19 males) or saline (FGRS; n = 18 females, 12 males) during gestation, and in controls (CON; n = 15 females, 22 males). There was a strong positive correlation between maternal NTproCNP and fetal oxygenation, and size at birth in FGR lambs. FGR lambs were ∼20% lighter

Single-cell RNA-Seq reveals cell heterogeneity and hierarchy within mouse mammary epithelia.

PubMed

Sun, Heng; Miao, Zhengqiang; Zhang, Xin; Chan, Un In; Su, Sek Man; Guo, Sen; Wong, Chris Koon Ho; Xu, Xiaoling; Deng, Chu-Xia

2018-06-01

The mammary gland is very intricately and well organized into distinct tissues, including epithelia, endothelia, adipocytes, and stromal and immune cells. Many mammary gland diseases, such as breast cancer, arise from abnormalities in the mammary epithelium, which is mainly composed of two distinct lineages, the basal and luminal cells. Because of the limitation of traditional transcriptome analysis of bulk mammary cells, the hierarchy and heterogeneity of mammary cells within these two lineages remain unclear. To this end, using single-cell RNA-Seq coupled with FACS analysis and principal component analysis, we determined gene expression profiles of mammary epithelial cells of virgin and pregnant mice. These analyses revealed a much higher heterogeneity among the mammary cells than has been previously reported and enabled cell classification into distinct subgroups according to signature gene markers present in each group. We also identified and verified a rare CDH5 + cell subpopulation within a basal cell lineage as quiescent mammary stem cells (MaSCs). Moreover, using pseudo-temporal analysis, we reconstructed the developmental trajectory of mammary epithelia and uncovered distinct changes in gene expression and in biological functions of mammary cells along the developmental process. In conclusion, our work greatly refines the resolution of the cellular hierarchy in developing mammary tissues. The discovery of CDH5 + cells as MaSCs in these tissues may have implications for our understanding of the initiation, development, and pathogenesis of mammary tumors. © 2018 Sun et al.

Beneficial effects of postnatal choline supplementation on long-Term neurocognitive deficit resulting from fetal-Neonatal iron deficiency.

PubMed

Kennedy, Bruce C; Tran, Phu V; Kohli, Maulika; Maertens, Jamie J; Gewirtz, Jonathan C; Georgieff, Michael K

2018-01-15

Early-life iron deficiency is a common nutrient condition worldwide and can result in cognitive impairment in adulthood despite iron treatment. In rodents, prenatal choline supplementation can diminish long-term hippocampal gene dysregulation and neurocognitive deficits caused by iron deficiency. Since fetal iron status is generally unknown in humans, we determined whether postnatal choline supplementation exerts similar beneficial effects. Male rat pups were made iron deficient (ID) by providing pregnant and nursing dams an ID diet (3-6ppm Fe) from gestational day (G) 3 through postnatal day (P) 7, and an iron-sufficient (IS) diet (200ppm Fe) thereafter. Control pups were provided IS diet throughout. Choline (5ppm) was given to half the nursing dams and weanlings in each group from P11-P30. P65 rat cognitive performance was assessed by novel object recognition (NOR). Real-time PCR was performed to validate expression levels of synaptic plasticity genes known to be dysregulated by early-life iron deficiency. Postnatal choline supplementation prevented impairment of NOR memory in formerly iron-deficient (FID) adult rats but impaired NOR memory in IS controls. Gene expression analysis revealed a recovery of 4 out of 10 dysregulated genes compared to 8 of the same 10 genes that we previously demonstrated to recover following prenatal choline supplementation. Recognition memory deficits induced by early-life iron deficiency can be prevented by postnatal choline supplementation and disrupted expression of a subset of synaptic plasticity genes can be ameliorated. The positive response to postnatal choline represents a potential adjunctive therapeutic supplement to treat iron-deficient anemic children in order to spare long-term neurodevelopmental deficits. Copyright © 2017. Published by Elsevier B.V.

Growth hormone mRNA in mammary gland tumors of dogs and cats.

PubMed Central

Mol, J A; van Garderen, E; Selman, P J; Wolfswinkel, J; Rijinberk, A; Rutteman, G R

1995-01-01

We have shown recently that in the dog progestin administration results in mammary production of immunoreactive growth hormone (GH). At present we demonstrate the expression of the gene encoding GH in the mammary gland of dogs and cats using reverse-transcriptase PCR. GH mRNA was found in the great majority of normal mammary tissues as well as benign and malignant mammary tumors of the dog and was associated with the presence of immunoreactive GH in cryostat sections. The mammary PCR product proved to be identical to that of the pituitary. The highest expression levels were found after prolonged treatment with progestins. In carcinomas GH mRNA was also found in progesterone receptor-negative tissue samples, indicating that after malignant transformation GH gene expression may become progestin independent. GH mRNA was also present in mammary tissues of cats with progestin-induced fibroadenomatous changes. It is concluded that GH gene expression occurs in normal, hyperplastic, and neoplastic mammary tissue of the dog. The expression in normal tissue is stimulated by progestins and might mediate the progestin-stimulated development of canine mammary tumors. The demonstration of progestin-stimulated GH expression in mammary tissue of cats indicates that the phenomenon is more generalized among mammals. Images PMID:7738169

Mammary fibroadenomatous hyperplasia in a male cat.

PubMed

Mayayo, Saray Lorna; Bo, Stefano; Pisu, Maria Carmela

2018-01-01

Mammary fibroadenomatous hyperplasia (MFH) is a benign pathology characterised by extensive proliferation of the ductal epithelium and mammary stroma. It typically occurs in young female cats, and seems to result from hypersensitivity to progesterone. A 2-year-old entire male European Shorthair cat presented to the veterinary clinic with enlargement of several mammary glands, which had developed within the previous 10 days. There was no prior administration of progestin in the cat's medical history. Diagnostic tests were performed to assess the basal progesterone concentration and the concentration after stimulation with gonadotropin-releasing hormone, which ruled out the presence of functional ovarian tissue. Histological examination of the testes excluded hormone-secreting testicular tumours. Histological examination of the mammary gland confirmed the diagnosis of MFH. Treatment was started with aglepristone, a selective competitor for progesterone receptors, administered subcutaneously at 15 mg/kg at days 1, 2, 8 and 15. A reduction in the size of the mammary glands was evident 6 days after the first administration, with complete remission observed after 4 weeks. To the best of our knowledge, this is the first full report of MFH in a male cat. Although the origin of the progestins responsible for MFH in this case could not be confirmed, in the light of the diagnostic tests performed and the results obtained, accidental contact with hormone-like substances seems to be the only plausible explanation for the cat's clinical signs. Inhibitor therapy was successful.

Folic Acid Supplementation Promotes Mammary Tumor Progression in a Rat Model

PubMed Central

Deghan Manshadi, Shaidah; Ishiguro, Lisa; Sohn, Kyoung-Jin; Medline, Alan; Renlund, Richard; Croxford, Ruth; Kim, Young-In

2014-01-01

Folic acid supplementation may prevent the development of cancer in normal tissues but may promote the progression of established (pre)neoplastic lesions. However, whether or not folic acid supplementation can promote the progression of established (pre)neoplastic mammary lesions is unknown. This is a critically important issue because breast cancer patients and survivors in North America are likely exposed to high levels of folic acid owing to folic acid fortification and widespread supplemental use after cancer diagnosis. We investigated whether folic acid supplementation can promote the progression of established mammary tumors. Female Sprague-Dawley rats were placed on a control diet and mammary tumors were initiated with 7,12-dimethylbenza[a]anthracene at puberty. When the sentinel tumor reached a predefined size, rats were randomized to receive a diet containing the control, 2.5x, 4x, or 5x supplemental levels of folic acid for up to 12 weeks. The sentinel mammary tumor growth was monitored weekly. At necropsy, the sentinel and all other mammary tumors were analyzed histologically. The effect of folic acid supplementation on the expression of proteins involved in proliferation, apoptosis, and mammary tumorigenesis was determined in representative sentinel adenocarcinomas. Although no clear dose-response relationship was observed, folic acid supplementation significantly promoted the progression of the sentinel mammary tumors and was associated with significantly higher sentinel mammary tumor weight and volume compared with the control diet. Furthermore, folic acid supplementation was associated with significantly higher weight and volume of all mammary tumors. The most significant and consistent mammary tumor-promoting effect was observed with the 2.5x supplemental level of folic acid. Folic acid supplementation was also associated with an increased expression of BAX, PARP, and HER2. Our data suggest that folic acid supplementation may promote the progression

The amyloid precursor protein and postnatal neurogenesis/neuroregeneration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen Yanan; Tang, Bor Luen

2006-03-03

The amyloid precursor protein (APP) is the source of amyloid-beta (A{beta}) peptide, produced via its sequential cleavage {beta}- and {gamma}-secretases. Various biophysical forms of A{beta} (and the mutations of APP which results in their elevated levels) have been implicated in the etiology and early onset of Alzheimer's disease. APP's evolutionary conservation and the existence of APP-like isoforms (APLP1 and APLP2) which lack the A{beta} sequence, however, suggest that these might have important physiological functions that are unrelated to A{beta} production. Soluble N-terminal fragments of APP have been known to be neuroprotective, and the interaction of its cytoplasmic C-terminus with amore » myriad of proteins associates it with diverse processes such as axonal transport and transcriptional regulation. The notion for an essential postnatal function of APP has been demonstrated genetically, as mice deficient in both APP and APLP2 or all three APP isoforms exhibit early postnatal lethality and neuroanatomical abnormalities. Recent findings have also brought to light two possible functions of the APP family in Brain-regulation of neural progenitor cell proliferation and axonal outgrowth after injury. Interestingly, these two apparently related neurogenic/neuroregenerative functions of APP involve two separate domains of the molecule.« less

The Effects of Maternal Postnatal Depression and Child Sex on Academic Performance at Age 16 Years: A Developmental Approach

ERIC Educational Resources Information Center

Murray, Lynne; Arteche, Adriane; Fearon, Pasco; Halligan, Sarah; Croudace, Tim; Cooper, Peter

2010-01-01

Background: Postnatal depression (PND) is associated with poor cognitive functioning in infancy and the early school years; long-term effects on academic outcome are not known. Method: Children of postnatally depressed (N = 50) and non-depressed mothers (N = 39), studied from infancy, were followed up at 16 years. We examined the effects on…

Understanding exercise self-efficacy and barriers to leisure-time physical activity among postnatal women.

PubMed

Cramp, Anita G; Bray, Steven R

2011-07-01

Studies have demonstrated that postnatal women are at high risk for physical inactivity and generally show lower levels of leisure-time physical activity (LTPA) compared to prepregnancy. The overall purpose of the current study was to investigate social cognitive correlates of LTPA among postnatal women during a 6-month period following childbirth. A total of 230 women (mean age = 30.9) provided descriptive data regarding barriers to LTPA and completed measures of LTPA and self-efficacy (exercise and barrier) for at least one of the study data collection periods. A total of 1,520 barriers were content analyzed. Both exercise and barrier self-efficacy were positively associated with subsequent LTPA. Exercise self-efficacy at postnatal week 12 predicted LTPA from postnatal weeks 12 to 18 (β = .40, R (2) = .18) and exercise self-efficacy at postnatal week 24 predicted LTPA during weeks 24-30 (β = .49, R (2) = .30). Barrier self-efficacy at week 18 predicted LTPA from weeks 18 to 24 (β = .33, R (2) = .13). The results of the study identify a number of barriers to LTPA at multiple time points closely following childbirth which may hinder initiation, resumption or maintenance of LTPA. The results also suggest that higher levels of exercise and barrier self-efficacy are prospectively associated with higher levels of LTPA in the early postnatal period. Future interventions should be designed to investigate causal effects of developing participants' exercise and barrier self-efficacy for promoting and maintaining LTPA during the postnatal period.

Lifetime genistein intake increases the response of mammary tumors to tamoxifen in rats

PubMed Central

Zhang, Xiyuan; Cook, Katherine L; Warri, Anni; Cruz, Idalia M; Rosim, Mariana; Riskin, Jeffrey; Helferich, William; Doerge, Daniel; Clarke, Robert; Hilakivi-Clarke, Leena

2016-01-01

Purpose Whether it is safe for estrogen receptor positive (ER+) breast cancer patients to consume soy isoflavone genistein (GEN) remains controversial. We compared the effects of GEN intake mimicking either Asian (lifetime) or Caucasian (adulthood) intake patterns to that of starting its intake during tamoxifen (TAM) therapy using a preclinical model. Experimental Design Female Sprague-Dawley rats were fed an AIN93G diet supplemented with 0 (control diet) or 500 ppm GEN from postnatal day 15 onwards (lifetime GEN). Mammary tumors were induced with 7,12-dimethylbenz(a)anthracene (DMBA), after which a group of control diet fed rats were switched to GEN diet (adult GEN). When the first tumor in a rat reached 1.4 cm in diameter, TAM was added to the diet, and a subset of previously only control diet fed rats also started GEN intake (post-diagnosis GEN). Results Lifetime GEN intake reduced de novo resistance to TAM, compared with post-diagnosis GEN groups. Risk of recurrence was lower both in the lifetime and adult GEN groups than in the post-diagnosis GEN group. We observed downregulation of unfolded protein response (UPR) and autophagy related genes (GRP78, IRE1α, ATF4 and Beclin-1), and genes linked to immunosuppression (TGFβ and Foxp3), and upregulation of cytotoxic T cell marker CD8a in the tumors of the lifetime GEN group, compared with controls, post-diagnosis, and/or adult GEN groups. Conclusions GEN intake mimicking Asian consumption patterns improved response of mammary tumors to TAM therapy, and this effect was linked to reduced activity of UPR and pro-survival autophagy signaling, and increased anti-tumor immunity. PMID:28148690

Development of novel murine mammary imaging windows to examine wound healing effects on leukocyte trafficking in mammary tumors with intravital imaging

PubMed Central

Sobolik, Tammy; Su, Ying-Jun; Ashby, Will; Schaffer, David K.; Wells, Sam; Wikswo, John P.; Zijlstra, Andries; Richmond, Ann

2016-01-01

ABSTRACT We developed mammary imaging windows (MIWs) to evaluate leukocyte infiltration and cancer cell dissemination in mouse mammary tumors imaged by confocal microscopy. Previous techniques relied on surgical resection of a skin flap to image the tumor microenvironment restricting imaging time to a few hours. Utilization of mammary imaging windows offers extension of intravital imaging of the tumor microenvironment. We have characterized strengths and identified some previously undescribed potential weaknesses of MIW techniques. Through iterative enhancements of a transdermal portal we defined conditions for improved quality and extended confocal imaging time for imaging key cell-cell interactions in the tumor microenvironment. PMID:28243517

Development of novel murine mammary imaging windows to examine wound healing effects on leukocyte trafficking in mammary tumors with intravital imaging.

PubMed

Sobolik, Tammy; Su, Ying-Jun; Ashby, Will; Schaffer, David K; Wells, Sam; Wikswo, John P; Zijlstra, Andries; Richmond, Ann

2016-01-01

We developed mammary imaging windows (MIWs) to evaluate leukocyte infiltration and cancer cell dissemination in mouse mammary tumors imaged by confocal microscopy. Previous techniques relied on surgical resection of a skin flap to image the tumor microenvironment restricting imaging time to a few hours. Utilization of mammary imaging windows offers extension of intravital imaging of the tumor microenvironment. We have characterized strengths and identified some previously undescribed potential weaknesses of MIW techniques. Through iterative enhancements of a transdermal portal we defined conditions for improved quality and extended confocal imaging time for imaging key cell-cell interactions in the tumor microenvironment.

Growth trajectories in early childhood, their relationship with antenatal and postnatal factors, and development of obesity by age 9 years: results from an Australian birth cohort study.

PubMed

Giles, L C; Whitrow, M J; Davies, M J; Davies, C E; Rumbold, A R; Moore, V M

2015-07-01

In an era where around one in four children in the United Kingdom, the United States, and Australia are overweight or obese, the development of obesity in early life needs to be better understood. We aimed to identify groups of children with distinct trajectories of growth in infancy and early childhood, to examine any association between these trajectories and body size at age 9, and to assess the relative influence of antenatal and postnatal exposures on growth trajectories. Prospective Australian birth cohort study. In total, 557 children with serial height and weight measurements from birth to 9 years were included in the study. Latent class growth models were used to derive distinct groups of growth trajectories from birth to age 3½ years. Multivariable logistic regression models were used to explore antenatal and postnatal predictors of growth trajectory groups, and multivariable linear and logistic regression models were used to examine the relationships between growth trajectory groups and body size at age 9 years. We identified four discrete growth trajectories from birth to age 3½ years, characterised as low, intermediate, high, or accelerating growth. Relative to the intermediate growth group, the low group had reduced z-body mass index (BMI) (-0.75 s.d.; 95% confidence interval (CI) -1.02, -0.47), and the high and accelerating groups were associated with increased body size at age 9 years (high: z-BMI 0.70 s.d.; 95% CI 0.49, 0.62; accelerating: z-BMI 1.64 s.d.; 95% CI 1.16, 2.11). Of the antenatal and postnatal exposures considered, the most important differentiating factor was maternal obesity in early pregnancy, associated with a near quadrupling of risk of membership of the accelerating growth trajectory group compared with the intermediate growth group (odds ratio (OR) 3.72; 95% CI 1.15, 12.05). Efforts to prevent childhood obesity may need to be embedded within population-wide strategies that also pay attention to healthy weight for women in

Genomic and Phenomic Study of Mammary Pathogenic Escherichia coli

PubMed Central

Blum, Shlomo E.; Heller, Elimelech D.; Sela, Shlomo; Elad, Daniel; Edery, Nir; Leitner, Gabriel

2015-01-01

Escherichia coli is a major etiological agent of intra-mammary infections (IMI) in cows, leading to acute mastitis and causing great economic losses in dairy production worldwide. Particular strains cause persistent IMI, leading to recurrent mastitis. Virulence factors of mammary pathogenic E. coli (MPEC) involved pathogenesis of mastitis as well as those differentiating strains causing acute or persistent mastitis are largely unknown. This study aimed to identify virulence markers in MPEC through whole genome and phenome comparative analysis. MPEC strains causing acute (VL2874 and P4) or persistent (VL2732) mastitis were compared to an environmental strain (K71) and to the genomes of strains representing different E. coli pathotypes. Intra-mammary challenge in mice confirmed experimentally that the strains studied here have different pathogenic potential, and that the environmental strain K71 is non-pathogenic in the mammary gland. Analysis of whole genome sequences and predicted proteomes revealed high similarity among MPEC, whereas MPEC significantly differed from the non-mammary pathogenic strain K71, and from E. coli genomes from other pathotypes. Functional features identified in MPEC genomes and lacking in the non-mammary pathogenic strain were associated with synthesis of lipopolysaccharide and other membrane antigens, ferric-dicitrate iron acquisition and sugars metabolism. Features associated with cytotoxicity or intra-cellular survival were found specifically in the genomes of strains from severe and acute (VL2874) or persistent (VL2732) mastitis, respectively. MPEC genomes were relatively similar to strain K-12, which was subsequently shown here to be possibly pathogenic in the mammary gland. Phenome analysis showed that the persistent MPEC was the most versatile in terms of nutrients metabolized and acute MPEC the least. Among phenotypes unique to MPEC compared to the non-mammary pathogenic strain were uric acid and D-serine metabolism. This study

Pre- and postnatal stress and asthma in children: Temporal- and sex-specific associations

PubMed Central

Lee, Alison; Chiu, Yueh-Hsiu Mathilda; Rosa, Maria José; Jara, Calvin; Wright, Robert O.; Coull, Brent A.; Wright, Rosalind J.

2016-01-01

BACKGROUND Temporal- and sex-specific effects of perinatal stress have not been examined for childhood asthma. OBJECTIVES We examined associations between pre- and/or postnatal stress and children's asthma (n=765) and effect modification by sex in a prospective cohort study. METHODS Maternal negative life events (NLEs) were ascertained prenatally and postpartum. NLEs scores were categorized as 0, 1-2, 3-4, or ≥5 to assess exposure-response relationships. We examined effects of pre- and postnatal stress on children's asthma by age 6 years modeling each as independent predictors; mutually adjusting for prenatal and postnatal stress; and finally considering interactions between pre- and postnatal stress. Effect modification by sex was examined in stratified analyses and by fitting interaction terms. RESULTS When considering stress in each period independently, among boys a dose-response relationship was evident for each level increase on the ordinal scale prenatally (OR=1.38, 95% CI 1.06, 1.79; p-for-trend=0.03) and postnatally (OR=1.53, 95% CI 1.16, 2.01; p-for-trend=0.001); among girls only the postnatal trend was significant (OR=1.60, 95% CI 1.14, 2.22; p-for-trend=0.005). Higher stress in both the pre- and postnatal periods was associated with increased odds of being diagnosed with asthma in girls [OR=1.37, 95% CI 0.98, 1.91 (pinteraction=0.07)] but not boys [OR=1.08, 95% CI 0.82, 1.42 (pinteraction=0.61)]. CONCLUSIONS While boys were more vulnerable to stress during the prenatal period, girls were more impacted by postnatal stress and cumulative stress across both periods in relation to asthma. Understanding sex and temporal differences in response to early life stress may provide unique insight into asthma etiology and natural history. PMID:26953156

Antenatal/early postnatal hypothyroidism alters arterial tone regulation in 2-week-old rats.

PubMed

Sofronova, Svetlana I; Gaynullina, Dina K; Shvetsova, Anastasia A; Borzykh, Anna A; Selivanova, Ekaterina K; Kostyunina, Daria S; Sharova, Anna P; Martyanov, Andrey A; Tarasova, Olga S

2017-11-01

The mechanisms of vascular alterations resulting from early thyroid hormones deficiency are poorly understood. We tested the hypothesis that antenatal/early postnatal hypothyroidism would alter the activity of endothelial NO pathway and Rho-kinase pathway, which are specific for developing vasculature. Dams were treated with propylthiouracil (PTU, 7 ppm) in drinking water during gestation and 2 weeks after delivery, and their progeny had normal body weight but markedly reduced blood levels of thyroid hormones (ELISA). Small arteries from 2-week-old male pups were studied using wire myography, qPCR and Western blotting. Mesenteric arteries of PTU pups, compared to controls, demonstrated smaller maximum response to α 1 -adrenergic agonist methoxamine and reduced mRNA contents of smooth muscle differentiation markers α-actin and SERCA2A. Inhibition of basal NO synthesis by l-NNA led to tonic contraction of mesenteric arteries and augmented their contractile responses to methoxamine; both l-NNA effects were impaired in PTU pups. PTU pups demonstrated lower blood level of NO metabolites compared to control group (Griess reaction). Rho-kinase inhibitor Y27632 strongly reduced mesenteric arteries responses to methoxamine in PTU pups, that was accompanied by elevated Rho-kinase content in their arteries in comparison to control ones. Unlike mesenteric, saphenous arteries of PTU pups, compared to controls, had no changes in α-actin and SERCA2A contents and in responses to l-NNA and Y27632. In conclusion, thyroid hormones deficiency suppresses the anticontractile effect of NO and potentiates the procontractile Rho-kinase effects in mesenteric arteries of 2-week-old pups. Such alterations disturb perinatal cardiovascular homeostasis and might lead to cardiovascular pathologies in adulthood. © 2017 Society for Endocrinology.

Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis.

PubMed

Visvader, Jane E

2009-11-15

The epithelium of the mammary gland exists in a highly dynamic state, undergoing dramatic morphogenetic changes during puberty, pregnancy, lactation, and regression. The recent identification of stem and progenitor populations in mouse and human mammary tissue has provided evidence that the mammary epithelium is organized in a hierarchical manner. Characterization of these normal epithelial subtypes is an important step toward understanding which cells are predisposed to oncogenesis. This review summarizes progress in the field toward defining constituent cells and key molecular regulators of the mammary epithelial hierarchy. Potential relationships between normal epithelial populations and breast tumor subtypes are discussed, with implications for understanding the cellular etiology underpinning breast tumor heterogeneity.

Mammary fibroadenomatous hyperplasia in a male cat

PubMed Central

Mayayo, Saray Lorna; Bo, Stefano; Pisu, Maria Carmela

2018-01-01

Case summary Mammary fibroadenomatous hyperplasia (MFH) is a benign pathology characterised by extensive proliferation of the ductal epithelium and mammary stroma. It typically occurs in young female cats, and seems to result from hypersensitivity to progesterone. A 2-year-old entire male European Shorthair cat presented to the veterinary clinic with enlargement of several mammary glands, which had developed within the previous 10 days. There was no prior administration of progestin in the cat’s medical history. Diagnostic tests were performed to assess the basal progesterone concentration and the concentration after stimulation with gonadotropin-releasing hormone, which ruled out the presence of functional ovarian tissue. Histological examination of the testes excluded hormone-secreting testicular tumours. Histological examination of the mammary gland confirmed the diagnosis of MFH. Treatment was started with aglepristone, a selective competitor for progesterone receptors, administered subcutaneously at 15 mg/kg at days 1, 2, 8 and 15. A reduction in the size of the mammary glands was evident 6 days after the first administration, with complete remission observed after 4 weeks. Relevance and novel information To the best of our knowledge, this is the first full report of MFH in a male cat. Although the origin of the progestins responsible for MFH in this case could not be confirmed, in the light of the diagnostic tests performed and the results obtained, accidental contact with hormone-like substances seems to be the only plausible explanation for the cat’s clinical signs. Inhibitor therapy was successful. PMID:29568542

Stromal and Epithelial Caveolin-1 Both Confer a Protective Effect Against Mammary Hyperplasia and Tumorigenesis

PubMed Central

Williams, Terence M.; Sotgia, Federica; Lee, Hyangkyu; Hassan, Ghada; Di Vizio, Dolores; Bonuccelli, Gloria; Capozza, Franco; Mercier, Isabelle; Rui, Hallgeir; Pestell, Richard G.; Lisanti, Michael P.

2006-01-01

Here, we investigate the role of caveolin-1 (Cav-1) in breast cancer onset and progression, with a focus on epithelial-stromal interactions, ie, the tumor microenvironment. Cav-1 is highly expressed in adipocytes and is abundant in mammary fat pads (stroma), but it remains unknown whether loss of Cav-1 within mammary stromal cells affects the differentiated state of mammary epithelia via paracrine signaling. To address this issue, we characterized the development of the mammary ductal system in Cav-1−/− mice and performed a series of mammary transplant studies, using both wild-type and Cav-1−/− mammary fat pads. Cav-1−/− mammary epithelia were hyperproliferative in vivo, with dramatic increases in terminal end bud area and mammary ductal thickness as well as increases in bromodeoxyuridine incorporation, extracellular signal-regulated kinase-1/2 hyperactivation, and up-regulation of STAT5a and cyclin D1. Consistent with these findings, loss of Cav-1 dramatically exacerbated mammary lobulo-alveolar hyperplasia in cyclin D1 Tg mice, whereas overexpression of Cav-1 caused reversion of this phenotype. Most importantly, Cav-1−/− mammary stromal cells (fat pads) promoted the growth of both normal mammary ductal epithelia and mammary tumor cells. Thus, Cav-1 expression in both epithelial and stromal cells provides a protective effect against mammary hyperplasia as well as mammary tumorigenesis. PMID:17071600

The Origin and Significance of Mammary Intraductal Foam Cells

DTIC Science & Technology

2005-09-01

hematopoeitic origin developed in mammary tissue with both benign and malignant differentiation, depending on environmental cues. Progression of the cells...contribution of hematopoeitic precursors to the heterogeneity of cell types in benign and malignant mammary tissue.

Antenatal and early infant predictors of postnatal growth in rural Vietnam: a prospective cohort study

PubMed Central

Hanieh, Sarah; Ha, Tran T; De Livera, Alysha M; Simpson, Julie A; Thuy, Tran T; Khuong, Nguyen C; Thoang, Dang D; Tran, Thach D; Tuan, Tran; Fisher, Jane; Biggs, Beverley-Ann

2015-01-01

Objective To determine which antenatal and early-life factors were associated with infant postnatal growth in a resource-poor setting in Vietnam. Study design Prospective longitudinal study following infants (n=1046) born to women who had previously participated in a cluster randomised trial of micronutrient supplementation (ANZCTR:12610000944033), Ha Nam province, Vietnam. Antenatal and early infant factors were assessed for association with the primary outcome of infant length-for-age z scores at 6 months of age using multivariable linear regression and structural equation modelling. Results Mean length-for-age z score was −0.58 (SD 0.94) and stunting prevalence was 6.4%. Using structural equation modelling, we highlighted the role of infant birth weight as a predictor of infant growth in the first 6 months of life and demonstrated that maternal body mass index (estimated coefficient of 45.6 g/kg/m2; 95% CI 34.2 to 57.1), weight gain during pregnancy (21.4 g/kg; 95% CI 12.6 to 30.1) and maternal ferritin concentration at 32 weeks' gestation (−41.5 g per twofold increase in ferritin; 95% CI −78 to −5.0) were indirectly associated with infant length-for-age z scores at 6 months of age via birth weight. A direct association between 25-(OH) vitamin D concentration in late pregnancy and infant length-for-age z scores (estimated coefficient of −0.06 per 20 nmol/L; 95% CI −0.11 to −0.01) was observed. Conclusions Maternal nutritional status is an important predictor of early infant growth. Elevated antenatal ferritin levels were associated with suboptimal infant growth in this setting, suggesting caution with iron supplementation in populations with low rates of iron deficiency. PMID:25246090

Ectodysplasin/NF-κB Promotes Mammary Cell Fate via Wnt/β-catenin Pathway

PubMed Central

Voutilainen, Maria; Lönnblad, Darielle; Shirokova, Vera; Elo, Teresa; Rysti, Elisa; Schmidt-Ullrich, Ruth; Schneider, Pascal; Mikkola, Marja L.

2015-01-01

Mammary gland development commences during embryogenesis with the establishment of a species typical number of mammary primordia on each flank of the embryo. It is thought that mammary cell fate can only be induced along the mammary line, a narrow region of the ventro-lateral skin running from the axilla to the groin. Ectodysplasin (Eda) is a tumor necrosis factor family ligand that regulates morphogenesis of several ectodermal appendages. We have previously shown that transgenic overexpression of Eda (K14-Eda mice) induces formation of supernumerary mammary placodes along the mammary line. Here, we investigate in more detail the role of Eda and its downstream mediator transcription factor NF-κB in mammary cell fate specification. We report that K14-Eda mice harbor accessory mammary glands also in the neck region indicating wider epidermal cell plasticity that previously appreciated. We show that even though NF-κB is not required for formation of endogenous mammary placodes, it is indispensable for the ability of Eda to induce supernumerary placodes. A genome-wide profiling of Eda-induced genes in mammary buds identified several Wnt pathway components as potential transcriptional targets of Eda. Using an ex vivo culture system, we show that suppression of canonical Wnt signalling leads to a dose-dependent inhibition of supernumerary placodes in K14-Eda tissue explants. PMID:26581094

Monitoring In-Vivo the Mammary Gland Microstructure during Morphogenesis from Lactation to Post-Weaning Using Diffusion Tensor MRI.

PubMed

Nissan, Noam; Furman-Haran, Edna; Shapiro-Feinberg, Myra; Grobgeld, Dov; Degani, Hadassa

2017-09-01

Lactation and the return to the pre-conception state during post-weaning are regulated by hormonal induced processes that modify the microstructure of the mammary gland, leading to changes in the features of the ductal / glandular tissue, the stroma and the fat tissue. These changes create a challenge in the radiological workup of breast disorder during lactation and early post-weaning. Here we present non-invasive MRI protocols designed to record in vivo high spatial resolution, T 2 -weighted images and diffusion tensor images of the entire mammary gland. Advanced imaging processing tools enabled tracking the changes in the anatomical and microstructural features of the mammary gland from the time of lactation to post-weaning. Specifically, by using diffusion tensor imaging (DTI) it was possible to quantitatively distinguish between the ductal / glandular tissue distention during lactation and the post-weaning involution. The application of the T 2 -weighted imaging and DTI is completely safe, non-invasive and uses intrinsic contrast based on differences in transverse relaxation rates and water diffusion rates in various directions, respectively. This study provides a basis for further in-vivo monitoring of changes during the mammary developmental stages, as well as identifying changes due to malignant transformation in patients with pregnancy associated breast cancer (PABC).

Lrp4 and Wise interplay controls the formation and patterning of mammary and other skin appendage placodes by modulating Wnt signaling.

PubMed

Ahn, Youngwook; Sims, Carrie; Logue, Jennifer M; Weatherbee, Scott D; Krumlauf, Robb

2013-02-01

The future site of skin appendage development is marked by a placode during embryogenesis. Although Wnt/β-catenin signaling is known to be essential for skin appendage development, it is unclear which cellular processes are controlled by the signaling and how the precise level of the signaling activity is achieved during placode formation. We have investigated roles for Lrp4 and its potential ligand Wise (Sostdc1) in mammary and other skin appendage placodes. Lrp4 mutant mice displayed a delay in placode initiation and changes in distribution and number of mammary precursor cells leading to abnormal morphology, number and position of mammary placodes. These Lrp4 mammary defects, as well as limb defects, were associated with elevated Wnt/β-catenin signaling and were rescued by reducing the dose of the Wnt co-receptor genes Lrp5 and Lrp6, or by inactivating the gene encoding β-catenin. Wise-null mice phenocopied a subset of the Lrp4 mammary defects and Wise overexpression reduced the number of mammary precursor cells. Genetic epistasis analyses suggest that Wise requires Lrp4 to exert its function and that, together, they have a role in limiting mammary fate, but Lrp4 has an early Wise-independent role in facilitating placode formation. Lrp4 and Wise mutants also share defects in vibrissa and hair follicle development, suggesting that the roles played by Lrp4 and Wise are common to skin appendages. Our study presents genetic evidence for interplay between Lrp4 and Wise in inhibiting Wnt/β-catenin signaling and provides an insight into how modulation of Wnt/β-catenin signaling controls cellular processes important for skin placode formation.

Multimethod Approach to the Early Postnatal Growth of the Mandible in Mice from a Zone of Robertsonian Polymorphism.

PubMed

Martínez-Vargas, Jessica; Muñoz-Muñoz, Francesc; López-Fuster, María José; Cubo, Jorge; Ventura, Jacint

2018-04-18

The western European house mouse (Mus musculus domesticus) shows high karyotypic diversity owing to Robertsonian translocations. Morphometric studies conducted with adult mice suggest that karyotype evolution due to these chromosomal reorganizations entails variation in the form and the patterns of morphological covariation of the mandible. However, information is much scarcer regarding the effect of these rearrangements on the growth pattern of the mouse mandible over early postnatal ontogeny. Here we compare mandible growth from the second to the eighth week of postnatal life between two ontogenetic series of mice from wild populations, with the standard karyotype and with Robertsonian translocations respectively, reared under the same conditions. A multi-method approach is used, including bone histology analyses of mandible surfaces and cross-sections, as well as geometric morphometric analyses of mandible form. The mandibles of both standard and Robertsonian mice display growth acceleration around weaning, anteroposterior direction of bone maturation, a predominance of bone deposition fields over ontogeny, and relatively greater expansion of the posterior mandible region correlated with the ontogenetic increase in mandible size. Nevertheless, differences exist between the two mouse groups regarding the timing of histological maturation of the mandible, the localization of certain bone remodeling fields, the temporospatial patterns of morphological variation, and the organization into two main modules. The dissimilarities in the process of mandible growth between the two groups of mice become more evident around sexual maturity, and could arise from alterations that Robertsonian translocations may exert on genes involved in the bone remodeling mechanism. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

The effects of milking frequency on insulin-like growth factor I signaling within the mammary gland of dairy cows.

PubMed

Murney, R; Stelwagen, K; Wheeler, T T; Margerison, J K; Singh, K

2015-08-01

In dairy cows, short-term changes in milking frequency (MF) in early lactation have been shown to produce both an immediate and a long-term effect on milk yield. The effect of MF on milk yield is controlled locally within mammary glands and could be a function of changes in either number or activity of secretory mammary epithelial cells (MEC). Insulin-like growth factor I (IGF-I) signaling is one candidate factor that could mediate these effects, as it can be controlled locally within mammary glands. Both MEC number and activity can be affected by IGF-I signaling by activating the phosphoinositide 3-kinase (PI3K)/Akt and extracellular-signal-regulated kinase (ERK)1/2 pathways. To investigate the relationship between MF and IGF-I signaling, udder halves of 17 dairy cows were milked either 4 times a day (4×) or once a day (1×) for 14 d in early lactation. On d 14, between 3 and 5 h following milking, mammary biopsies were obtained from 10 cows from both udder halves, and changes in the expression of genes associated with IGF-I signaling and the activation of the PI3K/Akt and ERK1/2 pathways were measured. The mRNA abundance of IGF type I receptor, IGF binding protein (IGFBP)-3, and IGFBP-5 were lower following 4× milking relative to 1× milking. However, the mRNA abundance of IGF-I was not affected by MF. Both IGFBP3 and IGFBP5 are thought to inhibit IGF-I; therefore, decreases in their mRNA abundance may serve to stimulate the IGF-I signal in the 4×-milked mammary gland. The activation of PI3K/Akt pathway was lower in response to 4× milking relative to 1×, and the activation of the ERK1/2 was unaffected by MF, suggesting that they do not mediate the effects of MF. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Mammary duct ectasia: a cause of bloody nipple discharge.

PubMed Central

Leung, Alexander K. C.; Kao, C. Pion

2004-01-01

We report a 13-year-old girl with bloody nipple discharge as a result of mammary duct ectasia. Our patient is the second reported case of mammary duct ectasia in a pubertal girl. Images Figure 1 PMID:15101674

Metallothionein expression in canine and feline mammary and melanotic tumours.

PubMed

Dincer, Z; Jasani, B; Haywood, S; Mullins, J E; Fuentealba, I C

2001-01-01

Moderate to strong immunohistochemical metallothionein (MT) positivity (MT expression) is associated with a poor prognosis in some human tumours. The aim of this study was to determine MT expression in mammary tumours and cutaneous melanomas in dogs and cats. Canine (67) and feline (47) mammary tumours, and cutaneous melanomas (canine 40, feline 26) were immunolabelled with MT monoclonal antibody E9. The overall incidence of MT expression of these tumours was similar to that observed in various human neoplasms. However, a striking interspecies difference was detected. In dogs, MT expression occurred in 100% of benign and 57% of malignant mammary tumours. In cats, however, 30% of malignant mammary tumours expressed MT but benign mammary tumours and cases of fibroadenomatous hyperplasia did not. Moderate to strong MT immunoreactivity was detected in 30% of benign and 25% of malignant cutaneous melanomas in dogs, and in 6% of malignant melanomas in cats. The findings in feline mammary tumours resembled findings reported in human breast cancer, but the cause of tumour-associated MT expression is unknown. Studies are in progress to determine whether the MT state (apo [metal-free] or holo [metal-bound]) accounts for the paradoxical association of MT expression with individual types of tumours and the animal species in which they arise. Copyright Harcourt Publishers Ltd.

Increased Excitatory Synaptic Transmission of Dentate Granule Neurons in Mice Lacking PSD-95-Interacting Adhesion Molecule Neph2/Kirrel3 during the Early Postnatal Period.

PubMed

Roh, Junyeop D; Choi, Su-Yeon; Cho, Yi Sul; Choi, Tae-Yong; Park, Jong-Sil; Cutforth, Tyler; Chung, Woosuk; Park, Hanwool; Lee, Dongsoo; Kim, Myeong-Heui; Lee, Yeunkum; Mo, Seojung; Rhee, Jeong-Seop; Kim, Hyun; Ko, Jaewon; Choi, Se-Young; Bae, Yong Chul; Shen, Kang; Kim, Eunjoon; Han, Kihoon

2017-01-01

Copy number variants and point mutations of NEPH2 (also called KIRREL3 ) gene encoding an immunoglobulin (Ig) superfamily adhesion molecule have been linked to autism spectrum disorders, intellectual disability and neurocognitive delay associated with Jacobsen syndrome, but the physiological roles of Neph2 in the mammalian brain remain largely unknown. Neph2 is highly expressed in the dentate granule (DG) neurons of the hippocampus and is localized in both dendrites and axons. It was recently shown that Neph2 is required for the formation of mossy fiber filopodia, the axon terminal structure of DG neurons forming synapses with GABAergic neurons of CA3. In contrast, however, it is unknown whether Neph2 also has any roles in the postsynaptic compartments of DG neurons. We here report that, through its C-terminal PDZ domain-binding motif, Neph2 directly interacts with postsynaptic density (PSD)-95, an abundant excitatory postsynaptic scaffolding protein. Moreover, Neph2 protein is detected in the brain PSD fraction and interacts with PSD-95 in synaptosomal lysates. Functionally, loss of Neph2 in mice leads to age-specific defects in the synaptic connectivity of DG neurons. Specifically, Neph2 -/- mice show significantly increased spontaneous excitatory synaptic events in DG neurons at postnatal week 2 when the endogenous Neph2 protein expression peaks, but show normal excitatory synaptic transmission at postnatal week 3. The evoked excitatory synaptic transmission and synaptic plasticity of medial perforant pathway (MPP)-DG synapses are also normal in Neph2 -/- mice at postnatal week 3, further confirming the age-specific synaptic defects. Together, our results provide some evidence for the postsynaptic function of Neph2 in DG neurons during the early postnatal period, which might be implicated in neurodevelopmental and cognitive disorders caused by NEPH2 mutations.

From the Cover: Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants Decreased p-β-Cateninser675 Expression and Its Interaction With E-Cadherin in the Mammary Glands of Lactating Rats.

PubMed

Dianati, Elham; Wade, Michael G; Hales, Barbara F; Robaire, Bernard; Plante, Isabelle

2017-09-01

Proper mammary gland development and function require precise hormonal regulation and bidirectional cross talk between cells provided by means of paracrine factors as well as intercellular junctions; exposure to environmental endocrine disruptors can disturb these processes. Exposure to one such family of chemicals, the brominated flame retardants (BFRs), is ubiquitous. Here, we tested the hypothesis that BFR exposures disrupt signaling pathways and intercellular junctions that control mammary gland development. Before mating, during pregnancy and throughout lactation, female Sprague-Dawley rats were fed diets containing that BFR mixture based on house dust, delivering nominal exposures of BFR of 0 (control), 0.06, 20, or 60 mg/kg/d. Dams were euthanized and mammary glands collected on postnatal day 21. BFR exposure had no significant effects on mammary gland/body weight ratios or the levels of proteins involved in milk synthesis, epithelial-mesenchymal transition, cell-cell interactions, or hormone signalling. However, BFR exposure (0.06 mg/kg/d) down-regulated phospho-ser675 β-catenin (p-β-catSer675) levels in the absence of any effect on total β-catenin levels. Levels of p-CREB were also down-regulated, suggesting that PKA inhibition plays a role. p-β-catSer675 co-localized with β-catenin at the mammary epithelial cell membrane, and its expression was decreased in animals from the 0.06 and 20 mg/kg/d BFR treatment groups. Although β-Catenin signaling was not affected by BFR exposure, the interaction between p-β-catSer675 and E-cadherin was significantly reduced. Together, our results demonstrate that exposure to an environmentally relevant mixture of BFR during pregnancy and lactation decreases p-β-catser675 at cell adhesion sites, likely in a PKA-dependant manner, altering mammary gland signaling. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e

Is the organisation and structure of hospital postnatal care a barrier to quality care? Findings from a state-wide review in Victoria, Australia.

PubMed

McLachlan, Helen L; Forster, Della A; Yelland, Jane; Rayner, Joanne; Lumley, Judith

2008-09-01

to describe the structure and organisation of hospital postnatal care in Victoria, Australia. postal survey sent to all public hospitals in Victoria (n=71) and key-informant interviews with midwives and medical practitioners (n=38). Victoria, Australia. providers of postnatal care in Victorian public hospitals. there is significant diversity across Victoria in the way postnatal units are structured and organised and in the way care is provided. There are differences in numerous practices, including maternal and neonatal observations and the length of time women spend in hospital after giving birth. Although the benefits of continuity of care are recognised by health care providers, continuity is difficult to provide in the postnatal period. Postnatal care is provided in busy, sometimes chaotic environments, with many barriers to providing effective care and few opportunities for women to rest and recover after childbirth. The findings in this study can, in part, be explained by the lack of evidence that has been available to guide early postnatal care. current structures such as standard postnatal documentation (clinical pathways) and fixed length of stay, may inhibit rather than support individualised care for women after childbirth. There is a need to move towards greater flexibility in providing of early postnatal care, including alternative models of service delivery; choice and flexibility in the length of stay after birth; a focus on the individual with far less emphasis on care being structured around organisational requirements; and building an evidence base to guide care.

Accelerated onset of the vesicovesical reflex in postnatal NGF-OE mice and the role of neuropeptides

PubMed Central

Girard, Beatrice; Peterson, Abbey; Malley, Susan; Vizzard, Margaret A.

2016-01-01

The mechanisms underlying the postnatal maturation of micturition from a somatovesical to a vesicovesical reflex are not known but may involve neuropeptides in the lower urinary tract. A transgenic mouse model with chronic urothelial overexpression (OE) of NGF exhibited increased voiding frequency, increased number of non-voiding contractions, altered morphology and hyperinnervation of the urinary bladder by peptidergic (e.g., Sub P and CGRP) nerve fibers in the adult. In early postnatal and adult NGF-OE mice we have now examined: (1) micturition onset using filter paper void assays and open-outlet, continuous fill, conscious cystometry; (2) innervation and neurochemical coding of the suburothelial plexus of the urinary bladder using immunohistochemistry and semi-quantitative image analyses; (3) neuropeptide protein and transcript expression in urinary bladder of postnatal and adult NGF-OE mice using Q-PCR and ELISAs and (4) the effects of intravesical instillation of a neurokinin (NK)-1 receptor antagonist on bladder function in postnatal and adult NGF-OE mice using conscious cystometry. Postnatal NGF-OE mice exhibit age-dependent (R2= 0.996–0.998; p ≤ 0.01) increases in Sub and CGRP expression in the urothelium and significantly (p ≤ 0.01) increased peptidergic hyperinnervation of the suburothelial nerve plexus. By as early as P7, NGF-OE mice exhibit a vesicovesical reflex in response to intravesical instillation of saline whereas littermate WT mice require perigenital stimulation to elicit a micturition reflex until P13 when vesicovesical reflexes are first observed. Intravesical instillation of a NK-1 receptor antagonist, netupitant (0.1 μg/ml), significantly (p ≤ 0.01) increased void volume and the interval between micturition events with no effects on bladder pressure (baseline, threshold, peak) in postnatal NGF-OE mice; effects on WT mice were few. NGF-induced pleiotropic effects on neuropeptide (e.g., Sub P) expression in the urinary bladder

A Spectrum of Monoclonal Antibodies Reactive with Human Mammary Tumor Cells

NASA Astrophysics Data System (ADS)

Colcher, D.; Horan Hand, P.; Nuti, M.; Schlom, J.

1981-05-01

Splenic lymphocytes of mice, immunized with membrane-enriched fractions of metastatic human mammary carcinoma tissues, were fused with the NS-1 non-immunoglobulin-secreting murine myeloma cell line. This resulted in the generation of hybridoma cultures secreting immunoglobulins reactive in solid-phase radioimmunoassays with extracts of metastatic mammary carcinoma cells from involved livers, but not with extracts of apparently normal human liver. As a result of further screening of immunoglobulin reactivities and double cloning of cultures, 11 monoclonal antibodies were chosen that demonstrated reactivities with human mammary tumor cells and not with apparently normal human tissues. These monoclonal antibodies could be placed into at least five major groups on the basis of their differential binding to the surface of various live human mammary tumor cells in culture, to extracts of mammary tumor tissues, or to tissue sections of mammary tumor cells studied by the immunoperoxidase technique. Whereas a spectrum of reactivities to mammary tumors was observed with the 11 monoclonal antibodies, no reactivity was observed to apparently normal cells of the following human tissues: breast, lymph node, lung, skin, testis, kidney, thymus, bone marrow, spleen, uterus, thyroid, intestine, liver, bladder, tonsils, stomach, prostate, and salivary gland. Several of the antibodies also demonstrated a ``pancarcinoma'' reactivity, showing binding to selected non-breast carcinomas. None of the monoclonal antibodies showed binding to purified ferritin or carcinoembryonic antigen. Monoclonal antibodies of all five major groups, however, demonstrated binding to human metastatic mammary carcinoma cells both in axillary lymph nodes and at distal sites.

In vitro expansion of the mammary stem/progenitor cell population by xanthosinetreatment

USDA-ARS?s Scientific Manuscript database

Background: Mammary stem cells are critical for growth and maintenance of the mammary gland and therefore of considerable interest for improving productivity and efficiency of dairy animals. Xanthosine (Xs) treatment has been demonstrated to promote expansion of putative mammary stem cells in vivo ...

Pre- and Early-Postnatal Nutrition Modify Gene and Protein Expressions of Muscle Energy Metabolism Markers and Phospholipid Fatty Acid Composition in a Muscle Type Specific Manner in Sheep

PubMed Central

Hou, Lei; Kongsted, Anna H.; Ghoreishi, Seyed M.; Takhtsabzy, Tasnim K.; Friedrichsen, Martin; Hellgren, Lars I.; Kadarmideen, Haja N.; Vaag, Allan; Nielsen, Mette O.

2013-01-01

We previously reported that undernutrition in late fetal life reduced whole-body insulin sensitivity in adult sheep, irrespective of dietary exposure in early postnatal life. Skeletal muscle may play an important role in control of insulin action. We therefore studied a range of putative key muscle determinants of insulin signalling in two types of skeletal muscles (longissimus dorsi (LD) and biceps femoris (BF)) and in the cardiac muscle (ventriculus sinister cordis (VSC)) of sheep from the same experiment. Twin-bearing ewes were fed either 100% (NORM) or 50% (LOW) of their energy and protein requirements during the last trimester of gestation. From day-3 postpartum to 6-months of age (around puberty), twin offspring received a high-carbohydrate-high-fat (HCHF) or a moderate-conventional (CONV) diet, whereafter all males were slaughtered. Females were subsequently raised on a moderate diet and slaughtered at 2-years of age (young adults). The only long-term consequences of fetal undernutrition observed in adult offspring were lower expressions of the insulin responsive glucose transporter 4 (GLUT4) protein and peroxisome proliferator-activated receptor gamma, coactivator 1α (PGC1α) mRNA in BF, but increased PGC1α expression in VSC. Interestingly, the HCHF diet in early postnatal life was associated with somewhat paradoxically increased expressions in LD of a range of genes (but not proteins) related to glucose uptake, insulin signalling and fatty acid oxidation. Except for fatty acid oxidation genes, these changes persisted into adulthood. No persistent expression changes were observed in BF and VSC. The HCHF diet increased phospholipid ratios of n-6/n-3 polyunsaturated fatty acids in all muscles, even in adults fed identical diets for 1½ years. In conclusion, early postnatal, but not late gestation, nutrition had long-term consequences for a number of determinants of insulin action and metabolism in LD. Tissues other than muscle may account for reduced whole

Mammary blood flow regulation in the nursing rabbit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katz, M.; Creasy, R.K.

Cardiac output and mammary blood flow distribution prior to and after suckling were studied in 10 nursing rabbits by means of radionuclide-labeled microspheres. Suckling was followed by a 5.8% rise in cardiac output and a 20.4% rise in mammary blood flow. Determinations of intraglandular blood flow distribution have shown that there was a 43% increase in blood flow to the glands suckled from as compared to a 22.7% rise to the contralateral untouched glands and a 4.9% rise in the remainder of untouched glands. The conclusion is that a local mechanism may be involved in the regulation of mammary bloodmore » flow in the nursing rabbit.« less

Mammary stem cells have myoepithelial cell properties

PubMed Central

Prater, Michael D.; Petit, Valérie; Russell, I. Alasdair; Giraddi, Rajshekhar; Shehata, Mona; Menon, Suraj; Schulte, Reiner; Kalajzic, Ivo; Rath, Nicola; Olson, Michael F.; Metzger, Daniel; Faraldo, Marisa M.; Deugnier, Marie-Ange; Glukhova, Marina A.; Stingl, John

2014-01-01

Contractile myoepithelial cells dominate the basal layer of the mammary epithelium and are considered to be differentiated cells. However, we observe that up to 54% of single basal cells can form colonies when seeded into adherent culture in the presence of agents that disrupt acin-myosin interactions, and on average, 65% of the single-cell-derived basal colonies can repopulate a mammary gland when transplanted in vivo. This indicates that a high proportion of basal myoepithelial cells can give rise to a mammary repopulating unit (MRU). We demonstrate that myoepithelial cells, flow-sorted using 2 independent myoepithelial-specific reporter strategies, have MRU capacity. Using an inducible lineage tracing approach we follow the progeny of α-smooth muscle actin-expressing myoepithelial cells and show that they function as long-lived lineage-restricted stem cells in the virgin state and during pregnancy. PMID:25173976

Bovine mammary stem cells: Cell biology meets production agriculture

USDA-ARS?s Scientific Manuscript database

Mammary stem cells (MaSC) provide for net growth, renewal and turnover of mammary epithelial cells, and are therefore potential targets for strategies to increase production efficiency. Appropriate regulation of MaSC can potentially benefit milk yield, persistency, dry period management and tissue ...

Sebaceous gland carcinoma and mammary gland carcinoma in an African hedgehog (Ateletrix albiventris).

PubMed

Matute, Alonso Reyes; Bernal, Adriana Mendez; Lezama, José Ramírez; Guadalupe, Manzano Pech Linaloe; Antonio, Galicia Avalos Marco

2014-09-01

A sebaceous carcinoma was diagnosed, together with a mammary carcinoma, in an adult African hedgehog (Atelerix albiventris). The first neoplasm was located in the subcutaneous tissue of the neck and extended towards the axillary area of the chest. The second was located in the subcutaneous left caudal abdominal region. The purpose of this paper is to report the histopathologic and ultrastructural features of these neoplasms. Although there is little information about diseases affecting this species, it is known that neoplastic disorders are fairly common in African hedgehogs. The mammary carcinoma is considered to be the most common neoplasm in these animals; however, the presentation of sebaceous carcinoma is rare. In hedgehogs, the simultaneous presence of two neoplasms is common, which is why special attention should be paid to the presentation of other tumors during the early detection of a neoplastic process as this will greatly facilitate the optimal treatment and improve the long-term prognosis of affected animals.

Six1 expands the mouse mammary epithelial stem/progenitor cell pool and induces mammary tumors that undergo epithelial-mesenchymal transition

PubMed Central

McCoy, Erica L.; Iwanaga, Ritsuko; Jedlicka, Paul; Abbey, Nee-Shamo; Chodosh, Lewis A.; Heichman, Karen A.; Welm, Alana L.; Ford, Heide L.

2009-01-01

Six1 is a developmentally regulated homeoprotein with limited expression in most normal adult tissues and frequent misexpression in a variety of malignancies. Here we demonstrate, using a bitransgenic mouse model, that misexpression of human Six1 in adult mouse mammary gland epithelium induces tumors of multiple histological subtypes in a dose-dependent manner. The neoplastic lesions induced by Six1 had an in situ origin, showed diverse differentiation, and exhibited progression to aggressive malignant neoplasms, as is often observed in human carcinoma of the breast. Strikingly, the vast majority of Six1-induced tumors underwent an epithelial-mesenchymal transition (EMT) and expressed multiple targets of activated Wnt signaling, including cyclin D1. Interestingly, Six1 and cyclin D1 coexpression was found to frequently occur in human breast cancers and was strongly predictive of poor prognosis. We further show that Six1 promoted a stem/progenitor cell phenotype in the mouse mammary gland and in Six1-driven mammary tumors. Our data thus provide genetic evidence for a potent oncogenic role for Six1 in mammary epithelial neoplasia, including promotion of EMT and stem cell–like features. PMID:19726883

A qualitative study of the acceptability of routine screening of postnatal women using the Edinburgh Postnatal Depression Scale.

PubMed Central

Shakespeare, Judy; Blake, Fiona; Garcia, Jo

2003-01-01

BACKGROUND: Screening for postnatal depression using the Edinburgh Postnatal Depression Scale (EPDS) has been widely recommended and implemented in primary care, although little is known about how acceptable it is to women. AIM: To explore the acceptability to women of postnatal screening by health visitors with the EPDS. DESIGN OF STUDY: Qualitative interview study. SETTING: Postnatal patients from 22 general practices within the area of Oxford City Primary Care Group. METHOD: Thirty-nine postnatal women from a purposive sample were interviewed, chosen on the basis of different general practices, EPDS results at eight weeks and eight months postnatal, and whether 'listening visits' were received. The interviews were analysed using the constant comparative method. RESULTS: Just over half of the women interviewed found screening with the EPDS less than acceptable, whatever their postnatal emotional health. The main themes identified were problems with the process of screening and, in particular, the venue, the personal intrusion of screening and stigma. The women interviewed had a clear preference for talking about how they felt, rather than filling out a questionnaire. CONCLUSION: For this sample, routine screening with the EPDS was less than acceptable for the majority of women. This is of concern, as universal screening with the EPDS for the detection of postnatal depression is already recommended and widespread in primary care. PMID:14601337

Bisphenol S Alters the Lactating Mammary Gland and Nursing Behaviors in Mice Exposed During Pregnancy and Lactation.

PubMed

LaPlante, Charlotte D; Catanese, Mary C; Bansal, Ruby; Vandenberg, Laura N

2017-10-01

High doses of estrogenic pharmaceuticals were once prescribed to women to halt lactation. Yet, the effects of low-level xenoestrogens on lactation remain poorly studied. We investigated the effects of bisphenol S (BPS), an estrogen receptor (ER) agonist, on the lactating mammary gland; the arcuate nucleus, a region of the hypothalamus important for neuroendocrine control of lactational behaviors; and nursing behavior in CD-1 mice. Female mice were exposed to vehicle, 2 or 200 µg BPS/kg/d from pregnancy day 9 until lactational day (LD) 20, and tissues were collected on LD21. Tissues were also collected from a second group at LD2. BPS exposure significantly reduced the fraction of the mammary gland comprised of lobules, the milk-producing units, on LD21, but not LD2. BPS also altered expression of Esr1 and ERα in the mammary gland at LD21, consistent with early involution. In the arcuate nucleus, no changes were observed in expression of signal transducer and activator of transcription 5, a marker of prolactin signaling, or ERα, suggesting that BPS may act directly on the mammary gland. However, observations of nursing behavior collected during the lactational period revealed stage-specific effects on both pup and maternal nursing behaviors; BPS-treated dams spent significantly more time nursing later in the lactational period, and BPS-treated pups were less likely to initiate nursing. Pup growth and development were also stunted. These data indicate that low doses of BPS can alter lactational behaviors and the maternal mammary gland. Together, they support the hypothesis that pregnancy and lactation are sensitive to low-dose xenoestrogen exposures. Copyright © 2017 Endocrine Society.

Keratinocyte growth factor is a growth factor for mammary epithelium in vivo. The mammary epithelium of lactating rats is resistant to the proliferative action of keratinocyte growth factor.

PubMed Central

Ulich, T. R.; Yi, E. S.; Cardiff, R.; Yin, S.; Bikhazi, N.; Biltz, R.; Morris, C. F.; Pierce, G. F.

1994-01-01

Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor (FGF) family. KGF is secreted by stromal cells and affects epithelial but not mesenchymal cell proliferation. KGF injected intravenously was found to cause dramatic proliferation of mammary epithelium in the mammary glands of rats. KGF causes ductal neogenesis and intraductal epithelial hyperplasia but not lobular differentiation in nulliparous female rats. KGF causes ductal and lobular epithelial hyperplasia in male rats. KGF causes proliferation of ductal and acinar cells in the mammary glands of pregnant rats. On the other hand, the ductal epithelium of lactating postpartum rats is resistant to the proliferative action of KGF. The mammary glands of lactating rats did not express less KGF receptor mRNA than the glands of pregnant rats, suggesting that the resistance of the ductal epithelium to KGF during lactation is not related to KGF receptor mRNA down-regulation. The mammary glands of both pregnant and postpartum lactating rats express KGF mRNA with more KGF present in the glands of lactating rats. In conclusion, the KGF and KGF receptor genes are expressed in rat mammary glands and recombinant KGF is a potent growth factor for mammary epithelium. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8178937

Offspring psychopathology following preconception, prenatal, and postnatal maternal bereavement stress

PubMed Central

Class, Quetzal A.; Abel, Kathryn M.; Khashan, Ali S.; Rickert, Martin E.; Dalman, Christina; Larsson, Henrik; Hultman, Christina M.; Långström, Niklas; Lichtenstein, Paul; D’Onofrio, Brian M.

2013-01-01

Background Preconception, prenatal, and postnatal maternal stress are associated with increased offspring psychopathology, but findings are inconsistent and need replication. We estimated associations between maternal bereavement stress and offspring autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, suicide attempt, and completed suicide. Methods Using Swedish registers, we conducted the largest population-based study to date examining associations between stress exposure in 738,144 offspring born 1992–2000 for childhood outcomes and 2,155,221 offspring born 1973–1997 for adult outcomes with follow-up through 2009. Maternal stress was defined as death of a first degree relative during 6 months before conception, across pregnancy, or the first two postnatal years. Cox proportional survival analyses were used to obtain hazard ratios (HR) in unadjusted and adjusted analyses. Results Marginal increased risk of bipolar disorder and schizophrenia following preconception bereavement stress was not significant. Third trimester prenatal stress increased risk of ASD (adjusted HR=1.58, 95% CI: 1.15–2.17) and ADHD (adjusted HR=1.31, 95% CI: 1.04–1.66). First postnatal year stress increased risk for offspring suicide attempt (adjusted HR=1.13, 95% CI: 1.02–1.25) and completed suicide (adjusted HR=1.51, 95% CI: 1.08–2.11). Bereavement stress during the second postnatal year increased risk of ASD (adjusted HR=1.30, 95% CI: 1.09–1.55). Conclusions Further research is needed on associations between preconception stress and psychopathological outcomes. Prenatal bereavement stress increases risk of offspring ASD and ADHD. Postnatal bereavement stress moderately increases risk of offspring suicide attempt, completed suicide, and ASD. Smaller previous studies may have overestimated associations between early stress and psychopathological outcomes. PMID:23591021

Isolation of Endoplasmic Reticulum Fractions from Mammary Epithelial Tissue.

PubMed

Chanat, Eric; Le Parc, Annabelle; Lahouassa, Hichem; Badaoui, Bouabid

2016-06-01

In the mammary glands of lactating animals, the mammary epithelial cells that surround the lumen of the acini produce and secrete copious amounts of milk. Functional differentiation of these mammary epithelial cells depends on the development of high-efficiency secretory pathways, notably for protein and lipid secretion. Protein secretion is a fundamental process common to all animal cells that involves a subset of cellular organelles, including the endoplasmic reticulum and the Golgi apparatus. In contrast, en masse secretion of triglycerides and cholesterol esters in the form of milk fat globules is a unique feature of the mammary epithelial cell. Cytoplasmic lipid droplets, the intracellular precursors of milk fat globules, originate from the endoplasmic reticulum, as do most milk-specific proteins. This organelle is therefore pivotal in the biogenesis of milk components. Fractionation of the cell into its subcellular parts is an approach that has proven very powerful for understanding organelle function and for studying the specific role of an organelle in a given cell activity. Here we describe a method for the purification of both smooth and rough microsomes, the membrane-bound endoplasmic reticulum fragments that form from endoplasmic reticulum domains when cells are broken up, from mammary gland tissue at lactation.

Exploratory behavior in rats postnatally exposed to cocaine and housed in an enriched environment.

PubMed

Magalhães, Ana; Melo, Pedro; Alves, Cecília Juliana; Tavares, Maria Amélia; de Sousa, Liliana; Summavielle, Teresa

2008-10-01

Exposure to cocaine in early periods of postnatal life is usually associated with changes in development of neurotransmitter systems and structure of the central nervous system. Such changes are most likely correlated with behavioral alterations. Environmental enrichment conditions (EC) in early stages is a factor that affects structural and behavioral development. The purpose of this study is to examine the effects of EC on rats postnatally exposed to cocaine on exploratory behavior. Wistar rats were assigned to four groups-Group 1: pups exposed to cocaine hydrochloride (15 mg/kg body weight/day) s.c., in two daily doses, from postnatal day (PND) 1 to 28 and reared in EC; Group 2: pups exposed to cocaine as previously described and reared in a standard environmental conditions (SC); Group 3: pups saline-injected and reared in EC; and Group 4: pups saline-injected and reared in SC. On PND 21, 24, and 28, groups of four rats (to reduce anxiety) were placed for 10 minutes into an arena with several objects. The following exploratory behavioral categories were examined: object interaction, exploration, manipulation, approximation, and total time of object contact. Animals from Group 2 showed decreased object interaction and total contact on PND 21. Control offspring reared in EE showed decreases in exploratory behavior at all ages analyzed compared with the control SE group, while cocaine-exposed animals reared in EC showed decreased object interaction, object approximation, and total exploratory behavior. The results in this group suggest that EC improved information acquisition and memory processes in animals postnatally exposed to cocaine.

Early and late outcome of skeletonised bilateral internal mammary arteries anastomosed to the left coronary system.

PubMed

Bonacchi, M; Battaglia, F; Prifti, E; Leacche, M; Nathan, N S; Sani, G; Popoff, G

2005-02-01

To investigate in a retrospective study the technical aspects of using the in situ bilateral internal mammary arteries (IMAs), with the right IMA (RIMA) used for revascularisation of the circumflex system, and to evaluate early and late outcome. Between January 1997 and July 2003, 552 consecutive patients underwent grafting of the circumflex artery system with an in situ skeletonised RIMA routed through the transverse sinus (eventually retrocaval). Mean (SD) age was 63.8 (11) years. 331 (60%) patients underwent total arterial myocardial revascularisation. Mean follow up was 26 (9) months. The success rate of skeletonised RIMA grafting to the circumflex branch was 100%. There were 19 (3.4%) in-hospital deaths. Perioperative myocardial infarction occurred in 12 (2.2%) patients. In 155 patients undergoing postoperative angiography, two had an occluded RIMA and a string-like phenomenon was seen in three RIMA and one left IMA (LIMA). Three RIMA and three LIMA had stenotic lesions. The patency rates of RIMA and LIMA were 94% and 97.4%, respectively. Strong predictors of non-functional IMA grafts were a recipient coronary artery diameter of < 1.5 mm (p = 0.022), < 60% stenosis of the recipient coronary artery (p = 0.015), diffuse stenotic lesions of the recipient coronary artery (p = 0.018), and a small IMA calibre (p = 0.0001). Cumulative actuarial survival at three years was 96.4% and event-free cumulative survival was 93.8%. Use of the bilateral IMAs offers the possibility of constructing various configurations, making total arterial myocardial revascularisation possible with a minimum number of arterial conduits. Use of the skeletonised RIMA through the transverse sinus and eventually retrocavally can reach most branches of the circumflex system and is associated with an excellent patency rate. Patients who received bilateral IMA grafts for left coronary system revascularisation had improved early and late outcomes and decreased risk of death, reoperation, and

Autocrine-paracrine regulation of the mammary gland.

PubMed

Weaver, S R; Hernandez, L L

2016-01-01

The mammary gland has a remarkable capacity for regulation at a local level, particularly with respect to its main function: milk secretion. Regulation of milk synthesis has significant effects on animal and human health, at the level of both the mother and the neonate. Control by the mammary gland of its essential function, milk synthesis, is an evolutionary necessity and is therefore tightly regulated at a local level. For at least the last 60 yr, researchers have been interested in elucidating the mechanisms underpinning the mammary gland's ability to self-regulate, largely without the influence from systemic hormones or signals. By the 1960s, scientists realized the importance of milk removal in the capacity of the gland to produce milk and that the dynamics of this removal, including emptying of the alveolar spaces and frequency of milking, were controlled locally as opposed to traditional systemic hormonal regulation. Using both in vitro systems and various mammalian species, including goats, marsupials, humans, and dairy cows, it has been demonstrated that the mammary gland is largely self-regulating in its capacity to support the young, which is the evolutionary basis for milk production. Local control occurs at the level of the mammary epithelial cell through pressure and stretching negative-feedback mechanisms, and also in an autocrine fashion through bioactive factors within the milk which act as inhibitors, regulating milk secretion within the alveoli themselves. It is only within the last 20 to 30 yr that potential candidates for these bioactive factors have been examined at a molecular level. Several, including parathyroid hormone-related protein, growth factors (transforming growth factor, insulin-like growth factor, epidermal growth factor), and serotonin, are synthesized within and act upon the gland and possess dynamic receptor activity resulting in diverse effects on growth, calcium homeostasis, and milk composition. This review will focus on the

Identification of depression in women during pregnancy and the early postnatal period using the Whooley questions and the Edinburgh Postnatal Depression Scale: protocol for the Born and Bred in Yorkshire: PeriNatal Depression Diagnostic Accuracy (BaBY PaNDA) study.

PubMed

Littlewood, Elizabeth; Ali, Shehzad; Ansell, Pat; Dyson, Lisa; Gascoyne, Samantha; Hewitt, Catherine; Keding, Ada; Mann, Rachel; McMillan, Dean; Morgan, Deborah; Swan, Kelly; Waterhouse, Bev; Gilbody, Simon

2016-06-13

Perinatal depression is well recognised as a mental health condition but <50% of cases are identified by healthcare professionals in routine clinical practice. The Edinburgh Postnatal Depression Scale (EPDS) is often used to detect symptoms of postnatal depression in maternity and child services. The National Institute for Health and Care Excellence (NICE) recommends 2 'ultra-brief' case-finding questions (the Whooley questions) to aid identification of depression during the perinatal period, but this recommendation was made in the absence of any validation studies in a perinatal population. Limited research exists on the acceptability of these depression case-finding instruments and the cost-effectiveness of routine screening for perinatal depression. The diagnostic accuracy of the Whooley questions and the EPDS will be determined against a reference standard (the Client Interview Schedule-Revised) during pregnancy (around 20 weeks) and the early postnatal period (around 3-4 months post partum) in a sample of 379 women. Further outcome measures will assess a range of psychological comorbidities, health-related quality of life and resource utilisation. Women will be followed up 12 months postnatally. The sensitivity, specificity and predictive values of the Whooley questions and the EPDS will be calculated against the reference standard at 20 weeks pregnancy and 3-4 months post partum. Acceptability of the depression case-finding instruments to women and healthcare professionals will involve in-depth qualitative interviews. An existing decision analytic model will be adapted to determine the cost-effectiveness of routine screening for perinatal depression. This study is considered low risk for participants. Robust protocols will deal with cases where risk of depression, self-harm or suicide is identified. The protocol received favourable ethical opinion from the North East-York Research Ethics Committee (reference: 11/NE/0022). The study findings will be

Low dose bisphenol S or ethinyl estradiol exposures during the perinatal period alter female mouse mammary gland development.

PubMed

Kolla, SriDurgaDevi; Morcos, Mary; Martin, Brian; Vandenberg, Laura N

2018-03-08

Throughout life, mammary tissue is strongly influenced by hormones. Scientists have hypothesized that synthetic chemicals with hormonal activities could disrupt mammary gland development and contribute to breast diseases and dysfunction. Bisphenol S (BPS) is an estrogenic compound used in many consumer products. In this study, CD-1 mice were exposed to BPS (2 or 200 μg/kg/day) during pregnancy and lactation. Mice exposed to 0.01 or 1 μg/kg/day ethinyl estradiol (EE2), a pharmaceutical estrogen, were also evaluated. Mammary glands from female offspring were collected prior to the onset of puberty, during puberty, and in early adulthood. Growth parameters, histopathology, cell proliferation and expression of hormone receptors were quantified. Our evaluations revealed age- and dose-specific effects of BPS that were different from the effects of EE2, and distinct from the effects of BPA that have been reported previously. These assessments suggest that individual xenoestrogens may have unique effects on this sensitive tissue. Copyright © 2018 Elsevier Inc. All rights reserved.

Fish consumption in pregnancy and omega-3 status after birth are not associated with postnatal depression.

PubMed

Browne, Joanna C; Scott, Kate M; Silvers, Karen M

2006-02-01

Research to date suggests a relationship between fish consumption, omega-3 polyunsaturated fatty acids, and depression. However, interpretation of this research is difficult due to methodological limitations. Postpartum women provide an excellent opportunity to examine these relationships because omega-3s are transferred from mother to fetus during pregnancy and from mother to child after birth through breast milk. Hence new mothers are more likely to be depleted in omega-3s. Our aim was to determine whether prenatal fish consumption and omega-3 status after birth were associated with postnatal depression. Eighty first-time mothers were recruited; 41 who scored on or over the cut-off on one of two depression-screening instruments, and 39 in the control group. Depression was diagnosed using the Composite International Diagnostic Interview. Fish consumption was measured during pregnancy, and depression and omega-3 status were determined postnatally. Logistic regression and t-tests were used to examine relationships between fish consumption, omega-3 status, and postnatal depression, while controlling for known covariates. Prenatal fish consumption was not predictive of postnatal depression, and postnatal omega-3 status was not associated with postnatal depression. However, prenatal fish consumption did predict omega-3 status after birth. Prenatal fish consumption was measured using only a food frequency questionnaire, and no participants consumed oily fish (rich in omega-3s) regularly. There was no association between postnatal depression and either fish consumption in early pregnancy, or omega-3 status after birth. Our findings make it difficult to justify trials of omega-3 polyunsaturated fatty acids in the treatment of postnatal depression.

Prenatal and postnatal stress and asthma in children: Temporal- and sex-specific associations.

PubMed

Lee, Alison; Mathilda Chiu, Yueh-Hsiu; Rosa, Maria José; Jara, Calvin; Wright, Robert O; Coull, Brent A; Wright, Rosalind J

2016-09-01

Temporal- and sex-specific effects of perinatal stress have not been examined for childhood asthma. We examined associations between prenatal and/or postnatal stress and children's asthma (n = 765) and effect modification by sex in a prospective cohort study. Maternal negative life events were ascertained prenatally and postpartum. Negative life event scores were categorized as 0, 1 to 2, 3 to 4, or 5 or greater to assess exposure-response relationships. We examined effects of prenatal and postnatal stress on children's asthma by age 6 years, modeling each as independent predictors, mutually adjusting for prenatal and postnatal stress, and finally considering interactions between prenatal and postnatal stress. Effect modification by sex was examined in stratified analyses and by fitting interaction terms. When considering stress in each period independently, among boys, a dose-response relationship was evident for each level increase on the ordinal scale prenatally (odds ratio [OR], 1.38; 95% CI, 1.06-1.79; P value for trend = .03) and postnatally (OR, 1.53; 95% CI, 1.16-2.01; P value for trend = .001); among girls, only the postnatal trend was significant (OR, 1.60; 95% CI, 1.14-2.22; P value for trend = .005). Higher stress in both the prenatal and postnatal periods was associated with increased odds of receiving a diagnosis of asthma in girls (OR, 1.37; 95% CI, 0.98-1.91; Pinteraction = .07) but not boys (OR, 1.08; 95% CI, 0.82-1.42; Pinteraction = .61). Although boys were more vulnerable to stress during the prenatal period, girls were more affected by postnatal stress and cumulative stress across both periods in relation to asthma. Understanding sex and temporal differences in response to early-life stress might provide unique insight into the cause and natural history of asthma. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

MRI ductography of contrast agent distribution and leakage in normal mouse mammary ducts and ducts with in situ cancer.

PubMed

Markiewicz, Erica; Fan, Xiaobing; Mustafi, Devkumar; Zamora, Marta; Conzen, Suzanne D; Karczmar, Gregory S

2017-07-01

High resolution 3D MRI was used to study contrast agent distribution and leakage in normal mouse mammary glands and glands containing in situ cancer after intra-ductal injection. Five female FVB/N mice (~19weeks old) with no detectable mammary cancer and eight C3(1) SV40 Tag virgin female mice (~15weeks old) with extensive in situ cancer were studied. A 34G, 45° tip Hamilton needle with a 25μL Hamilton syringe was inserted into the tip of the nipple and approximately 15μL of a Gadodiamide was injected slowly over 1min into the nipple and throughout the duct on one side of the inguinal gland. Following injection, the mouse was placed in a 9.4T MRI scanner, and a series of high resolution 3D T1-weighted images was acquired with a temporal resolution of 9.1min to follow contrast agent leakage from the ducts. The first image was acquired at about 12min after injection. Ductal enhancement regions detected in images acquired between 12 and 21min after contrast agent injection was five times smaller in SV40 mouse mammary ducts (p<0.001) than in non-cancerous FVB/N mouse mammary ducts, perhaps due to rapid washout of contrast agent from the SV40 ducts. The contrast agent washout rate measured between 12min and 90min after injection was ~20% faster (p<0.004) in SV40 mammary ducts than in FVB/N mammary ducts. These results may be due to higher permeability of the SV40 ducts, likely due to the presence of in situ cancers. Therefore, increased permeability of ducts may indicate early stage breast cancers. Copyright © 2017 Elsevier Inc. All rights reserved.

S-adenosyl methionine prevents ASD like behaviors triggered by early postnatal valproic acid exposure in very young mice.

PubMed

Ornoy, Asher; Weinstein-Fudim, Liza; Tfilin, Matanel; Ergaz, Zivanit; Yanai, Joseph; Szyf, Moshe; Turgeman, Gadi

2018-01-16

A common animal model of ASD is the one induced by valproic acid (VPA), inducing epigenetic changes and oxidative stress. We studied the possible preventive effect of the methyl donor for epigenetic enzymatic reactions, S-adenosine methionine (SAM), on ASD like behavioral changes and on redox potential in the brain and liver in this model. ICR albino mice were injected on postnatal day 4 with one dose of 300 mg/kg of VPA, with normal saline (controls) or with VPA and SAM that was given orally for 3 days at the dose of 30 mg/kg body weight. From day 50, we carried out neurobehavioral tests and assessment of the antioxidant status of the prefrontal cerebral cortex, liver assessing SOD and CAT activity, lipid peroxidation and the expression of antioxidant genes. Mice injected with VPA exhibited neurobehavioral deficits typical of ASD that were more prominent in males. Changes in the activity of SOD and CAT increased lipid peroxidation and changes in the expression of antioxidant genes were observed in the prefrontal cortex of VPA treated mice, more prominent in females, while ASD like behavior was more prominent in males. There were no changes in the redox potential of the liver. The co-administration of VPA and SAM alleviated most ASD like neurobehavioral symptoms and normalized the redox potential in the prefrontal cortex. Early postnatal VPA administration induces ASD like behavior that is more severe in males, while the redox status changes are more severe in females; SAM corrects both. VPA-induced ASD seems to result from epigenetic changes, while the redox status changes may be secondary. Copyright © 2018. Published by Elsevier Inc.

Prevention of mammary carcinogenesis by short-term estrogen and progestin treatments

PubMed Central

Rajkumar, Lakshmanaswamy; Guzman, Raphael C; Yang, Jason; Thordarson, Gudmundur; Talamantes, Frank; Nandi, Satyabrata

2004-01-01

Introduction Women who have undergone a full-term pregnancy before the age of 20 have one-half the risk of developing breast cancer compared with women who have never gone through a full-term pregnancy. This protective effect is observed universally among women of all ethnic groups. Parity in rats and mice also protects them against chemically induced mammary carcinogenesis. Methods Seven-week-old virgin Lewis rats were given N-methyl-N-nitrosourea. Two weeks later the rats were treated with natural or synthetic estrogens and progestins for 7–21 days by subcutaneous implantation of silastic capsules. Results In our current experiment, we demonstrate that short-term sustained exposure to natural or synthetic estrogens along with progestins is effective in preventing mammary carcinogenesis in rats. Treatment with 30 mg estriol plus 30 mg progesterone for 3 weeks significantly reduced the incidence of mammary cancer. Short-term exposure to ethynyl estradiol plus megesterol acetate or norethindrone was effective in decreasing the incidence of mammary cancers. Tamoxifen plus progesterone treatment for 3 weeks was able to confer only a transient protection from mammary carcinogenesis, while 2-methoxy estradiol plus progesterone was effective in conferring protection against mammary cancers. Conclusions The data obtained in the present study demonstrate that, in nulliparous rats, long-term protection against mammary carcinogenesis can be achieved by short-term treatments with natural or synthetic estrogen and progesterone combinations. PMID:14680498

Maternal deprivation decelerates postnatal morphological lung development of F344 rats.

PubMed

Hupa, Katharina Luise; Schmiedl, Andreas; Pabst, Reinhard; Von Hörsten, Stephan; Stephan, Michael

2014-02-01

Intensive medical care at premature born infants is often associated with separation of neonates from their mothers. Here, early artificial prolonged separation of rat pups from their dams (Maternal Deprivation, MD) was used to study potential impact on morphological lung maturation. Furthermore, we investigated the influence of an endogenous deficiency of the neuropeptide-cleaving dipeptidyl peptidase IV (DPP4), since the effects of MD are known to be partly mediated via neuropeptidergic effects, hypothesizing that MD will lead to a retardation of postnatal lung development, DPP4-dependendly. We used wild type and CD26/DPP4 deficient rats. For MD, the dam was placed each day into a separate cage for 2 h, while the pups remained in the nest on their own. Morphological lung maturation and cell proliferation at the postnatal days 7, 10, 14, and 21 were determined morphometrically. Maternally deprived wild types showed a retarded postnatal lung development compared with untreated controls in both substrains. During alveolarization, an increased thickness of alveolar septa and a decreased surface of septa about 50% were found. At the end of the morphological lung maturation, the surface of the alveolar septa was decreased at about 25% and the septal thickness remained increased about 20%. The proliferation rate was also decreased about 50% on day 14. However, the MD induced effects were less pronounced in DPP4-deficient rats, due to a significant deceleration already induced by DPP4-deficiency. Thus, MD as a model for postnatal stress experience influences remarkably postnatal development of rats, which is significantly modulated by the DPP4-system. Copyright © 2013 Wiley Periodicals, Inc.

Temporary Depletion of Microglia during the Early Postnatal Period Induces Lasting Sex-Dependent and Sex-Independent Effects on Behavior in Rats

PubMed Central

2016-01-01

Abstract Microglia are the primary immune cells of the brain and function in multiple ways to facilitate proper brain development. However, our current understanding of how these cells influence the later expression of normal behaviors is lacking. Using the laboratory rat, we administered liposomal clodronate centrally to selectively deplete microglia in the developing postnatal brain. We then assessed a range of developmental, juvenile, and adult behaviors. Liposomal clodronate treatment on postnatal days 0, 2, and 4 depleted microglia with recovery by about 10 days of age and induced a hyperlocomotive phenotype, observable in the second postnatal week. Temporary microglia depletion also increased juvenile locomotion in the open field test and decreased anxiety-like behaviors in the open field and elevated plus maze. These same rats displayed reductions in predator odor–induced avoidance behavior, but increased their risk assessment behaviors compared with vehicle-treated controls. In adulthood, postnatal microglia depletion resulted in significant deficits in male-specific sex behaviors. Using factor analysis, we identified two underlying traits—behavioral disinhibition and locomotion—as being significantly altered by postnatal microglia depletion. These findings further implicate microglia as being critically important to the development of juvenile and adult behavior. PMID:27957532

DNMT1 is essential for mammary and cancer stem cell maintenance and tumorigenesis

PubMed Central

Pathania, Rajneesh; Ramachandran, Sabarish; Elangovan, Selvakumar; Padia, Ravi; Yang, Pengyi; Cinghu, Senthilkumar; Veeranan-Karmegam, Rajalakshmi; Arjunan, Pachiappan; Gnana-Prakasam, Jaya P.; Fulzele, Sadanand; Pei, Lirong; Chang, Chang-Sheng; Choi, Hyeon; Shi, Huidong; Manicassamy, Santhakumar; Prasad, Puttur D.; Sharma, Suash; Ganapathy, Vadivel; Jothi, Raja; Thangaraju, Muthusamy

2015-01-01

Mammary stem/progenitor cells (MaSCs) maintain self-renewal of the mammary epithelium during puberty and pregnancy. DNA methylation provides a potential epigenetic mechanism for maintaining cellular memory during self-renewal. Although DNA methyltransferases (DNMTs) are dispensable for embryonic stem cell maintenance, their role in maintaining MaSCs and cancer stem cells (CSCs) in constantly replenishing mammary epithelium is unclear. Here we show that DNMT1 is indispensable for MaSC maintenance. Furthermore, we find that DNMT1 expression is elevated in mammary tumors, and mammary gland-specific DNMT1 deletion protects mice from mammary tumorigenesis by limiting the CSC pool. Through genome-scale methylation studies, we identify ISL1 as a direct DNMT1 target, hypermethylated and downregulated in mammary tumors and CSCs. DNMT inhibition or ISL1 expression in breast cancer cells limits CSC population. Altogether, our studies uncover an essential role for DNMT1 in MaSC and CSC maintenance and identify DNMT1-ISL1 axis as a potential therapeutic target for breast cancer treatment. PMID:25908435

DNMT1 is essential for mammary and cancer stem cell maintenance and tumorigenesis.

PubMed

Pathania, Rajneesh; Ramachandran, Sabarish; Elangovan, Selvakumar; Padia, Ravi; Yang, Pengyi; Cinghu, Senthilkumar; Veeranan-Karmegam, Rajalakshmi; Arjunan, Pachiappan; Gnana-Prakasam, Jaya P; Sadanand, Fulzele; Pei, Lirong; Chang, Chang-Sheng; Choi, Jeong-Hyeon; Shi, Huidong; Manicassamy, Santhakumar; Prasad, Puttur D; Sharma, Suash; Ganapathy, Vadivel; Jothi, Raja; Thangaraju, Muthusamy

2015-04-24

Mammary stem/progenitor cells (MaSCs) maintain self-renewal of the mammary epithelium during puberty and pregnancy. DNA methylation provides a potential epigenetic mechanism for maintaining cellular memory during self-renewal. Although DNA methyltransferases (DNMTs) are dispensable for embryonic stem cell maintenance, their role in maintaining MaSCs and cancer stem cells (CSCs) in constantly replenishing mammary epithelium is unclear. Here we show that DNMT1 is indispensable for MaSC maintenance. Furthermore, we find that DNMT1 expression is elevated in mammary tumours, and mammary gland-specific DNMT1 deletion protects mice from mammary tumorigenesis by limiting the CSC pool. Through genome-scale methylation studies, we identify ISL1 as a direct DNMT1 target, hypermethylated and downregulated in mammary tumours and CSCs. DNMT inhibition or ISL1 expression in breast cancer cells limits CSC population. Altogether, our studies uncover an essential role for DNMT1 in MaSC and CSC maintenance and identify DNMT1-ISL1 axis as a potential therapeutic target for breast cancer treatment.

Mammary artery harvesting using the Da Vinci Si robotic system

PubMed Central

Canale, Leonardo Secchin; Bonatti, Johannes

2014-01-01

Internal mammary artery harvesting is an essential part of any coronary artery bypass operation. Totally endoscopic coronary artery bypass graft surgery has become reality in many centers as a safe and effective alternative to conventional surgery in selected patients. Internal mammary artery harvesting is the initial part of the procedure and should be performed equally safely if one wants to achieve excellence in patency rates for the bypass. We here describe the technique for mammary harvesting with the Da Vinci Si robotic system. PMID:24896171

Genetic control of postnatal human brain growth

PubMed Central

van Dyck, Laura I.; Morrow, Eric M.

2017-01-01

Purpose of review Studies investigating postnatal brain growth disorders inform the biology underlying the development of human brain circuitry. This research is becoming increasingly important for the diagnosis and treatment of childhood neurodevelopmental disorders, including autism and related disorders. Here we review recent research on typical and abnormal postnatal brain growth and examine potential biological mechanisms. Recent findings Clinically, brain growth disorders are heralded by diverging head size for a given age and sex, but are more precisely characterized by brain imaging, postmortem analysis, and animal model studies. Recent neuroimaging and molecular biological studies on postnatal brain growth disorders have broadened our view of both typical and pathological postnatal neurodevelopment. Correlating gene and protein function with brain growth trajectories uncovers postnatal biological mechanisms, including neuronal arborization, synaptogenesis and pruning, and gliogenesis and myelination. Recent investigations of childhood neurodevelopmental and neurodegenerative disorders highlight the underlying genetic programming and experience-dependent remodeling of neural circuitry. Summary In order to understand typical and abnormal postnatal brain development, clinicians and researchers should characterize brain growth trajectories in the context of neurogenetic syndromes. Understanding mechanisms and trajectories of postnatal brain growth will aid in differentiating, diagnosing, and potentially treating neurodevelopmental disorders. PMID:27898583

Major epigenetic development distinguishing neuronal and non-neuronal cells occurs postnatally in the murine hypothalamus

USDA-ARS?s Scientific Manuscript database

Prenatal and early postnatal environment can persistently alter one's risk of obesity. Environmental effects on hypothalamic developmental epigenetics constitute a likely mechanism underlying such 'developmental programming' of energy balance regulation. To advance our understanding of these process...

Amphiregulin mediates self-renewal in an immortal mammary epithelial cell line with stem cell characteristics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Booth, Brian W., E-mail: brbooth@clemson.edu; Institute for Biological Interfaces of Engineering, Clemson University, Clemson, SC 29634; Boulanger, Corinne A.

2010-02-01

Amphiregulin (AREG), a ligand for epidermal growth factor receptor, is required for mammary gland ductal morphogenesis and mediates estrogen actions in vivo, emerging as an essential growth factor during mammary gland growth and differentiation. The COMMA-D {beta}-geo (CD{beta}geo) mouse mammary cell line displays characteristics of normal mammary progenitor cells including the ability to regenerate a mammary gland when transplanted into the cleared fat pad of a juvenile mouse, nuclear label retention, and the capacity to form anchorage-independent mammospheres. We demonstrate that AREG is essential for formation of floating mammospheres by CD{beta}geo cells and that the mitogen activated protein kinase signalingmore » pathway is involved in AREG-mediated mammosphere formation. Addition of exogenous AREG promotes mammosphere formation in cells where AREG expression is knocked down by siRNA and mammosphere formation by AREG{sup -/-} mammary epithelial cells. AREG knockdown inhibits mammosphere formation by duct-limited mammary progenitor cells but not lobule-limited mammary progenitor cells. These data demonstrate AREG mediates the function of a subset of mammary progenitor cells in vitro.« less

Amphiregulin mediates self-renewal in an immortal mammary epithelial cell line with stem cell characteristics.

PubMed

Booth, Brian W; Boulanger, Corinne A; Anderson, Lisa H; Jimenez-Rojo, Lucia; Brisken, Cathrin; Smith, Gilbert H

2010-02-01

Amphiregulin (AREG), a ligand for epidermal growth factor receptor, is required for mammary gland ductal morphogenesis and mediates estrogen actions in vivo, emerging as an essential growth factor during mammary gland growth and differentiation. The COMMA-D beta-geo (CDbetageo) mouse mammary cell line displays characteristics of normal mammary progenitor cells including the ability to regenerate a mammary gland when transplanted into the cleared fat pad of a juvenile mouse, nuclear label retention, and the capacity to form anchorage-independent mammospheres. We demonstrate that AREG is essential for formation of floating mammospheres by CDbetageo cells and that the mitogen activated protein kinase signaling pathway is involved in AREG-mediated mammosphere formation. Addition of exogenous AREG promotes mammosphere formation in cells where AREG expression is knocked down by siRNA and mammosphere formation by AREG(-/-) mammary epithelial cells. AREG knockdown inhibits mammosphere formation by duct-limited mammary progenitor cells but not lobule-limited mammary progenitor cells. These data demonstrate AREG mediates the function of a subset of mammary progenitor cells in vitro. Copyright 2009 Elsevier Inc. All rights reserved.

Chemoprevention of Rat Mammary Carcinogenesis by Apiaceae Spices.

PubMed

Aqil, Farrukh; Jeyabalan, Jeyaprakash; Munagala, Radha; Ravoori, Srivani; Vadhanam, Manicka V; Schultz, David J; Gupta, Ramesh C

2017-02-16

Scientific evidence suggests that many herbs and spices have medicinal properties that alleviate symptoms or prevent disease. In this study, we examined the chemopreventive effects of the Apiaceae spices, anise, caraway, and celery seeds against 17β-estrogen (E2)-mediated mammary tumorigenesis in an ACI (August-Copenhagen Irish) rat model. Female ACI rats were given either control diet (AIN 93M) or diet supplemented with 7.5% ( w / w ) of anise, caraway, or celery seed powder. Two weeks later, one half of the animals in each group received subcutaneous silastic implants of E2. Diet intake and body weight were recorded weekly, and animals were euthanized after 3 and 12 weeks. E2-treatment showed significantly (2.1- and 3.4-fold) enhanced growth of pituitary gland at 3 and 12 weeks, respectively. All test spices significantly offset the pituitary growth by 12 weeks, except celery which was effective as early as three weeks. Immunohistochemical analysis for proliferative cell nuclear antigen (PCNA) in mammary tissues showed significant reduction in E2-mediated mammary cell proliferation. Test spices reduced the circulating levels of both E2 and prolactin at three weeks. This protection was more pronounced at 12 weeks, with celery eliciting the highest effect. RT-PCR and western blot analysis were performed to determine the potential molecular targets of the spices. Anise and caraway diets significantly offset estrogen-mediated overexpression of both cyclin D1 and estrogen receptor α (ERα). The effect of anise was modest. Likewise, expression of CYP1B1 and CYP1A1 was inhibited by all test spices. Based on short-term molecular markers, caraway was selected over other spices based on its enhanced effect on estrogen-associated pathway. Therefore, a tumor-end point study in ACI rats was conducted with dietary caraway. Tumor palpation from 12 weeks onwards revealed tumor latency of 29 days in caraway-treated animals compared with first tumor appearance at 92 days in

Chemoprevention of Rat Mammary Carcinogenesis by Apiaceae Spices

PubMed Central

Aqil, Farrukh; Jeyabalan, Jeyaprakash; Munagala, Radha; Ravoori, Srivani; Vadhanam, Manicka V.; Schultz, David J.; Gupta, Ramesh C.

2017-01-01

Scientific evidence suggests that many herbs and spices have medicinal properties that alleviate symptoms or prevent disease. In this study, we examined the chemopreventive effects of the Apiaceae spices, anise, caraway, and celery seeds against 17β-estrogen (E2)-mediated mammary tumorigenesis in an ACI (August-Copenhagen Irish) rat model. Female ACI rats were given either control diet (AIN 93M) or diet supplemented with 7.5% (w/w) of anise, caraway, or celery seed powder. Two weeks later, one half of the animals in each group received subcutaneous silastic implants of E2. Diet intake and body weight were recorded weekly, and animals were euthanized after 3 and 12 weeks. E2-treatment showed significantly (2.1- and 3.4-fold) enhanced growth of pituitary gland at 3 and 12 weeks, respectively. All test spices significantly offset the pituitary growth by 12 weeks, except celery which was effective as early as three weeks. Immunohistochemical analysis for proliferative cell nuclear antigen (PCNA) in mammary tissues showed significant reduction in E2-mediated mammary cell proliferation. Test spices reduced the circulating levels of both E2 and prolactin at three weeks. This protection was more pronounced at 12 weeks, with celery eliciting the highest effect. RT-PCR and western blot analysis were performed to determine the potential molecular targets of the spices. Anise and caraway diets significantly offset estrogen-mediated overexpression of both cyclin D1 and estrogen receptor α (ERα). The effect of anise was modest. Likewise, expression of CYP1B1 and CYP1A1 was inhibited by all test spices. Based on short-term molecular markers, caraway was selected over other spices based on its enhanced effect on estrogen-associated pathway. Therefore, a tumor-end point study in ACI rats was conducted with dietary caraway. Tumor palpation from 12 weeks onwards revealed tumor latency of 29 days in caraway-treated animals compared with first tumor appearance at 92 days in control

Cognitive style, personality and vulnerability to postnatal depression.

PubMed

Jones, Lisa; Scott, Jan; Cooper, Caroline; Forty, Liz; Smith, Katherine Gordon; Sham, Pak; Farmer, Anne; McGuffin, Peter; Craddock, Nick; Jones, Ian

2010-03-01

Only some women with recurrent major depressive disorder experience postnatal episodes. Personality and/or cognitive styles might increase the likelihood of experiencing postnatal depression. To establish whether personality and cognitive style predicts vulnerability to postnatal episodes over and above their known relationship to depression in general. We compared personality and cognitive style in women with recurrent major depressive disorder who had experienced one or more postnatal episodes (postnatal depression (PND) group, n=143) with healthy female controls (control group, n=173). We also examined parous women with recurrent major depressive disorder who experienced no perinatal episodes (non-postnatal depression (NPND) group, n=131). The PND group had higher levels of neuroticism and dysfunctional beliefs, and lower self-esteem than the control group. However, there were no significant differences between the PND and NPND groups. Established personality and cognitive vulnerabilities for depression were reported by women with a history of postnatal depression, but there was no evidence that any of these traits or styles confer a specific risk for the postnatal onset of episodes.

Serum acute phase protein concentrations in female dogs with mammary tumors.

PubMed

Tecles, Fernando; Caldín, Marco; Zanella, Anna; Membiela, Francisco; Tvarijonaviciute, Asta; Subiela, Silvia Martínez; Cerón, José Joaquín

2009-03-01

Acute phase proteins (APPs) are proteins whose concentrations in serum change after any inflammatory stimulus or tissue damage. The aim of the current study was to evaluate 3 positive APPs (C-reactive protein, serum amyloid A, and haptoglobin) and 1 negative APP (albumin) in female dogs with mammary neoplasia. Acute phase proteins were studied in 70 female dogs aged 8-12 years in the following groups: healthy (n = 10); mammary tumors in stages I (n = 19), II (n = 5), III (n = 6), IV (n = 5), and V (n = 7); and with mammary neoplasia plus a concomitant disease (n = 18). In animals with mammary neoplasia, significant increases of positive APPs were only detected in those that had metastasis or a neoplasm with a diameter greater than 5 cm and ulceration. Dogs with mammary neoplasia and a concomitant disease also had high C-reactive protein concentrations. Albumin concentration was decreased in animals with metastasis and with a concomitant disease. The results of the present study indicate that the acute phase response could be stimulated in female dogs with mammary gland tumors because of different factors, such as metastasis, large size of the primary mass, and ulceration or secondary inflammation of the neoplasm.

Postnatal Weight Gain Modifies Severity and Functional Outcome of Oxygen-Induced Proliferative Retinopathy

PubMed Central

Stahl, Andreas; Chen, Jing; Sapieha, Przemyslaw; Seaward, Molly R.; Krah, Nathan M.; Dennison, Roberta J.; Favazza, Tara; Bucher, Felicitas; Löfqvist, Chatarina; Ong, Huy; Hellström, Ann; Chemtob, Sylvain; Akula, James D.; Smith, Lois E.H.

2010-01-01

In clinical studies, postnatal weight gain is strongly associated with retinopathy of prematurity (ROP). However, animal studies are needed to investigate the pathophysiological mechanisms of how postnatal weight gain affects the severity of ROP. In the present study, we identify nutritional supply as one potent parameter that affects the extent of retinopathy in mice with identical birth weights and the same genetic background. Wild-type pups with poor postnatal nutrition and poor weight gain (PWG) exhibit a remarkably prolonged phase of retinopathy compared to medium weight gain or extensive weight gain pups. A high (r2 = 0.83) parabolic association between postnatal weight gain and oxygen-induced retinopathy severity is observed, as is a significantly prolonged phase of proliferative retinopathy in PWG pups (20 days) compared with extensive weight gain pups (6 days). The extended retinopathy is concomitant with prolonged overexpression of retinal vascular endothelial growth factor in PWG pups. Importantly, PWG pups show low serum levels of nonfasting glucose, insulin, and insulin-like growth factor-1 as well as high levels of ghrelin in the early postoxygen-induced retinopathy phase, a combination indicative of poor metabolic supply. These differences translate into visual deficits in adult PWG mice, as demonstrated by impaired bipolar and proximal neuronal function. Together, these results provide evidence for a pathophysiological correlation between poor postnatal nutritional supply, slow weight gain, prolonged retinal vascular endothelial growth factor overexpression, protracted retinopathy, and reduced final visual outcome. PMID:21056995

Postnatal weight gain modifies severity and functional outcome of oxygen-induced proliferative retinopathy.

PubMed

Stahl, Andreas; Chen, Jing; Sapieha, Przemyslaw; Seaward, Molly R; Krah, Nathan M; Dennison, Roberta J; Favazza, Tara; Bucher, Felicitas; Löfqvist, Chatarina; Ong, Huy; Hellström, Ann; Chemtob, Sylvain; Akula, James D; Smith, Lois E H

2010-12-01

In clinical studies, postnatal weight gain is strongly associated with retinopathy of prematurity (ROP). However, animal studies are needed to investigate the pathophysiological mechanisms of how postnatal weight gain affects the severity of ROP. In the present study, we identify nutritional supply as one potent parameter that affects the extent of retinopathy in mice with identical birth weights and the same genetic background. Wild-type pups with poor postnatal nutrition and poor weight gain (PWG) exhibit a remarkably prolonged phase of retinopathy compared to medium weight gain or extensive weight gain pups. A high (r(2) = 0.83) parabolic association between postnatal weight gain and oxygen-induced retinopathy severity is observed, as is a significantly prolonged phase of proliferative retinopathy in PWG pups (20 days) compared with extensive weight gain pups (6 days). The extended retinopathy is concomitant with prolonged overexpression of retinal vascular endothelial growth factor in PWG pups. Importantly, PWG pups show low serum levels of nonfasting glucose, insulin, and insulin-like growth factor-1 as well as high levels of ghrelin in the early postoxygen-induced retinopathy phase, a combination indicative of poor metabolic supply. These differences translate into visual deficits in adult PWG mice, as demonstrated by impaired bipolar and proximal neuronal function. Together, these results provide evidence for a pathophysiological correlation between poor postnatal nutritional supply, slow weight gain, prolonged retinal vascular endothelial growth factor overexpression, protracted retinopathy, and reduced final visual outcome.

Dietary zinc supplementation throughout pregnancy protects against fetal dysmorphology and improves postnatal survival after prenatal ethanol exposure in mice.

PubMed

Summers, Brooke L; Rofe, Allan M; Coyle, Peter

2009-04-01

We have previously demonstrated that ethanol teratogenicity is associated with metallothionein-induced fetal zinc (Zn) deficiency, and that maternal subcutaneous Zn treatment given with ethanol in early pregnancy prevents fetal abnormalities and spatial memory impairments in mice. Here we investigated whether dietary Zn supplementation throughout pregnancy can also prevent ethanol-related dysmorphology. Pregnant mice were injected with saline or 25% ethanol (0.015 ml/g intraperitoneally at 0 and 4 hours) on gestational day (GD) 8 and fed either a control (35 mg Zn/kg) or a Zn-supplemented diet (200 mg Zn/kg) from GD 0 to 18. Fetuses from the saline, saline + Zn, ethanol and ethanol + Zn groups were assessed for external birth abnormalities on GD 18. In a separate cohort of mice, postnatal growth and survival of offspring from these treatment groups were examined from birth until postnatal day 60. Fetuses from dams treated with ethanol alone in early pregnancy had a significantly greater incidence of physical abnormalities (26%) compared to those from the saline (10%), saline + Zn (9%), or ethanol + Zn (12%) groups. The incidence of abnormalities in ethanol + Zn-supplemented fetuses was not different from saline-treated fetuses. While ethanol exposure did not affect the number of fetal resorptions or pre- or postnatal weight, there were more stillbirths with ethanol alone, and cumulative postnatal mortality was significantly higher in offspring exposed to ethanol alone (35% deaths) compared to all other treatment groups (13.5 to 20.5% deaths). Mice supplemented with Zn throughout pregnancy had higher plasma Zn concentrations than those in un-supplemented groups. These findings demonstrate that dietary Zn supplementation throughout pregnancy ameliorates dysmorphology and postnatal mortality caused by ethanol exposure in early pregnancy.

Th-POK regulates mammary gland lactation through mTOR-SREBP pathway.

PubMed

Zhang, Rui; Ma, Huimin; Gao, Yuan; Wu, Yanjun; Qiao, Yuemei; Geng, Ajun; Cai, Cheguo; Han, Yingying; Zeng, Yi Arial; Liu, Xiaolong; Ge, Gaoxiang

2018-02-01

The Th-inducing POK (Th-POK, also known as ZBTB7B or cKrox) transcription factor is a key regulator of lineage commitment of immature T cell precursors. It is yet unclear the physiological functions of Th-POK besides helper T cell differentiation. Here we show that Th-POK is restrictedly expressed in the luminal epithelial cells in the mammary glands that is upregulated at late pregnancy and lactation. Lineage restrictedly expressed Th-POK exerts distinct biological functions in the mammary epithelial cells and T cells in a tissue-specific manner. Th-POK is not required for mammary epithelial cell fate determination. Mammary gland morphogenesis in puberty and alveologenesis in pregnancy are phenotypically normal in the Th-POK-deficient mice. However, Th-POK-deficient mice are defective in triggering the onset of lactation upon parturition with large cellular lipid droplets retained within alveolar epithelial cells. As a result, Th-POK knockout mice are unable to efficiently secret milk lipid and to nurse the offspring. Such defect is mainly attributed to the malfunctioned mammary epithelial cells, but not the tissue microenvironment in the Th-POK deficient mice. Th-POK directly regulates expression of insulin receptor substrate-1 (IRS-1) and insulin-induced Akt-mTOR-SREBP signaling. Th-POK deficiency compromises IRS-1 expression and Akt-mTOR-SREBP signaling in the lactating mammary glands. Conversely, insulin induces Th-POK expression. Thus, Th-POK functions as an important feed-forward regulator of insulin signaling in mammary gland lactation.

Th-POK regulates mammary gland lactation through mTOR-SREBP pathway

PubMed Central

Wu, Yanjun; Qiao, Yuemei; Geng, Ajun; Cai, Cheguo; Han, Yingying; Zeng, Yi Arial

2018-01-01

The Th-inducing POK (Th-POK, also known as ZBTB7B or cKrox) transcription factor is a key regulator of lineage commitment of immature T cell precursors. It is yet unclear the physiological functions of Th-POK besides helper T cell differentiation. Here we show that Th-POK is restrictedly expressed in the luminal epithelial cells in the mammary glands that is upregulated at late pregnancy and lactation. Lineage restrictedly expressed Th-POK exerts distinct biological functions in the mammary epithelial cells and T cells in a tissue-specific manner. Th-POK is not required for mammary epithelial cell fate determination. Mammary gland morphogenesis in puberty and alveologenesis in pregnancy are phenotypically normal in the Th-POK-deficient mice. However, Th-POK-deficient mice are defective in triggering the onset of lactation upon parturition with large cellular lipid droplets retained within alveolar epithelial cells. As a result, Th-POK knockout mice are unable to efficiently secret milk lipid and to nurse the offspring. Such defect is mainly attributed to the malfunctioned mammary epithelial cells, but not the tissue microenvironment in the Th-POK deficient mice. Th-POK directly regulates expression of insulin receptor substrate-1 (IRS-1) and insulin-induced Akt-mTOR-SREBP signaling. Th-POK deficiency compromises IRS-1 expression and Akt-mTOR-SREBP signaling in the lactating mammary glands. Conversely, insulin induces Th-POK expression. Thus, Th-POK functions as an important feed-forward regulator of insulin signaling in mammary gland lactation. PMID:29420538

Pre-natal and post-natal growth trajectories and childhood cognitive ability and mental health.

PubMed

Yang, Seungmi; Tilling, Kate; Martin, Richard; Davies, Neil; Ben-Shlomo, Yoav; Kramer, Michael S

2011-10-01

Most studies of the associations between pre-natal or post-natal growth and cognitive ability have been based on children with pathologically slow growth measured between two time points only, rather than children with normal growth trajectories estimated from multiple measures of growth. We investigated the associations of pre-natal and post-natal trajectories in both weight and length/height through the first 5 years of life with cognitive ability and mental health at 6.5 years of age among healthy children. Our study is based on 11 899 children who were born healthy at ≥37 completed weeks with birth weight ≥2500 g and had up to 13 measures of weight and length/height from birth to age 5 years and cognitive ability and behaviour measured at 6.5 years. Using a linear spline random-effects model with 2 knots at 3 and 12 months, we estimated growth trajectories for each child from birth to age 5 years in weight and length/height in four periods: gestational age-specific birth weight and length (pre-natal 'growth'), early infancy (0-3 months), late infancy (3-12 months) and early childhood (1-5 years). We used generalized estimating equations to estimate mean differences in IQ and mental health according to pre-natal and post-natal growth trajectory. IQ was measured using the Wechsler Abbreviated Scales of Intelligence, and mental health was assessed using the Strengths and Difficulties Questionnaire. A 1 standard deviation (SD) in birth weight was positively associated with cognitive ability (0.82 IQ points, 95% CI: 0.54-1.10) after adjusting for confounders. For post-natal weight gain trajectories, a 1 SD faster weight gain was associated with an increase of 0.77 (95% CI: 0.42-1.11) IQ points for early infancy, 0.30 (95% CI: 0.02-0.58) points for late infancy, and 0.40 (95% CI: 0.04-0.76) for early childhood after adjusting for confounders and for earlier growth. For length/height trajectories, the magnitudes of increase in cognitive ability were similar

Immortalized bovine mammary epithelial cells express stem cell markers and differentiate in vitro.

PubMed

Hu, Han; Zheng, Nan; Gao, Haina; Dai, Wenting; Zhang, Yangdong; Li, Songli; Wang, Jiaqi

2016-08-01

The bovine mammary epithelial cell is a secretory cell, and its cell number and secretory activity determine milk production. In this study, we immortalized a bovine mammary epithelial cell line by SV40 large T antigen gene using a retrovirus based on Chinese Holstein primary mammary epithelial cells (CMEC) cultured in vitro. An immortalized bovine mammary epithelial cell line surpassed the 50-passage mark and was designated the CMEC-H. The immortalized mammary epithelial cells grew in close contact with each other and exhibited the typical cobblestone morphology characteristic with obvious boundaries. The telomerase expression of CMEC-H has consistently demonstrated the presence of telomerase activity as an immortalized cell line, but the cell line never induced tumor formation in nude mice. CMEC-H expressed epithelial (cytokeratins CK7, CK8, CK18, and CK19), mesenchymal (vimentin), and stem/progenitor (CD44 and p63) cell markers. The induced expression of milk proteins, αS1 -casein, β-casein, κ-casein, and butyrophilin, indicated that CMEC-H maintained the synthesis function of the mammary epithelial cells. The established immortalized bovine mammary epithelial cell line CMEC-H is capable of self-renewal and differentiation and can serve as a valuable reagent for studying the physiological mechanism of the mammary gland. © 2016 International Federation for Cell Biology.

Prenatal and Postnatal Cell Phone Exposures and Headaches in Children.

PubMed

Sudan, Madhuri; Kheifets, Leeka; Arah, Onyebuchi; Olsen, Jorn; Zeltzer, Lonnie

2012-12-05

Children today are exposed to cell phones early in life, and may be at the greatest risk if exposure is harmful to health. We investigated associations between cell phone exposures and headaches in children. The Danish National Birth Cohort enrolled pregnant women between 1996 and 2002. When their children reached age seven years, mothers completed a questionnaire regarding the child's health, behaviors, and exposures. We used multivariable adjusted models to relate prenatal only, postnatal only, or both prenatal and postnatal cell phone exposure to whether the child had migraines and headache-related symptoms. Our analyses included data from 52,680 children. Children with cell phone exposure had higher odds of migraines and headache-related symptoms than children with no exposure. The odds ratio for migraines was 1.30 (95% confidence interval: 1.01-1.68) and for headache-related symptoms was 1.32 (95% confidence interval: 1.23-1.40) for children with both prenatal and postnatal exposure. In this study, cell phone exposures were associated with headaches in children, but the associations may not be causal given the potential for uncontrolled confounding and misclassification in observational studies such as this. However, given the widespread use of cell phones, if a causal effect exists it would have great public health impact.

Innovative look at dairy heifer rearing: Effect of prenatal and post-natal environment on later performance.

PubMed

Van Eetvelde, M; Opsomer, G

2017-08-01

As heifer rearing is a costly investment, dairy farmers have been stimulated to maximize early growth of their calves, mainly by enhanced liquid feeding. However, the long-term effects of this "accelerated growth" are largely unknown. Studies recently performed at Ghent University indicate that in dairy cattle, certain maternal factors (such as young age and high milk yield) and environmental factors (such as high ambient temperatures) create a suboptimal environment for the developing foetus, altering the phenotype of the newborn calf. According to the "thrifty phenotype hypothesis," these metabolic alterations prepare the newborn for similar ("matching") conditions after birth, enhancing its survival during periods of limited feeding. Yet, when an abundance of nutrients is available in post-natal life (e.g., during periods of enhanced feeding), the "mismatch" between pre- and post-natal environment results in an early catch-up growth, with potential negative consequences. The aim of the article was to discuss this mismatch between pre- and post-natal environment in dairy calves. Previous studies, especially in human medicine, have shown catch-up growth to be associated with obesity, fertility problems, metabolic diseases and a reduced lifespan. Hence, we hypothesize that, by applying programs of accelerated growth, our current management system accentuates the mismatch between the pre- and post-natal environment in dairy calves. We can conclude that, although more research is necessary, the current findings point towards a more individual approach when rearing dairy heifers. © 2017 Blackwell Verlag GmbH.

Antenatal and early infant predictors of postnatal growth in rural Vietnam: a prospective cohort study.

PubMed

Hanieh, Sarah; Ha, Tran T; De Livera, Alysha M; Simpson, Julie A; Thuy, Tran T; Khuong, Nguyen C; Thoang, Dang D; Tran, Thach D; Tuan, Tran; Fisher, Jane; Biggs, Beverley-Ann

2015-02-01

To determine which antenatal and early-life factors were associated with infant postnatal growth in a resource-poor setting in Vietnam. Prospective longitudinal study following infants (n=1046) born to women who had previously participated in a cluster randomised trial of micronutrient supplementation (ANZCTR:12610000944033), Ha Nam province, Vietnam. Antenatal and early infant factors were assessed for association with the primary outcome of infant length-for-age z scores at 6 months of age using multivariable linear regression and structural equation modelling. Mean length-for-age z score was -0.58 (SD 0.94) and stunting prevalence was 6.4%. Using structural equation modelling, we highlighted the role of infant birth weight as a predictor of infant growth in the first 6 months of life and demonstrated that maternal body mass index (estimated coefficient of 45.6 g/kg/m(2); 95% CI 34.2 to 57.1), weight gain during pregnancy (21.4 g/kg; 95% CI 12.6 to 30.1) and maternal ferritin concentration at 32 weeks' gestation (-41.5 g per twofold increase in ferritin; 95% CI -78 to -5.0) were indirectly associated with infant length-for-age z scores at 6 months of age via birth weight. A direct association between 25-(OH) vitamin D concentration in late pregnancy and infant length-for-age z scores (estimated coefficient of -0.06 per 20 nmol/L; 95% CI -0.11 to -0.01) was observed. Maternal nutritional status is an important predictor of early infant growth. Elevated antenatal ferritin levels were associated with suboptimal infant growth in this setting, suggesting caution with iron supplementation in populations with low rates of iron deficiency. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The RhoGEF Net1 Is Required for Normal Mammary Gland Development

PubMed Central

Zuo, Yan; Berdeaux, Rebecca

2014-01-01

Neuroepithelial transforming gene 1 (Net1) is a RhoA subfamily-specific guanine nucleotide exchange factor that is overexpressed in human breast cancer and is required for breast cancer cell migration and invasion. However, the role of Net1 in normal mammary gland development or function has never been assessed. To understand the role of Net1 in the mammary gland, we have created a conditional Net1 knockout mouse model. Whole-body deletion of Net1 results in delayed mammary gland development during puberty characterized by slowed of ductal extension and reduced ductal branching. Epithelial cells within the developing ducts show reduced proliferation that is accompanied by diminished estrogen receptor-α expression and activity. Net1-deficient mammary glands also exhibit reduced phosphorylation of regulatory subunits of myosin light chain and myosin light-chain phosphatase, indicating that RhoA-dependent actomyosin contraction is compromised. Net1 deficiency also leads to disorganization of myoepithelial and ductal epithelial cells and increased periductal collagen deposition. Mammary epithelial cell transplantation experiments indicate that reduced ductal branching and disorganization are cell autonomous. These data identify for the first time a role for NET1 in vivo and indicate that NET1 expression is essential for the proliferation and differentiation of mammary epithelial cells in the developing mammary gland. PMID:25321414

Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells

NASA Technical Reports Server (NTRS)

Goepfert, T. M.; McCarthy, M.; Kittrell, F. S.; Stephens, C.; Ullrich, R. L.; Brinkley, B. R.; Medina, D.

2000-01-01

Mammary epithelial cells from p53 null mice have been shown recently to exhibit an increased risk for tumor development. Hormonal stimulation markedly increased tumor development in p53 null mammary cells. Here we demonstrate that mammary tumors arising in p53 null mammary cells are highly aneuploid, with greater than 70% of the tumor cells containing altered chromosome number and a mean chromosome number of 56. Normal mammary cells of p53 null genotype and aged less than 14 wk do not exhibit aneuploidy in primary cell culture. Significantly, the hormone progesterone, but not estrogen, increases the incidence of aneuploidy in morphologically normal p53 null mammary epithelial cells. Such cells exhibited 40% aneuploidy and a mean chromosome number of 54. The increase in aneuploidy measured in p53 null tumor cells or hormonally stimulated normal p53 null cells was not accompanied by centrosome amplification. These results suggest that normal levels of progesterone can facilitate chromosomal instability in the absence of the tumor suppressor gene, p53. The results support the emerging hypothesis based both on human epidemiological and animal model studies that progesterone markedly enhances mammary tumorigenesis.

Mammary gigantism and D-penicillamine.

PubMed

Finer, N; Emery, P; Hicks, B H

1984-09-01

Mammary gigantism is a rare complication of D-penicillamine treatment. We report a further case with pathological and endocrine details together with a review of the seven cases previously reported and possible mechanisms.

Influence of socio-economic factors on emotional changes during the postnatal period.

PubMed

Wszołek, Katarzyna; Żak, Ewa; Żurawska, Joanna; Olszewska, Jolanta; Pięta, Beata; Bojar, Iwona

2018-03-14

The aim of the study was to identify socio-economic factors that may influence the emotional changes which occur among new mothers in the first days postpartum. A group of 541 women completed a questionnaire consisting of 30 multiple-choice questions, Edinburgh Postnatal Depression Scale (EPDS), and Hospital Anxiety and Depression Scale (HADS). Statistical calculations were performed with the use of Statistica v.10 and Cytel Studio v. 9.0.0. The findings revealed the presence of factors which might increase the risk of mood disorders during the postpartum period. Women who demonstrate warning symptoms should be screened for postnatal emotional changes and mood swings during their hospitalization after delivery. EPDS seems to be a suitable tool for early detection of emotional disturbances.

Investigating the Role of FIP200 in Mammary Carcinogenesis Using a Transgenic Mouse Model

DTIC Science & Technology

2006-04-01

I analyzed virgin and lactating female mice in which FAK is specifically deleted in the mammary epithelium. No morphological abnormalities were found...in the mammary gland of virgin mice however, lactating mice have severe lobulo-alveolar hypoplasia in the mammary gland. 15. SUBJECT TERMS... virgin and lactating female mice in which FAK is specifically deleted in the mammary epithelium. No morphological abnormalities were found in the

Pre- and Postnatal Influences on Preschool Mental Health: A Large-Scale Cohort Study

ERIC Educational Resources Information Center

Robinson, Monique; Oddy, Wendy H.; Li, Jianghong; Kendall, Garth E.; de Klerk, Nicholas H.; Silburn, Sven R.; Zubrick, Stephen R.; Newnham, John P.; Stanley, Fiona J.; Mattes, Eugen

2008-01-01

Background: Methodological challenges such as confounding have made the study of the early determinants of mental health morbidity problematic. This study aims to address these challenges in investigating antenatal, perinatal and postnatal risk factors for the development of mental health problems in pre-school children in a cohort of Western…

Brca1 regulates in vitro differentiation of mammary epithelial cells.

PubMed

Kubista, Marion; Rosner, Margit; Kubista, Ernst; Bernaschek, Gerhard; Hengstschläger, Markus

2002-07-18

Murine Brca1 is widely expressed during development in different tissues. Why alterations of BRCA1 lead specifically to breast and ovarian cancer is currently not clarified. Here we show that Brca1 protein expression is upregulated during mammary epithelial differentiation of HC11 cells, during differentiation of C2C12 myoblasts into myotubes and during neuronal differentiation of N1E-115 cells. Ectopic overexpression of BRCA1 and downregulation of endogenous Brca1 expression specifically affect the regulation of mammary epithelial cell differentiation. Accelerated mammary epithelial cell differentiation upon high ectopic BRCA1 expression is not a consequence of the anti-proliferative capacity of this tumor suppressor and independent of functional p53. Overexpression of the BRCA1 variant lacking the large central exon 11 has no effects on mammary epithelial cell differentiation. These data provide new insights into the cellular role of Brca1.

Histomorphometry and expression of CDC-47 and caspase-3 in mammary glands of pregnant female rats with artificial hyperthyroidism.

PubMed

Leite, Eveline Dias; de Freitas, Edmilson Santos; de Almeida Souza, Cintia; de Melo Ocarino, Natalia; Cassali, Geovanni Dantas; Serakides, Rogéria

2008-01-01

The purpose of this study was to evaluate the effect of hyperthyroidism on mammary gland development and expression of two protein markers, CDC-47 for proliferation and caspase-3 for apoptosis in pregnant female rats. Thirty-six adult female Wistar rats were used in two groups: hyperthyroid and control. Rats were mated 60 days after the onset of thyroxine administration. Six animals/group were sacrificed on gestation days 7, 14, and 19. Artificial hyperthyroidism was induced by daily administration of thyroxine in the drinking water until the end of gestation. At the end of each period, rats were sacrificed, and their inguinal mammary glands were collected and processed for morphometric analysis. The percentages of epithelium, stroma, adipose tissue, and lacteal secretion were determined. Immunohistochemical analysis was also carried out using anti-CDC-47 and anti-caspase-3 antibodies to study proliferation and apoptosis, respectively. On the 19th day of gestation, thyroxine treatment significantly increased the percentage of mammary epithelium. Hyperthyroidism, however, did not change CDC-47 expression. The hyperthyroid group presented early lactogenesis and significantly larger lacteal secretion on the 19th day of gestation. There was no significant difference in caspase-3 expression between groups in any period. We may conclude that hyperthyroidism accelerates mammary gland development and increases lacteal secretion during gestation without increasing the proliferation rate and the expression of caspase-3.

The mammary gland in domestic ruminants: a systems biology perspective.

PubMed

Ferreira, Ana M; Bislev, Stine L; Bendixen, Emøke; Almeida, André M

2013-12-06

Milk and dairy products are central elements in the human diet. It is estimated that 108kg of milk per year are consumed per person worldwide. Therefore, dairy production represents a relevant fraction of the economies of many countries, being cattle, sheep, goat, water buffalo, and other ruminants the main species used worldwide. An adequate management of dairy farming cannot be achieved without the knowledge on the biological mechanisms behind lactation in ruminants. Thus, understanding the morphology, development and regulation of the mammary gland in health, disease and production is crucial. Presently, innovative and high-throughput technologies such as genomics, transcriptomics, proteomics and metabolomics allow a much broader and detailed knowledge on such issues. Additionally, the application of a systems biology approach to animal science is vastly growing, as new advances in one field of specialization or animal species lead to new lines of research in other areas or/and are expanded to other species. This article addresses how modern research approaches may help us understand long-known issues in mammary development, lactation biology and dairy production. Dairy production depends upon the knowledge of the morphology and regulation of the mammary gland and lactation. High-throughput technologies allow a much broader and detailed knowledge on the biology of the mammary gland. This paper reviews the major contributions that genomics, transcriptomics, metabolomics and proteomics approaches have provided to understand the regulation of the mammary gland in health, disease and production. In the context of mammary gland "omics"-based research, the integration of results using a Systems Biology Approach is of key importance. © 2013.

Phenotypic conversion of human mammary carcinoma cells by autocrine human growth hormone

PubMed Central

Mukhina, Svetlana; Mertani, Hichem C.; Guo, Ke; Lee, Kok-Onn; Gluckman, Peter D.; Lobie, Peter E.

2004-01-01

We report here that autocrine production of human growth hormone (hGH) results in a phenotypic conversion of mammary carcinoma cells such that they exhibit the morphological and molecular characteristics of a mesenchymal cell, including expression of fibronectin and vimentin. Autocrine production of hGH resulted in reduced plakoglobin expression and relocalization of E-cadherin to the cytoplasm, leading to dissolution of cell-cell contacts and decreased cell height. These phenotypic changes were accompanied by an increase in cell motility, elevated activity of specific matrix metalloproteinases, and an acquired ability to invade a reconstituted basement membrane. Forced expression of plakoglobin significantly decreased mammary carcinoma cell migration and invasion stimulated by autocrine hGH. In vivo, autocrine hGH stimulated local invasion of mammary carcinoma cells concomitant with a prominent stromal reaction in comparison with well delineated and capsulated growth of mammary carcinoma cells lacking autocrine production of hGH. Thus, autocrine production of hGH by mammary carcinoma cells is sufficient for generation of an invasive phenotype. Therapeutic targeting of autocrine hGH may provide a mechanistic approach to prevent metastatic extension of human mammary carcinoma. PMID:15353581

The Role of DN-GSK3beta in Mammary Tumorigenesis

DTIC Science & Technology

2006-07-01

factors and dramatically increases their transcriptional activity. Genes up- regulated by TCF/LEF include embryologic genes, such as siamois and engrailed...and increased apoptosis occurs in the mammary epithelia (33). Overexpression of the regulator CK2a also promotes mammary tumorigenesis (34). In this

Familial intra-areolar polythelia with mammary hypoplasia.

PubMed

Rintala, A; Norio, R

1982-01-01

Dysplastic divided nipples (intra-areolar polythelia) have been found bilaterally in a mother, her two daughters and one son. Two of the patients had mammary hypoplasia, one had unilateral hypoplasia of the pectoral muscle and duplication of the renal pelvis and ureter. The mammary findings are consistent with autosomal dominant inheritance. Whether they represent a new mammo-renal syndrome is uncertain. Reconstructive surgery was performed on two patients. Due to the deformity the mother was unable to nurse her children; following reconstructive surgery the daughter was able to feed her baby normally.

Influence of caffeine and/or coffee consumption on the initiation and promotion phases of 7,12-dimethylbenz(a)anthracene-induced rat mammary gland tumorigenesis.

PubMed

Welsch, C W; DeHoog, J V; O'Connor, D H

1988-04-15

The effect of caffeine and/or coffee consumption (via the drinking water) during the initiation phase and promotion phase of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary gland tumorigenesis in female Sprague-Dawley rats fed a commercial laboratory animal chow was examined. In the initiation studies, DMBA was administered once at 53-55 days of age; caffeine (100-860 mg/liter of drinking water) and/or coffee (moderate or high dose, sole source of drinking water) treatments were for 32 consecutive days, commencing 29 days prior to DMBA treatment and terminating 3 days after DMBA treatment. In the promotion studies, DMBA was administered once at 54-55 days of age; caffeine and/or coffee treatments were daily from 57-58 days of age to termination of experiments (12-21 weeks after carcinogen treatment). In the initiation studies, either moderate (100-400 mg) or high (860 mg) dose levels of caffeine or moderate to high dose levels of caffeinated coffee significantly (P less than 0.05) reduced mammary carcinoma multiplicity (number of tumors/rat). Consumption of high or moderate dose levels of decaffeinated coffee did not significantly alter mammary carcinoma multiplicity. The addition of caffeine to the moderate dose level of decaffeinated coffee resulted in a significant (P less than 0.05) reduction in mammary carcinoma multiplicity. In the promotion studies, prolonged consumption of moderated dose levels of caffeine or moderate or high dose levels of caffeinated coffee or decaffeinated coffee did not significantly effect mammary carcinoma multiplicity. In the early stages of promotion, however, a significant (p less than 0.05) stimulatory effect of caffeine on mammary carcinoma multiplicity was observed; an effect that was temperate and transitory. In both the initiation and promotion studies caffeine and/or coffee consumption did not significantly affect the incidence of mammary carcinomas (percentage of rats bearing mammary carcinomas) or the mean latency

Over-expression of mammaglobin-B in canine mammary tumors.

PubMed

Pandey, Mamta; Sunil Kumar, B V; Gupta, Kuldip; Sethi, Ram Saran; Kumar, Ashwani; Verma, Ramneek

2018-06-15

Mammaglobin, a member of secretoglobin family has been recognized as a breast cancer associated protein. Though the exact function of the protein is not fully known, its expression has been reported to be upregulated in human breast cancer.We focused on studying the expression of mammaglobin-B gene and protein in canine mammary tumor (CMT) tissue. Expression of mammaglobin-B mRNA and protein were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC), respectively. High levels of mammaglobin-B mRNA expression (6.663 ± 0.841times) was observed in CMT as compared to age and breed matched healthy controls. Further, expression of mammaglobin-B protein was detected in paraffin-embedded mammary tumor tissues from the same subjects by IHC. Mammaglobin-B protein was overexpressed only in 6.67% of healthy mammary glands while, a high level of its expression was scored in 76.7% of the CMT subjects. Moreover, no significant differences in terms of IHC score and qRT-PCR score with respect to CMT histotypes or tumor grades were observed, indicating that mammaglobin-B over-expression occurred irrespective of CMT types or grades. Overall, significantly increased expression of mammaglobin-B protein was found in CMTs with respect to healthy mammary glands, which positively correlates to its transcript. These findings suggest that overexpression of mammaglobin-B is associated with tumors of canine mammary glands.

Culture models of human mammary epithelial cell transformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stampfer, Martha R.; Yaswen, Paul

2000-11-10

Human pre-malignant breast diseases, particularly ductal carcinoma in situ (DCIS)3 already display several of the aberrant phenotypes found in primary breast cancers, including chromosomal abnormalities, telomerase activity, inactivation of the p53 gene and overexpression of some oncogenes. Efforts to model early breast carcinogenesis in human cell cultures have largely involved studies in vitro transformation of normal finite lifespan human mammary epithelial cells (HMEC) to immortality and malignancy. We present a model of HMEC immortal transformation consistent with the know in vivo data. This model includes a recently described, presumably epigenetic process, termed conversion, which occurs in cells that have overcomemore » stringent replicative senescence and are thus able to maintain proliferation with critically short telomeres. The conversion process involves reactivation of telomerase activity, and acquisition of good uniform growth in the absence and presence of TFGB. We propose th at overcoming the proliferative constraints set by senescence, and undergoing conversion, represent key rate-limiting steps in human breast carcinogenesis, and occur during early stage breast cancer progression.« less

Maternal Forced Swimming Reduces Cell Proliferation in the Postnatal Dentate Gyrus of Mouse Offspring

PubMed Central

Wasinski, Frederick; Estrela, Gabriel R.; Arakaki, Aline M.; Bader, Michael; Alenina, Natalia; Klempin, Friederike; Araújo, Ronaldo C.

2016-01-01

Physical exercise positively affects the metabolism and induces proliferation of precursor cells in the adult brain. Maternal exercise likewise provokes adaptations early in the offspring. Using a high-intensity swimming protocol that comprises forced swim training before and during pregnancy, we determined the effect of maternal swimming on the mouse offspring's neurogenesis. Our data demonstrate decreased proliferation in sublayers of the postnatal dentate gyrus in offspring of swimming mother at postnatal day (P) 8 accompanied with decreased survival of newly generated cells 4 weeks later. The reduction in cell numbers was predominantly seen in the hilus and molecular layer. At P35, the reduced amount of cells was also reflected by a decrease in the population of newly generated immature and mature neurons of the granule cell layer. Our data suggest that forced maternal swimming at high-intensity has a negative effect on the neurogenic niche development in postnatal offspring. PMID:27621701

Is Bilateral Internal Mammary Arterial Grafting Beneficial for Patients Aged 75 Years or Older?

PubMed

Itoh, Satoshi; Kimura, Naoyuki; Adachi, Hideo; Yamaguchi, Atsushi

2016-07-25

Although bilateral internal mammary artery (BIMA) grafting is performed with increasing regularity in elderly patients, whether it is truly beneficial, and therefore indicated, in these patients remains uncertain. We retrospectively investigated early and late outcomes of BIMA grafting in patients aged ≥75 years. We identified 460 patients aged ≥75 years from among 2,618 patients who underwent either single internal mammary artery (SIMA) grafting (n=293) or BIMA grafting (n=107). Early outcomes did not differ between the SIMA and BIMA patients (30-day mortality: 1.7% vs. 0%, P=0.39; sternal wound infection: 1.0% vs. 4.7%; P=0.057). Late outcomes, 10-year survival in particular, were improved in the BIMA group (36.6% vs. 48.1%, P=0.033). In the analysis of the results in propensity score-matched groups (196 patients in the SIMA group, 98 patients in the BIMA group), improved 10-year survival was documented in the BIMA group (34.8% vs. 47.6%, P=0.030). Cox proportional regression analysis showed SIMA usage (non-use of BIMA) to be a predictor for late mortality (hazard ratio: 0.65, 95% confidence interval: 0.43-0.98, P=0.042). We further compared outcomes between the total non-elderly patients (n=2,158) and total elderly patients (n=460). BIMA usage was similar, as was 30-day mortality (1.0% vs. 1.3%, respectively). A survival advantage, with no increase in early mortality, can be expected from BIMA grafting in patients aged ≥75 years. (Circ J 2016; 80: 1756-1763).

Mammary fibroadenomatous hyperplasia in a young cat attributed to treatment with megestrol acetate.

PubMed

MacDougall, Lori D

2003-03-01

A male, neutered cat was presented for lethargy, reluctance to walk, and mammary enlargement after recent treatment with megestrol acetate. Mammary fibroadenomatous hyperplasia was diagnosed on the basis of history, clinical signs, and histopathological findings. Pathogenesis, clinical signs, and treatment options for mammary fibroadenomatous hyperplasia attributed to megestrol acetate treatment are discussed.

Anterograde Tracing Method using DiI to Label Vagal Innervation of the Embryonic and Early Postnatal Mouse Gastrointestinal Tract

PubMed Central

Murphy, Michelle C.; Fox, Edward A.

2007-01-01

The mouse is an extremely valuable model for studying vagal development in relation to strain differences, genetic variation, gene manipulations, or pharmacological manipulations. Therefore, a method using 1, 1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) was developed for labeling vagal innervation of the gastrointestinal (GI) tract in embryonic and postnatal mice. DiI labeling was adapted and optimized for this purpose by varying several facets of the method. For example, insertion and crushing of DiI crystals into the nerve led to faster DiI diffusion along vagal axons and diffusion over longer distances as compared with piercing the nerve with a micropipette tip coated with dried DiI oil. Moreover, inclusion of EDTA in the fixative reduced leakage of DiI out of nerve fibers that occurred with long incubations. Also, mounting labeled tissue in PBS was superior to glycerol with n-propyl gallate, which resulted in reduced clarity of DiI labeling that may have been due to DiI leaking out of fibers. Optical sectioning of flattened wholemounts permitted examination of individual tissue layers of the GI tract wall. This procedure aided identification of nerve ending types because in most instances each type innervates a different tissue layer. Between embryonic day 12.5 and postnatal day 8, growth of axons into the GI tract, formation and patterning of fiber bundles in the myenteric plexus and early formation of putative afferent and efferent nerve terminals were observed. Thus, the DiI tracing method developed here has opened up a window for investigation during an important phase of vagal development. PMID:17418900

Notch3 marks clonogenic mammary luminal progenitor cells in vivo.

PubMed

Lafkas, Daniel; Rodilla, Veronica; Huyghe, Mathilde; Mourao, Larissa; Kiaris, Hippokratis; Fre, Silvia

2013-10-14

The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive "triple negative" human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2(SAT) transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells.

Notch3 marks clonogenic mammary luminal progenitor cells in vivo

PubMed Central

Lafkas, Daniel; Rodilla, Veronica; Huyghe, Mathilde; Mourao, Larissa; Kiaris, Hippokratis

2013-01-01

The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive “triple negative” human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2SAT transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells. PMID:24100291

Antenatal iron/folic acid supplements, but not postnatal care, prevents neonatal deaths in Indonesia: analysis of Indonesia Demographic and Health Surveys 2002/2003–2007 (a retrospective cohort study)

PubMed Central

Titaley, Christiana Rialine; Dibley, Michael John

2012-01-01

Objective This study aimed to assess the contribution of postnatal services to the risk of neonatal mortality, and the relative contributions of antenatal iron/folic acid supplements and postnatal care in preventing neonatal mortality in Indonesia. Design Retrospective cohort study. Setting and participants Data used in this study were the 2002–2007 Indonesia Demographic and Health Surveys, nationally representative surveys. The pooled data provided survival information of 26 591 most recent live-born infants within the 5-years prior to each interview. Primary outcomes Primary outcomes were early neonatal mortality, that is, deaths in the first week, and all neonatal mortality, that is, deaths in the first month of life. Exposures were antenatal iron/folic acid supplementation and postnatal care from days 1 to 7. Potential confounders were community, socio-economic status and birthing characteristics and perinatal healthcare. Cox regression was used to assess the association between study factors and neonatal mortality. Results Postnatal care services were not associated with newborn survival. Postnatal care on days 1–7 after birth did not reduce neonatal death (HR=1.00, 95% CI 0.55 to 1.83, p=1.00) and early postnatal care on day 1 was associated with an increased risk of early neonatal death (HR=1.27, 95% CI 0.69 to 2.32, p=0.44) possibly reflecting referral of ill newborns. Early postnatal care on day 1 was not protective for neonatal deaths on days 2–7 whether provided by doctors (HR 3.61, 95% CI 1.54 to 8.45, p<0.01), or by midwives or nurses (HR 1.38, 95% CI 0.53 to 3.57, p=0.512). In mothers who took iron/folic acid supplements during pregnancy, the risk of early neonatal death was reduced by 51% (HR=0.49, 95% CI 0.30 to 0.79, p<0.01). Conclusions We found no protective effect of postnatal care against neonatal deaths in Indonesia. However, important reductions in the risk of neonatal death were found for women who reported use of antenatal iron

Sex-dependent role of vesicular glutamate transporter 3 in stress-regulation and related anxiety phenotype during the early postnatal period.

PubMed

Balázsfi, Diána; Farkas, Lívia; Csikota, Péter; Fodor, Anna; Zsebők, Sándor; Haller, József; Zelena, Dóra

2016-07-01

Stress and related disorders are in the focus of interest and glutamate is one of the most important neurotransmitters that can affect these processes. Glutamatergic neurons are characterized by vesicular glutamate transporters (VGluT1-3) among which vGluT3 is unique contributing to the non-canonical, neuromodulatory effect of glutamate. We aimed to study the role of vGluT3 in stress axis regulation and related anxiety during the early postnatal period using knockout (KO) mice with special focus on sex differences. Anxiety was explored on postnatal day (PND) 7-8 by maternal separation-induced ultrasonic vocalization (USV). Stress-hormone levels were detected 60 min after intraperitoneal lipopolysaccharide (LPS) injection 7 days later. Both genotypes gained weight, but on PND 14-15 KO mice pups had smaller body weight compared to wild type (WT). vGluT3 KO mice reacted to an immune stressor with enhanced adrenocorticotropin (ACTH) and corticosterone secretion compared to WT. Although there was a tendency for enhanced anxiety measured by more emitted USV, this did not reach the level of significance. The only sex-related effect was the enhanced corticosterone reactivity in male pups. For the HPA axis regulation in neonates vGluT3 expression seems to be dispensable under basal conditions, but is required for optimal response to immune stressors, most probably through an interaction with other neurotransmitters. Disturbance of the fine balance between these systems may result in a borderline enhanced anxiety-like behavior in vGluT3 KO pups.

The Analysis of Cell Population Dynamics in Mammary Gland Development and Tumorigenesis

DTIC Science & Technology

2005-08-01

AD Award Number: DAMD17-03-1-0498 TITLE: The Analysis of Cell Population Dynamics in Mammary Gland Development and Tumorigenesis PRINCIPAL...Summary 1 Aug 2004 - 31 Jul 2005 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER The Analysis of Cell Population Dynamics in Mammary Gland Development and...STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The mammary gland is made up of several epithelial cell

From genes to milk: genomic organization and epigenetic regulation of the mammary transcriptome.

PubMed

Lemay, Danielle G; Pollard, Katherine S; Martin, William F; Freeman Zadrowski, Courtneay; Hernandez, Joseph; Korf, Ian; German, J Bruce; Rijnkels, Monique

2013-01-01

Even in genomes lacking operons, a gene's position in the genome influences its potential for expression. The mechanisms by which adjacent genes are co-expressed are still not completely understood. Using lactation and the mammary gland as a model system, we explore the hypothesis that chromatin state contributes to the co-regulation of gene neighborhoods. The mammary gland represents a unique evolutionary model, due to its recent appearance, in the context of vertebrate genomes. An understanding of how the mammary gland is regulated to produce milk is also of biomedical and agricultural importance for human lactation and dairying. Here, we integrate epigenomic and transcriptomic data to develop a comprehensive regulatory model. Neighborhoods of mammary-expressed genes were determined using expression data derived from pregnant and lactating mice and a neighborhood scoring tool, G-NEST. Regions of open and closed chromatin were identified by ChIP-Seq of histone modifications H3K36me3, H3K4me2, and H3K27me3 in the mouse mammary gland and liver tissue during lactation. We found that neighborhoods of genes in regions of uniquely active chromatin in the lactating mammary gland, compared with liver tissue, were extremely rare. Rather, genes in most neighborhoods were suppressed during lactation as reflected in their expression levels and their location in regions of silenced chromatin. Chromatin silencing was largely shared between the liver and mammary gland during lactation, and what distinguished the mammary gland was mainly a small tissue-specific repertoire of isolated, expressed genes. These findings suggest that an advantage of the neighborhood organization is in the collective repression of groups of genes via a shared mechanism of chromatin repression. Genes essential to the mammary gland's uniqueness are isolated from neighbors, and likely have less tolerance for variation in expression, properties they share with genes responsible for an organism's survival.

ATM is required for SOD2 expression and homeostasis within the mammary gland.

PubMed

Dyer, Lisa M; Kepple, Jessica D; Ai, Lingbao; Kim, Wan-Ju; Stanton, Virginia L; Reinhard, Mary K; Backman, Lindsey R F; Streitfeld, W Scott; Babu, Nivetha Ramesh; Treiber, Nicolai; Scharffetter-Kochanek, Karin; McKinnon, Peter J; Brown, Kevin D

2017-12-01

ATM activates the NF-κB transcriptional complex in response to genotoxic and oxidative stress. The purpose of this study was to examine if the NF-κB target gene and critical antioxidant SOD2 (MnSOD) in cultured mammary epithelium is also ATM-dependent, and what phenotypes arise from deletion of ATM and SOD2 within the mammary gland. SOD2 expression was studied in human mammary epithelial cells and MCF10A using RNAi to knockdown ATM or the NF-κB subunit RelA. To study ATM and SOD2 function in mammary glands, mouse lines containing Atm or Sod2 genes containing LoxP sites were mated with mice harboring Cre recombinase under the control of the whey acidic protein promoter. Quantitative PCR was used to measure gene expression, and mammary gland structure was studied using histology. SOD2 expression is ATM- and RelA-dependent, ATM knockdown renders cells sensitive to pro-oxidant exposure, and SOD mimetics partially rescue this sensitivity. Mice with germline deletion of Atm fail to develop mature mammary glands, but using a conditional knockout approach, we determined that Atm deletion significantly diminished the expression of Sod2. We also observed that these mice (termed Atm Δ/Δ ) displayed a progressive lactation defect as judged by reduced pup growth rate, aberrant lobulo-alveolar structure, diminished milk protein gene expression, and increased apoptosis within lactating glands. This phenotype appears to be linked to dysregulated Sod2 expression as mammary gland-specific deletion of Sod2 phenocopies defects observed in Atm Δ/Δ dams. We conclude that ATM is required to promote expression of SOD2 within the mammary epithelium, and that both ATM and SOD2 play a crucial role in mammary gland homeostasis.

Microenvironments and Signaling Pathways Regulating Early Dissemination, Dormancy, and Metastasis

DTIC Science & Technology

2016-09-01

regulators of branching morphogenesis during mammary gland development 17,18, arguing that normal mammary epithelial cells cooperate with these innate ...CD45+CD11b+F4/80+ cells lacking lymphoid and granulocytic markers (Supplementary Fig.3B). viSNE plots 30 of myelo- monocytic cells (Fig.5A) showed that...cancer cells and how the microenvironment in these primary sites named P-TMEM (Primary Tumor Microenvironment of Metastases) contribute to early

Mammary fibroadenomatous hyperplasia in a young cat attributed to treatment with megestrol acetate

PubMed Central

MacDougall, Lori D.

2003-01-01

A male, neutered cat was presented for lethargy, reluctance to walk, and mammary enlargement after recent treatment with megestrol acetate. Mammary fibroadenomatous hyperplasia was diagnosed on the basis of history, clinical signs, and histopathological findings. Pathogenesis, clinical signs, and treatment options for mammary fibroadenomatous hyperplasia attributed to megestrol acetate treatment are discussed. PMID:12677692

Postnatal epigenetic modification of glucocorticoid receptor gene in preterm infants: a prospective cohort study

PubMed Central

Kantake, Masato; Yoshitake, Hiroshi; Ishikawa, Hitoshi; Araki, Yoshihiko; Shimizu, Toshiaki

2014-01-01

Objective To examine the environmental effects on cytosine methylation of preterm infant's DNA, because early life experiences are considered to influence the physiological and mental health of an individual through epigenetic modification of DNA. Design A prospective cohort study, comparison of epigenetic differences in the glucocorticoid receptor (GR) gene between healthy term and preterm infants. Setting Neonatal Intensive Care Unit in a Japanese University Hospital. Participants A cohort of 40 (20 term and 20 preterm) infants was recruited on the day of birth, and peripheral blood was obtained from each infant at birth and on postnatal day 4. Main outcome measures The methylation rates in the 1-F promoter region of the GR gene using the Mquant method. Results The methylation rate increased significantly between postnatal days 0 and 4 in preterm infants but remained stable in term infants. Thus, the methylation rate was significantly higher in preterm than in term infants at postnatal day 4. Several perinatal parameters were significantly correlated with this change in the methylation rate. Logistic regression analysis revealed that methylation rates at postnatal day 4 predicted the occurrence of later complications that required glucocorticoid administration during the neonatal period. No gene polymorphism was detected within the GR promoter region analysed. Conclusions Although further large-scale studies are needed to detect the environmental factors that explain the difference in epigenetic modification among infants after birth, our data show that the postnatal environment influences epigenetic programming of GR expression through methylation of the GR gene promoter in premature infants, which may result in relative glucocorticoid insufficiency during the postnatal period. PMID:25023132

Early Increases in Superantigen-Specific Foxp3+ Regulatory T Cells during Mouse Mammary Tumor Virus Infection▿ †

PubMed Central

Cabrera, Gabriel; Burzyn, Dalia; Mundiñano, Juliana; Courreges, M. Cecilia; Camicia, Gabriela; Lorenzo, Daniela; Costa, Héctor; Ross, Susan R.; Nepomnaschy, Irene; Piazzon, Isabel

2008-01-01

Mouse mammary tumor virus (MMTV) is a milk-borne betaretrovirus that has developed strategies to exploit and subvert the host immune system. Here, we show in a natural model of MMTV infection that the virus causes early and progressive increases in superantigen (SAg)-specific Foxp3+ regulatory T cells (Treg) in Peyer's patches (PP). These increases were shown to be dependent on the presence of dendritic cells. CD4+ CD25+ T cells from the PP of infected mice preferentially suppress the proliferative response of T cells to SAg-expressing antigen-presenting cells ex vivo. We investigated the influence of the depletion of CD25+ cells at different stages of the infection. When CD25+ cells were depleted before MMTV infection, an increase in the number of PP SAg-cognate Foxp3− T cells was found at day 6 of infection. Since the SAg response is associated with viral amplification, the possibility exists that Treg cells attenuate the increase in viral load at the beginning of the infection. In contrast, depletion of CD25+ cells once the initial SAg response has developed caused a lower viral load, suggesting that at later stages Treg cells may favor viral persistence. Thus, our results indicated that Treg cells play an important and complex role during MMTV infection. PMID:18495774

Biological and genetic properties of the p53 null preneoplastic mammary epithelium

NASA Technical Reports Server (NTRS)

Medina, Daniel; Kittrell, Frances S.; Shepard, Anne; Stephens, L. Clifton; Jiang, Cheng; Lu, Junxuan; Allred, D. Craig; McCarthy, Maureen; Ullrich, Robert L.

2002-01-01

The absence of the tumor suppressor gene p53 confers an increased tumorigenic risk for mammary epithelial cells. In this report, we describe the biological and genetic properties of the p53 null preneoplastic mouse mammary epithelium in a p53 wild-type environment. Mammary epithelium from p53 null mice was transplanted serially into the cleared mammary fat pads of p53 wild-type BALB/c female to develop stable outgrowth lines. The outgrowth lines were transplanted for 10 generations. The outgrowths were ductal in morphology and progressed through ductal hyperplasia and ductal carcinoma in situ before invasive cancer. The preneoplastic outgrowth lines were immortal and exhibited activated telomerase activity. They are estrogen and progesterone receptor-positive, and aneuploid, and had various levels of tumorigenic potential. The biological and genetic properties of these lines are distinct from those found in most hyperplastic alveolar outgrowth lines, the form of mammary preneoplasia occurring in most traditional models of murine mammary tumorigenesis. These results indicate that the preneoplastic cell populations found in this genetically engineered model are similar in biological properties to a subset of precurser lesions found in human breast cancer and provide a unique model to identify secondary events critical for tumorigenicity and invasiveness.

Histochemical properties of bovine and ovine mammary glands during fetal development.

PubMed

Hara, Asuka; Abe, Tomoyuki; Hirao, Atsushi; Sanbe, Kazuhiro; Ayakawa, Hiromichi; Sarantonglaga, Borjigin; Yamaguchi, Mio; Sato, Akane; Khurchabilig, Atchalalt; Ogata, Kazuko; Fukumori, Rika; Sugita, Shoei; Nagao, Yoshikazu

2018-02-20

In order to obtain more information on the development of bovine and ovine fetal mammary glands, a series of mammary glands from fetuses of different ages were analyzed. A total of 16 bovine fetuses with curved crown rump lengths ranging from 12 cm (80 days) to 75 cm (240 days) and 15 ovine fetuses ranging from 55 days to 131 days were examined. We used hematoxylin and eosin stain and Oil-Red-O stain to analyze the developmental and morphogenetic processes of mammary glands. In addition, we used immunohistochemical staining to determine the pattern of expression of cytokeratin 18 (CK18) during luminal epithelial differentiation, α-smooth-muscle actin (α-SMA) for myoepithelial differentiation, Ki-67 for cell proliferation, and estrogen receptor α (ERα). Our analyzes showed: (a) The primary mammary duct begin to proliferate in a lengthwise within the teat at 90 days in bovine fetuses and 63 days in ovine fetus; (b) luminal epithelial cells and myoepithelial cells appeared from 90 days in bovine fetuses and 63 days in ovine fetus; (c) proliferation of epithelial cells appeared to coincide with the development of the primary and secondary ducts; and (d) ERα was not found in the fetal mammary gland, but adipocytes showed the presence of ERα. Overall, these results indicate that the sequence of events in the prenatal development of the mammary gland of sheep is similar to that of cattle.

Histochemical properties of bovine and ovine mammary glands during fetal development

PubMed Central

HARA, Asuka; ABE, Tomoyuki; HIRAO, Atsushi; SANBE, Kazuhiro; AYAKAWA, Hiromichi; SARANTONGLAGA, Borjigin; YAMAGUCHI, Mio; SATO, Akane; KHURCHABILIG, Atchalalt; OGATA, Kazuko; FUKUMORI, Rika; SUGITA, Shoei; NAGAO, Yoshikazu

2017-01-01

In order to obtain more information on the development of bovine and ovine fetal mammary glands, a series of mammary glands from fetuses of different ages were analyzed. A total of 16 bovine fetuses with curved crown rump lengths ranging from 12 cm (80 days) to 75 cm (240 days) and 15 ovine fetuses ranging from 55 days to 131 days were examined. We used hematoxylin and eosin stain and Oil-Red-O stain to analyze the developmental and morphogenetic processes of mammary glands. In addition, we used immunohistochemical staining to determine the pattern of expression of cytokeratin 18 (CK18) during luminal epithelial differentiation, α-smooth-muscle actin (α-SMA) for myoepithelial differentiation, Ki-67 for cell proliferation, and estrogen receptor α (ERα). Our analyzes showed: (a) The primary mammary duct begin to proliferate in a lengthwise within the teat at 90 days in bovine fetuses and 63 days in ovine fetus; (b) luminal epithelial cells and myoepithelial cells appeared from 90 days in bovine fetuses and 63 days in ovine fetus; (c) proliferation of epithelial cells appeared to coincide with the development of the primary and secondary ducts; and (d) ERα was not found in the fetal mammary gland, but adipocytes showed the presence of ERα. Overall, these results indicate that the sequence of events in the prenatal development of the mammary gland of sheep is similar to that of cattle. PMID:29249731

INDUCTION OF MAMMARY GLAND DEVELOPMENT IN ESTROGEN RECEPTOR-ALPHA KNOCKOUT MICE

EPA Science Inventory

Mammary glands from the estrogen receptor knockout ( ERKO) mouse do not undergo ductal morphogenesis or alveolar development. Disrupted Er signaling may result in reduced estrogen-responsive gene products in the mammary gland or reduced mammotropic hormones that contribute t...

Postnatal Brain Growth Assessed by Sequential Cranial Ultrasonography in Infants Born <30 Weeks' Gestational Age.

PubMed

Cuzzilla, R; Spittle, A J; Lee, K J; Rogerson, S; Cowan, F M; Doyle, L W; Cheong, J L Y

2018-06-01

Brain growth in the early postnatal period following preterm birth has not been well described. This study of infants born at <30 weeks' gestational age and without major brain injury aimed to accomplish the following: 1) assess the reproducibility of linear measures made from cranial ultrasonography, 2) evaluate brain growth using sequential cranial ultrasonography linear measures from birth to term-equivalent age, and 3) explore perinatal predictors of postnatal brain growth. Participants comprised 144 infants born at <30 weeks' gestational age at a single center between January 2011 and December 2013. Infants with major brain injury seen on cranial ultrasonography or congenital or chromosomal abnormalities were excluded. Brain tissue and fluid spaces were measured from cranial ultrasonography performed as part of routine clinical care. Brain growth was assessed in 3 time intervals: <7, 7-27, and >27 days' postnatal age. Data were analyzed using intraclass correlation coefficients and mixed-effects regression. A total of 429 scans were assessed for 144 infants. Several linear measures showed excellent reproducibility. All measures of brain tissue increased with postnatal age, except for the biparietal diameter, which decreased within the first postnatal week and increased thereafter. Gestational age of ≥28 weeks at birth was associated with slower growth of the biparietal diameter and ventricular width compared with gestational age of <28 weeks. Postnatal corticosteroid administration was associated with slower growth of the corpus callosum length, transcerebellar diameter, and vermis height. Sepsis and necrotizing enterocolitis were associated with slower growth of the transcerebellar diameter. Postnatal brain growth in infants born at <30 weeks' gestational age can be evaluated using sequential linear measures made from routine cranial ultrasonography and is associated with perinatal predictors of long-term development. © 2018 by American Journal of

Gestational high-fat diet and bisphenol A exposure heightens mammary cancer risk

PubMed Central

Leung, Yuet-Kin; Govindarajah, Vinothini; Cheong, Ana; Veevers, Jennifer; Song, Dan; Gear, Robin; Zhu, Xuegong; Ying, Jun; Kendler, Ady; Medvedovic, Mario; Belcher, Scott

2017-01-01

In utero exposure to bisphenol A (BPA) increases mammary cancer susceptibility in offspring. High-fat diet is widely believed to be a risk factor of breast cancer. The objective of this study was to determine whether maternal exposure to BPA in addition to high-butterfat (HBF) intake during pregnancy further influences carcinogen-induced mammary cancer risk in offspring, and its dose–response curve. In this study, we found that gestational HBF intake in addition to a low-dose BPA (25 µg/kg BW/day) exposure increased mammary tumor incidence in a 50-day-of-age chemical carcinogen administration model and altered mammary gland morphology in offspring in a non-monotonic manner, while shortening tumor-free survival time compared with the HBF-alone group. In utero HBF and BPA exposure elicited differential effects at the gene level in PND21 mammary glands through DNA methylation, compared with HBF intake in the absence of BPA. Top HBF + BPA-dysregulated genes (ALDH1B1, ASTL, CA7, CPLX4, KCNV2, MAGEE2 and TUBA3E) are associated with poor overall survival in The Cancer Genomic Atlas (TCGA) human breast cancer cohort (n = 1082). Furthermore, the prognostic power of the identified genes was further enhanced in the survival analysis of Caucasian patients with estrogen receptor-positive tumors. In conclusion, concurrent HBF dietary and a low-dose BPA exposure during pregnancy increases mammary tumor incidence in offspring, accompanied by alterations in mammary gland development and gene expression, and possibly through epigenetic reprogramming. PMID:28487351

Transforming growth factor-beta regulates mammary carcinoma cell survival and interaction with the adjacent microenvironment.

PubMed

Bierie, Brian; Stover, Daniel G; Abel, Ty W; Chytil, Anna; Gorska, Agnieszka E; Aakre, Mary; Forrester, Elizabeth; Yang, Li; Wagner, Kay-Uwe; Moses, Harold L

2008-03-15

Transforming growth factor (TGF)-beta signaling has been associated with early tumor suppression and late tumor progression; however, many of the mechanisms that mediate these processes are not known. Using Cre/LoxP technology, with the whey acidic protein promoter driving transgenic expression of Cre recombinase (WAP-Cre), we have now ablated the type II TGF-beta receptor (T beta RII) expression specifically within mouse mammary alveolar progenitors. Transgenic expression of the polyoma virus middle T antigen, under control of the mouse mammary tumor virus enhancer/promoter, was used to produce mammary tumors in the absence or presence of Cre (T beta RII((fl/fl);PY) and T beta RII((fl/fl);PY;WC), respectively). The loss of TGF-beta signaling significantly decreased tumor latency and increased the rate of pulmonary metastasis. The loss of TGF-beta signaling was significantly correlated with increased tumor size and enhanced carcinoma cell survival. In addition, we observed significant differences in stromal fibrovascular abundance and composition accompanied by increased recruitment of F4/80(+) cell populations in T beta RII((fl/fl);PY;WC) mice when compared with T beta RII((fl/fl);PY) controls. The recruitment of F4/80(+) cells correlated with increased expression of known inflammatory genes including Cxcl1, Cxcl5, and Ptgs2 (cyclooxygenase-2). Notably, we also identified an enriched K5(+) dNp63(+) cell population in primary T beta RII((fl/fl);PY;WC) tumors and corresponding pulmonary metastases, suggesting that loss of TGF-beta signaling in this subset of carcinoma cells can contribute to metastasis. Together, our current results indicate that loss of TGF-beta signaling in mammary alveolar progenitors may affect tumor initiation, progression, and metastasis through regulation of both intrinsic cell signaling and adjacent stromal-epithelial interactions in vivo.

Postnatal growth standards for preterm infants: the Preterm Postnatal Follow-up Study of the INTERGROWTH-21(st) Project.

PubMed

Villar, José; Giuliani, Francesca; Bhutta, Zulfiqar A; Bertino, Enrico; Ohuma, Eric O; Ismail, Leila Cheikh; Barros, Fernando C; Altman, Douglas G; Victora, Cesar; Noble, Julia A; Gravett, Michael G; Purwar, Manorama; Pang, Ruyan; Lambert, Ann; Papageorghiou, Aris T; Ochieng, Roseline; Jaffer, Yasmin A; Kennedy, Stephen H

2015-11-01

Charts of size at birth are used to assess the postnatal growth of preterm babies on the assumption that extrauterine growth should mimic that in the uterus. The INTERGROWTH-21(st) Project assessed fetal, newborn, and postnatal growth in eight geographically defined populations, in which maternal health care and nutritional needs were met. From these populations, the Fetal Growth Longitudinal Study selected low-risk women starting antenatal care before 14 weeks' gestation and monitored fetal growth by ultrasonography. All preterm births from this cohort were eligible for the Preterm Postnatal Follow-up Study, which included standardised anthropometric measurements, feeding practices based on breastfeeding, and data on morbidity, treatments, and development. To construct the preterm postnatal growth standards, we selected all live singletons born between 26 and before 37 weeks' gestation without congenital malformations, fetal growth restriction, or severe postnatal morbidity. We did analyses with second-degree fractional polynomial regression models in a multilevel framework accounting for repeated measures. Fetal and neonatal data were pooled from study sites and stratified by postmenstrual age. For neonates, boys and girls were assessed separately. From 4607 women enrolled in the study, there were 224 preterm singleton births, of which 201 (90%) were enrolled in the Preterm Postnatal Follow-up Study. Variance component analysis showed that only 0·2% and 4·0% of the total variability in postnatal length and head circumference, respectively, could be attributed to between-site differences, justifying pooling the data from all study sites. Preterm growth patterns differed from those for babies in the INTERGROWTH-21(st) Newborn Size Standards. They overlapped with the WHO Child Growth Standards for term babies by 64 weeks' postmenstrual age. Our data have yielded standards for postnatal growth in preterm infants. These standards should be used for the assessment of

Effects of Postnatal Enriched Environment in a Model of Parkinson's Disease in Adult Rats.

PubMed

Jungling, Adel; Reglodi, Dora; Karadi, Zsofia Nozomi; Horvath, Gabor; Farkas, Jozsef; Gaszner, Balazs; Tamas, Andrea

2017-02-14

Environmental enrichment is a widespread neuroprotective strategy during development and also in the mature nervous system. Several research groups have described that enriched environment in adult rats has an impact on the progression of Parkinson's disease (PD). The aim of our present study was to examine the effects of early, postnatal environmental enrichment after 6-hydroxydopamine-induced (6-OHDA) lesion of the substantia nigra in adulthood. Newborn Wistar rats were divided into control and enriched groups according to their environmental conditions. For environmental enrichment, during the first five postnatal weeks animals were placed in larger cages and exposed to intensive complex stimuli. Dopaminergic cell loss, and hypokinetic and asymmetrical signs were evaluated after inducing PD with unilateral injections of 6-OHDA in three-month-old animals. Treatment with 6-OHDA led to a significant cell loss in the substantia nigra of control animals, however, postnatal enriched circumstances could rescue the dopaminergic cells. Although there was no significant difference in the percentage of surviving cells between 6-OHDA-treated control and enriched groups, the slightly less dopaminergic cell loss in the enriched group compared to control animals resulted in less severe hypokinesia. Our investigation is the first to provide evidence for the neuroprotective effect of postnatal enriched environment in PD later in life.

Effects of milk replacer formulation on measures of mammary growth and composition in Holstein heifers.

PubMed

Daniels, K M; Capuco, A V; McGilliard, M L; James, R E; Akers, R M

2009-12-01

Overfeeding prepubertal heifers may impair mammary parenchymal growth and reduce milk production, but evidence suggests that increased intake of a high-protein milk replacer before weaning may be beneficial. This study was designed to evaluate effects of milk replacer (MR) composition on mass and composition of mammary parenchyma and fat pad, growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis gene expression, and putative mammary epithelial stem cells. Specifically, we hypothesized that positive effects of faster rates of gain during the preweaning period alter the development, persistence, or activity of populations of putative mammary epithelial stem cells, possibly through involvement of GH/IGF-I axis molecules. Twenty-four newborn heifers were fed 1 of 4 MR diets (n = 6/diet): control [20% crude protein (CP), 21% fat MR fed at 441 g of dry matter (DM)/d], high protein, low fat (28% CP, 20% fat MR fed at 951 g of DM/d), high protein, high fat (27% CP, 28% fat MR fed at 951 g of DM/d), and high protein, high fat+ (27% CP, 28% fat MR fed at 1,431 g of DM/d). Water and starter (20% CP, 1.43% fat) were offered ad libitum. Animals were killed on d 65 and mammary tissue was subjected to biochemical, molecular, and histological examination. No differences in mammary parenchymal mass or composition, with or without adjusting for empty body weight, were detected. Mass was increased and composition of the mammary fat pad was altered by nutrient intake. No diet differences in putative mammary epithelial stem cell abundance or abundance of transcripts for genes of the GH/IGF-I axis were detected. In this study, growth of the mammary epithelium, size of the mammary epithelial stem cell population, and components of the GH/IGF-I axis did not depend on diet. However, an underlying positive correlation between telomerase, a marker of mammary stem cells, and growth of the mammary parenchyma was detected. Implications of diet-induced effects on mammary fat pad and

Diagnosis of neonatal ovarian torsion: Emphasis on prenatal and postnatal sonographic findings.

PubMed

Kim, Hyun Su; Yoo, So-Young; Cha, Min Jae; Kim, Ji Hye; Jeon, Tae Yeon; Kim, Wee Kyoung

2016-06-01

Our aim was to retrospectively review the imaging findings of patients with neonatal ovarian torsion, emphasizing prenatal and postnatal sonographic findings. Eleven patients who had had neonatal ovarian torsion diagnosed surgically (n = 9) or clinicoradiologically (n = 2) were enrolled. Prenatal and postnatal sonographic features, including sequential postnatal change, were reviewed. Clinical and pathologic features were also investigated. All patients except one had a fetal ovarian cyst (mean, 5.3 cm) detected on third-trimester sonography, either simple (n = 6) or complex (n = 4). In all 11 patients, initial postnatal sonography had revealed a complex cyst (mean, 4.7 cm) with intracystic clot or debris, the double-wall sign, a fluid-fluid level, and multiple septation. None of the patients had had symptoms or signs related to the ovarian torsion. Follow-up sonography in seven patients had revealed increased echogenicity of the cyst wall with frequent calcification and a decrease in size of the cyst. In two patients, the interval of the change in cyst position was noted, and autoamputation of the torsed ovary had been surgically confirmed. Serous cystadenoma had been identified in one patient. Neonatal ovarian torsion most commonly manifests as an asymptomatic complex cyst on sonography due to torsion of a fetal ovarian cyst. Serial monitoring of a fetal ovarian cyst for its resolution or changes in its appearance is mandatory for making an early diagnosis of torsion. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:290-297, 2016. © 2016 Wiley Periodicals, Inc.

ApcMin, A Mutation in the Murine Apc Gene, Predisposes to Mammary Carcinomas and Focal Alveolar Hyperplasias

NASA Astrophysics Data System (ADS)

Moser, Amy Rapaich; Mattes, Ellen M.; Dove, William F.; Lindstrom, Mary J.; Haag, Jill D.; Gould, Michael N.

1993-10-01

ApcMin (Min, multiple intestinal neoplasia) is a point mutation in the murine homolog of the APC gene. Min/+ mice develop multiple intestinal adenomas, as do humans carrying germ-line mutations in APC. Female mice carrying Min are also prone to develop mammary tumors. Min/+ mammary glands are more sensitive to chemical carcinogenesis than are +/+ mammary glands. Transplantation of mammary cells from Min/+ or +/+ donors into +/+ hosts demonstrates that the propensity to develop mammary tumors is intrinsic to the Min/+ mammary cells. Long-term grafts of Min/+ mammary glands also gave rise to focal alveolar hyperplasias, indicating that the presence of the Min mutation also has a role in the development of these lesions.

Raising gestational choline intake alters gene expression in DMBA-evoked mammary tumors and prolongs survival.

PubMed

Kovacheva, Vesela P; Davison, Jessica M; Mellott, Tiffany J; Rogers, Adrianne E; Yang, Shi; O'Brien, Michael J; Blusztajn, Jan Krzysztof

2009-04-01

Choline is an essential nutrient that serves as a donor of metabolic methyl groups used during gestation to establish the epigenetic DNA methylation patterns that modulate tissue-specific gene expression. Because the mammary gland begins its development prenatally, we hypothesized that choline availability in utero may affect the gland's susceptibility to cancer. During gestational days 11-17, pregnant rats were fed a control, choline-supplemented, or choline-deficient diet (8, 36, and 0 mmol/kg of choline, respectively). On postnatal day 65, the female offspring received 25 mg/kg of a carcinogen 7,12-dimethylbenz[alpha]anthracene. Approximately 70% of the rats developed mammary adenocarcinomas; prenatal diet did not affect tumor latency, incidence, size, and multiplicity. Tumor growth rate was inversely related to choline content in the prenatal diet, resulting in 50% longer survival until euthanasia, determined by tumor size, of the prenatally choline-supplemented rats compared with the prenatally choline-deficient rats. This was accompanied by distinct expression patterns of approximately 70 genes in tumors derived from the three dietary groups. Tumors from the prenatally choline-supplemented rats overexpressed genes that confer favorable prognosis in human cancers (Klf6, Klf9, Nid2, Ntn4, Per1, and Txnip) and underexpressed those associated with aggressive disease (Bcar3, Cldn12, Csf1, Jag1, Lgals3, Lypd3, Nme1, Ptges2, Ptgs1, and Smarcb1). DNA methylation within the tumor suppressor gene, stratifin (Sfn, 14-3-3sigma), was proportional to the prenatal choline supply and correlated inversely with the expression of its mRNA and protein in tumors, suggesting that an epigenetic mechanism may underlie the altered molecular phenotype and tumor growth. Our results suggest a role for adequate maternal choline nutrition during pregnancy in prevention/alleviation of breast cancer in daughters.

Insulin and branched-chain amino acid depletion during mouse preimplantation embryo culture programmes body weight gain and raised blood pressure during early postnatal life.

PubMed

Velazquez, Miguel A; Sheth, Bhavwanti; Smith, Stephanie J; Eckert, Judith J; Osmond, Clive; Fleming, Tom P

2018-02-01

Mouse maternal low protein diet exclusively during preimplantation development (Emb-LPD) is sufficient to programme altered growth and cardiovascular dysfunction in offspring. Here, we use an in vitro model comprising preimplantation culture in medium depleted in insulin and branched-chain amino acids (BCAA), two proposed embryo programming inductive factors from Emb-LPD studies, to examine the consequences for blastocyst organisation and, after embryo transfer (ET), postnatal disease origin. Two-cell embryos were cultured to blastocyst stage in defined KSOM medium supplemented with four combinations of insulin and BCAA concentrations. Control medium contained serum insulin and uterine luminal fluid amino acid concentrations (including BCAA) found in control mothers from the maternal diet model (N-insulin+N-bcaa). Experimental medium (three groups) contained 50% reduction in insulin and/or BCAA (L-insulin+N-bcaa, N-insulin+L-bcaa, and L-insulin+N-bcaa). Lineage-specific cell numbers of resultant blastocysts were not affected by treatment. Following ET, a combined depletion of insulin and BCAA during embryo culture induced a non sex-specific increase in birth weight and weight gain during early postnatal life. Furthermore, male offspring displayed relative hypertension and female offspring reduced heart/body weight, both characteristics of Emb-LPD offspring. Combined depletion of metabolites also resulted in a strong positive correlation between body weight and glucose metabolism that was absent in the control group. Our results support the notion that composition of preimplantation culture medium can programme development and associate with disease origin affecting postnatal growth and cardiovascular phenotypes and implicate two important nutritional mediators in the inductive mechanism. Our data also have implications for human assisted reproductive treatment (ART) practice. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Dietary supplementation with β-hydroxy-β-methylbutyrate calcium during the early postnatal period accelerates skeletal muscle fibre growth and maturity in intra-uterine growth-retarded and normal-birth-weight piglets.

PubMed

Wan, Haifeng; Zhu, Jiatao; Su, Guoqi; Liu, Yan; Hua, Lun; Hu, Liang; Wu, Caimei; Zhang, Ruinan; Zhou, Pan; Shen, Yong; Lin, Yan; Xu, Shengyu; Fang, Zhengfeng; Che, Lianqiang; Feng, Bin; Wu, De

2016-04-01

Intra-uterine growth restriction (IUGR) impairs postnatal growth and skeletal muscle development in neonatal infants. This study evaluated whether dietary β-hydroxy-β-methylbutyrate Ca (HMB-Ca) supplementation during the early postnatal period could improve muscle growth in IUGR neonates using piglets as a model. A total of twelve pairs of IUGR and normal-birth-weight (NBW) male piglets with average initial weights (1·85 (sem 0·36) and 2·51 (sem 0·39) kg, respectively) were randomly allotted to groups that received milk-based diets (CON) or milk-based diets supplemented with 800 mg/kg HMB-Ca (HMB) during days 7-28 after birth. Blood and longissimus dorsi (LD) samples were collected and analysed for plasma amino acid content, fibre morphology and the expression of genes related to muscle development. The results indicate that, regardless of diet, IUGR piglets had a significantly decreased average daily weight gain (ADG) compared with that of NBW piglets (P<0·05). However, IUGR piglets fed HMB-Ca had a net weight and ADG similar to that of NBW piglets fed the CON diet. Irrespective of body weight (BW), HMB-Ca supplementation markedly increased the type II fibre cross-sectional area and the mRNA expression of mammalian target of rapamycin (mTOR), insulin-like growth factor-1 and myosin heavy-chain isoform IIb in the LD of piglets (P<0·05). Moreover, there was a significant interaction between the effects of BW and HMB on mTOR expression in the LD (P<0·05). In conclusion, HMB-Ca supplementation during the early postnatal period could improve skeletal muscle growth and maturity by accelerating fast-twitch glycolytic fibre development in piglets.

Evidence for the essentiality of arachidonic and docosahexaenoic acid in the postnatal maternal and infant diet for the development of the infant's immune system early in life.

PubMed

Richard, Caroline; Lewis, Erin D; Field, Catherine J

2016-05-01

Long-chain polyunsaturated fatty acids (LCPUFA), especially the balance between arachidonic (AA) and docosahexaenoic (DHA) acids are known to have important immunomodulatory roles during the postnatal period when the immune system is rapidly developing. AA and DHA are required in infant formula in many countries but are optional in North America. The rationale for adding these LCPUFA to full-term formula is based on their presence in breast milk and randomized controlled studies that suggest improved cognitive function in preterm infants, but results are more variable in full-term infants. Recently, the European Food Safety Authority has proposed, based on a lack of functional evidence, that AA is not required in infant formula for full-term infants during the first year of life but DHA should remain mandatory. The purpose of this review is to review the evidence from epidemiological and intervention studies regarding the essentiality of AA and DHA in the postnatal infant and maternal diet (breast-feeding) for the immune system development early in life. Although studies support the essentiality of DHA for the immune system development, more research is needed to rule out the essentiality of AA. Nevertheless, intervention studies have demonstrated improvement in many markers of immune function in infants fed formula supplemented with AA and DHA compared with unsupplemented formula, which appears to consistently result in beneficial health outcomes including reduction in the risk of developing allergic and atopic disease early in life.

The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure.

PubMed

Tucker, Deirdre K; Macon, Madisa B; Strynar, Mark J; Dagnino, Sonia; Andersen, Erik; Fenton, Suzanne E

2015-07-01

Perfluorooctanoic acid (PFOA) is a developmental toxicant in mice, with varied strain outcomes depending on dose and period of exposure. The impact of PFOA on female mouse pubertal development at low doses (≤1mg/kg) has yet to be determined. Therefore, female offspring from CD-1 and C57Bl/6 dams exposed to PFOA, creating serum concentrations similar to humans, were examined for pubertal onset, including mammary gland development. Pups demonstrated a shorter PFOA elimination half-life than that reported for adult mice. Prenatal exposure to PFOA caused significant mammary developmental delays in female offspring in both strains. Delays started during puberty and persisted into young adulthood; severity was dose-dependent. Also an evaluation of female serum hormone levels and pubertal timing onset revealed no effects of PFOA compared to controls in either strain. These data suggest that the mammary gland is more sensitive to early low level PFOA exposures compared to other pubertal endpoints, regardless of strain. Published by Elsevier Inc.

Early-life nutritional effects on the female reproductive system.

PubMed

Chan, K A; Tsoulis, M W; Sloboda, D M

2015-02-01

There is now considerable epidemiological and experimental evidence indicating that early-life environmental conditions, including nutrition, affect subsequent development in later life. These conditions induce highly integrated responses in endocrine-related homeostasis, resulting in persistent changes in the developmental trajectory producing an altered adult phenotype. Early-life events trigger processes that prepare the individual for particular circumstances that are anticipated in the postnatal environment. However, where the intrauterine and postnatal environments differ markedly, such modifications to the developmental trajectory may prove maladaptive in later life. Reproductive maturation and function are similarly influenced by early-life events. This should not be surprising, because the primordial follicle pool is established early in life and is thus vulnerable to early-life events. Results of clinical and experimental studies have indicated that early-life adversity is associated with a decline in ovarian follicular reserve, changes in ovulation rates, and altered age at onset of puberty. However, the underlying mechanisms regulating the relationship between the early-life developmental environment and postnatal reproductive development and function are unclear. This review examines the evidence linking early-life nutrition and effects on the female reproductive system, bringing together clinical observations in humans and experimental data from targeted animal models. © 2015 Society for Endocrinology.

Mammary stem cells and the differentiation hierarchy: current status and perspectives

PubMed Central

Visvader, Jane E.; Stingl, John

2014-01-01

The mammary epithelium is highly responsive to local and systemic signals, which orchestrate morphogenesis of the ductal tree during puberty and pregnancy. Based on transplantation and lineage tracing studies, a hierarchy of stem and progenitor cells has been shown to exist among the mammary epithelium. Lineage tracing has highlighted the existence of bipotent mammary stem cells (MaSCs) in situ as well as long-lived unipotent cells that drive morphogenesis and homeostasis of the ductal tree. Moreover, there is accumulating evidence for a heterogeneous MaSC compartment comprising fetal MaSCs, slow-cycling cells, and both long-term and short-term repopulating cells. In parallel, diverse luminal progenitor subtypes have been identified in mouse and human mammary tissue. Elucidation of the normal cellular hierarchy is an important step toward understanding the “cells of origin” and molecular perturbations that drive breast cancer. PMID:24888586

Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol

PubMed Central

CRUZ, PAMELA; TORRES, CRISTIAN; RAMÍREZ, MARÍA EUGENIA; EPUÑÁN, MARÍA JOSÉ; VALLADARES, LUIS EMILIO; SIERRALTA, WALTER DANIEL

2010-01-01

The aim of the present study was to identify the possible mechanisms by which certain estradiol receptor (ER)-positive mammary tumor cells remain resistant to treatment with anti-estrogens or inhibitors of local estradiol (E2) production. To this end, we compared the proliferative effects on mammary cancer cells of the novel selective ER modulator 27-hydroxycholesterol (27OHC) to those of E2, and evaluated their inhibition by ICI 182,780 (ICI). Analysis of the effects on the cell cycle of 27OHC and E2 in the absence or presence of ICI was conducted. In ER-positive mammary tumor cells, we detected the blocking of 27OHC proliferation-stimulatory activity by simvastatin, as well as the inhibition of E2-stimulated proliferation by an α-fetoprotein-derived cyclic nonapeptide. The effects reported herein may be extrapolated to infiltrating mammary cancer, where the activity of local macrophages may stimulate tumor growth. We suggest that increased breast cancer growth in obese patients may be related to increased 27OHC circulatory levels. PMID:22993572

Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol.

PubMed

Cruz, Pamela; Torres, Cristian; Ramírez, María Eugenia; Epuñán, María José; Valladares, Luis Emilio; Sierralta, Walter Daniel

2010-05-01

The aim of the present study was to identify the possible mechanisms by which certain estradiol receptor (ER)-positive mammary tumor cells remain resistant to treatment with anti-estrogens or inhibitors of local estradiol (E(2)) production. To this end, we compared the proliferative effects on mammary cancer cells of the novel selective ER modulator 27-hydroxycholesterol (27OHC) to those of E(2), and evaluated their inhibition by ICI 182,780 (ICI). Analysis of the effects on the cell cycle of 27OHC and E(2) in the absence or presence of ICI was conducted. In ER-positive mammary tumor cells, we detected the blocking of 27OHC proliferation-stimulatory activity by simvastatin, as well as the inhibition of E(2)-stimulated proliferation by an α-fetoprotein-derived cyclic nonapeptide. The effects reported herein may be extrapolated to infiltrating mammary cancer, where the activity of local macrophages may stimulate tumor growth. We suggest that increased breast cancer growth in obese patients may be related to increased 27OHC circulatory levels.

Progesterone receptor isoforms in the mammary gland of cats and dogs.

PubMed

Gracanin, A; de Gier, J; Zegers, K; Bominaar, M; Rutteman, G R; Schaefers-Okkens, A C; Kooistra, H S; Mol, J A

2012-12-01

Progesterone exerts its effect by binding to specific progesterone receptors (PR) within the cell. In dogs and cats, no data are available on PR isoforms as found in other species. We therefore investigated the sequence of the PR gene and encoded protein in dogs and cats, the expression of PR isoforms in mammary tissue using Western blots and the presence of PR in mammary tissue using immunohistochemistry. Comparison of the amino acid sequence of the canine and feline PR with human PR revealed major differences in the PR-B-specific upstream segment (BUS). However, the essential activation function 3 (AF3) domain was intact in the cat but mutated in the dog. The DNA and ligand-binding domains were highly similar among the species. In cats with fibroadenomatous hyperplasia (FAH), high expression of PR mRNA together with growth hormone (GH), GH receptor (GHR) and IGF-I mRNA was found in comparison with feline mammary carcinomas. Immunohistochemical analysis showed strong nuclear as well as cytoplasmic staining for PR in FAH. Western blot analysis revealed expression of the PR-A and PR-B isoforms in the feline mammary gland. In canine mammary tissue, the most abundant PR staining was found in proliferative zones of the mammary gland. Western blot analyses showed mainly staining for PR-A with lower PR-B staining. It is concluded that in dogs and cats both PR isoforms are expressed. The role of mutations found in the canine PR-B is discussed. © 2012 Blackwell Verlag GmbH.

Mosaic analysis of gene function in postnatal mouse brain development by using virus-based Cre recombination.

PubMed

Gibson, Daniel A; Ma, Le

2011-08-01

Normal brain function relies not only on embryonic development when major neuronal pathways are established, but also on postnatal development when neural circuits are matured and refined. Misregulation at this stage may lead to neurological and psychiatric disorders such as autism and schizophrenia. Many genes have been studied in the prenatal brain and found crucial to many developmental processes. However, their function in the postnatal brain is largely unknown, partly because their deletion in mice often leads to lethality during neonatal development, and partly because their requirement in early development hampers the postnatal analysis. To overcome these obstacles, floxed alleles of these genes are currently being generated in mice. When combined with transgenic alleles that express Cre recombinase in specific cell types, conditional deletion can be achieved to study gene function in the postnatal brain. However, this method requires additional alleles and extra time (3-6 months) to generate the mice with appropriate genotypes, thereby limiting the expansion of the genetic analysis to a large scale in the mouse brain. Here we demonstrate a complementary approach that uses virally-expressed Cre to study these floxed alleles rapidly and systematically in postnatal brain development. By injecting recombinant adeno-associated viruses (rAAVs) encoding Cre into the neonatal brain, we are able to delete the gene of interest in different regions of the brain. By controlling the viral titer and coexpressing a fluorescent protein marker, we can simultaneously achieve mosaic gene inactivation and sparse neuronal labeling. This method bypasses the requirement of many genes in early development, and allows us to study their cell autonomous function in many critical processes in postnatal brain development, including axonal and dendritic growth, branching, and tiling, as well as synapse formation and refinement. This method has been used successfully in our own lab

Factors associated with lack of postnatal care among Palestinian women: A cross-sectional study of three clinics in the West Bank

PubMed Central

Dhaher, Enas; Mikolajczyk, Rafael T; Maxwell, Annette E; Krämer, Alexander

2008-01-01

Background Only about one-third of women in Palestine (West Bank and Gaza) obtain postpartum care. Therefore, the goal of this study was to assess factors associated with lack of postnatal care, women's reasons for not obtaining postnatal care, and their attitudes towards its importance. Methods In early 2006, a cross-sectional survey was conducted at three clinics run by the Ministry of Health providing Mother and Child Health Care in West Bank, Palestine. A total of 264 postpartum women attending the clinics were interviewed face-to-face, using a structured questionnaire. Results Although the majority of women considered postnatal care necessary (66.1%), only 36.6% of women obtained postnatal care. The most frequent reason for not obtaining postnatal care was that women did not feel sick and therefore did not need postnatal care (85%), followed by not having been told by their doctor to come back for postnatal care (15.5%). Based on a multivariable analysis, use of postnatal care was higher among women who had experienced problems during their delivery, had a cesarean section, or had an instrumental vaginal delivery than among women who had a spontaneous vaginal delivery. Use of postnatal care was also higher among women who delivered in a private hospital as compared to those who delivered in a public hospital. In addition, we found regional differences. Conclusion The higher use of postnatal care among high-risk women is appropriate, but some clinically dangerous conditions can also occur in low-risk women. Future efforts should therefore focus on providing postnatal care to a larger number of low-risk women. PMID:18638395

Evaluation of serum haptoglobin and C-reactive protein in dogs with mammary tumors.

PubMed

Planellas, Marta; Bassols, Anna; Siracusa, Carlo; Saco, Yolanda; Giménez, Mercè; Pato, Raquel; Pastor, Josep

2009-09-01

In veterinary medicine, there is increasing interest in measuring acute phase proteins as a tool in the diagnosis and monitoring of neoplastic diseases. Although mammary neoplasms are the most common type of cancer in dogs, acute phase proteins have not been extensively evaluated in dogs with mammary tumors. The aim of this study was to evaluate serum haptoglobin (Hp) and C-reactive protein (CRP) concentrations in the dogs with mammary tumors and assess their potential association with malignancy. A retrospective study of dogs with mammary tumors was performed. Serum concentrations of CRP and Hp were determined in healthy control dogs (n=20) and dogs with mammary tumors before surgery (n=41). Mammary tumors were grouped as carcinomas (n=24), fibrosarcoma (n=1), malignant mixed tumors (n=7), benign mixed tumors (n=6), and adenomas (n=3). CRP and Hp concentrations were compared in dogs with different tumor types and were also compared based on tumor size, lymph node infiltration, skin ulceration, fixation to underlying tissue, and time between tumor identification and removal. Hp concentration was significantly (P<.043) higher in dogs with mammary tumors (median 2.03 g/L, range 0.09-2.94 g/L) compared with controls (1.38 g/L, range 0.08-3.00 g/L), but the range of values overlapped considerably. CRP concentration was higher in dogs with carcinomas (4.70 mg/L, range 0.63-128.96 mg/L) vs controls (2.11 mg/L, range 0.25-6.57 mg/L) (P=.0008) and in dogs with ulcerated skin (14.8 mg/L, range 5.7-128.9 mg/L, n=3) compared with those without ulceration (2.4 mg/L, range 0.11-30.3 mg/L, n=38) (P=.048). Serum Hp and CRP do not appear to have value in diagnosing or predicting malignancy of mammary tumors in dogs. Higher CRP concentrations in dogs with mammary carcinoma suggest a role for inflammation in this tumor type.

From Genes to Milk: Genomic Organization and Epigenetic Regulation of the Mammary Transcriptome

PubMed Central

Lemay, Danielle G.; Pollard, Katherine S.; Martin, William F.; Freeman Zadrowski, Courtneay; Hernandez, Joseph; Korf, Ian; German, J. Bruce; Rijnkels, Monique

2013-01-01

Even in genomes lacking operons, a gene's position in the genome influences its potential for expression. The mechanisms by which adjacent genes are co-expressed are still not completely understood. Using lactation and the mammary gland as a model system, we explore the hypothesis that chromatin state contributes to the co-regulation of gene neighborhoods. The mammary gland represents a unique evolutionary model, due to its recent appearance, in the context of vertebrate genomes. An understanding of how the mammary gland is regulated to produce milk is also of biomedical and agricultural importance for human lactation and dairying. Here, we integrate epigenomic and transcriptomic data to develop a comprehensive regulatory model. Neighborhoods of mammary-expressed genes were determined using expression data derived from pregnant and lactating mice and a neighborhood scoring tool, G-NEST. Regions of open and closed chromatin were identified by ChIP-Seq of histone modifications H3K36me3, H3K4me2, and H3K27me3 in the mouse mammary gland and liver tissue during lactation. We found that neighborhoods of genes in regions of uniquely active chromatin in the lactating mammary gland, compared with liver tissue, were extremely rare. Rather, genes in most neighborhoods were suppressed during lactation as reflected in their expression levels and their location in regions of silenced chromatin. Chromatin silencing was largely shared between the liver and mammary gland during lactation, and what distinguished the mammary gland was mainly a small tissue-specific repertoire of isolated, expressed genes. These findings suggest that an advantage of the neighborhood organization is in the collective repression of groups of genes via a shared mechanism of chromatin repression. Genes essential to the mammary gland's uniqueness are isolated from neighbors, and likely have less tolerance for variation in expression, properties they share with genes responsible for an organism's survival

Mouse mammary tumour virus (MMTV) and human breast cancer with neuroendocrine differentiation.

PubMed

Js, Lawson; Cc, Ngan; Wk, Glenn; Dd, Tran

2017-01-01

Mouse mammary tumour viruses (MMTVs) may have a role in a subset of human breast cancers. MMTV positive human breast cancers have similar histological characteristics to neuroendocrine breast cancers and to MMTV positive mouse mammary tumours. The purpose of this study was to investigate the expression of neuroendocrine biomarkers - synaptophysin and chromogranin, to determine if these histological characteristics and biomarker expression were due to the influences of MMTV. Immunohistochemistry analyses to identify synaptophysin and chromogranin were conducted on a series of human breast cancers in which (i) MMTV had been previously identified and had similar histological characteristics to MMTV positive mouse mammary tumours and (ii) MMTV positive mouse mammary tumours. The expression of synaptophysin and chromogranin in MMTV positive mouse mammary tumors were all positive (7 of 7 specimens - 100% positive). The expression of synaptophysin and chromogranin in MMTV positive human breast cancers was much less prevalent (3 of 22 - 14%). There was no expression of synaptophysin and chromogranin in the normal breast tissue control specimens. It is not possible to draw any firm conclusions from these observations. However, despite the small numbers of MMTV positive mouse mammary tumours in this study, the universal expression in these specimens of synaptophysin and chromogranin proteins is striking. This pattern of synaptophysin and chromogranin expression is very different from their expression in MMTV positive human breast cancers. The reason for these differences is not known. The high prevalence of positive expression of synaptophysin and chromogranin in MMTV positive mouse mammary tumours and low expression of synaptophysin and chromogranin in MMTV positive human breast cancers indicates that MMTV is not usually associated with neuroendocrine human breast cancers.

Gestational and Early Postnatal Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants: General Toxicity and Skeletal Variations.

PubMed

Tung, Emily W Y; Yan, Han; Lefèvre, Pavine L C; Berger, Robert G; Rawn, Dorothea F K; Gaertner, Dean W; Kawata, Alice; Rigden, Marc; Robaire, Bernard; Hales, Barbara F; Wade, Michael G

2016-06-01

Brominated flame retardants (BFRs) are stable environmental contaminants known to exert endocrine-disrupting effects. Developmental exposure to polybrominated diphenyl ethers (PBDEs) is correlated with impaired thyroid hormone signaling, as well as estrogenic and anti-androgenic effects. As previous studies have focused on a single congener or technical mixture, the purpose of the current study was to examine the effects of gestational and early postnatal exposure to an environmentally relevant mixture of BFRs designed to reflect house dust levels of PBDEs and hexabromocyclododecane on postnatal developmental outcomes. Pregnant Sprague-Dawley rats were exposed to the PBDE mixture from preconception to weaning (PND 21) through the diet containing 0, 0.75, 250, and 750 mg mixture/kg diet. BFR exposure induced transient reductions in body weight at PND 35 in male and from PND 30-45 in female offspring (250 and 750 mg/kg). Liver weights (PND 21) and xenobiotic metabolizing enzyme activities (PND 21 and 46) were increased in both male and female offspring exposed to 250 and 750 mg/kg diets. Furthermore, serum T4 levels were reduced at PND 21 in both,male and female offspring (250 and 750 mg/kg). At PND 21, Serum alkaline phosphatase (ALP) was decreased in males exposed to 750 mg/kg dietat, and females exposed to 250 and 750 mg/kg diets. At PND 46 ALP was significantly elevated in males (250 and 750 mg/kg). Variations in the cervical vertebrae and phalanges were observed in pups at PND 4 (250 and 750 mg/kg). Therefore, BFR exposure during gestation through to weaning alters developmental programming in the offspring. The persistence of BFRs in the environment remains a cause for concern with regards to developmental toxicity. © 2016 Wiley Periodicals, Inc.

Postnatal depression, eating, exercise, and vomiting before and during pregnancy.

PubMed

Abraham, S; Taylor, A; Conti, J

2001-05-01

To examine the postnatal distress and the eating, exercise, and weight losing behavior of women before and during pregnancy. The subjects were healthy women who had given birth to a singleton healthy baby in the week before the study. They were drawn from two consecutive series of mothers of babies whose birth weights were either < or =2,500 g or >2,500 g. A total of 181 women were interviewed using a standardized interview modified for pregnancy and related behaviors. They also completed the Edinburgh Postnatal Distress Questionnaire. Regression analysis produced a final model containing variables that made a unique contribution to predicting the level of distress of women in the week following childbirth. The model accounted for 25% of the variance and included four variables that were associated with greater distress: fear of weight gain before and during pregnancy, being distracted by thoughts of food during pregnancy, being afraid of gaining more weight than the pregnancy would explain, and vomiting more frequently during the first 3-4 months of pregnancy. A fifth variable accounted for less distress, that is, participating in low-intensity exercise for reasons of shape and weight during months 3-4 of pregnancy. Other variables associated with distress only in the preliminary analysis were maternal age, binge eating, and vomiting before pregnancy. The most distressed mothers were suffering from an eating disorder at the time of pregnancy. The binge and/or purge type of eating disorder was associated with more distress than a food restriction type. Postnatal distress is associated with body weight and shape concerns, with disordered eating before and during pregnancy, and with vomiting during pregnancy. The protective role of low-intensity exercise during early pregnancy needs to be explored. Women with eating disorders should be considered at risk for postnatal problems. Copyright 2001 by John Wiley & Sons, Inc.

Slower postnatal motor development in infants of mothers with latent toxoplasmosis during the first 18 months of life.

PubMed

Kaňková, Sárka; Sulc, Jan; Křivohlavá, Romana; Kuběna, Aleš; Flegr, Jaroslav

2012-11-01

Toxoplasmosis, a zoonosis caused by a protozoan, Toxoplasma gondii, is probably the most widespread human parasitosis in developed countries. Pregnant women with latent toxoplasmosis have seemingly younger fetuses especially in the 16th week of gestation, which suggests that fetuses of Toxoplasma-infected mothers have slower rates of development in the first trimester of pregnancy. In the present retrospective cohort study, we analyzed data on postnatal motor development of infants from 331 questionnaire respondents including 53 Toxoplasma-infected mothers to search for signs of early postnatal development disorders. During the first year of life, a slower postnatal motor development was observed in infants of mothers with latent toxoplasmosis. These infants significantly later developed the ability to control the head position (p=0.039), to roll from supine to prone position (p=0.022) and were slightly later to begin crawling (p=0.059). Our results are compatible with the hypothesis that the difference in the rates of prenatal and early postnatal development between children of Toxoplasma-negative and Toxoplasma-positive mothers might be caused by a decreased stringency of embryo quality control in partly immunosuppressed Toxoplasma-positive mothers resulting in a higher proportion of infants with genetic or developmental disorders in offspring. However, because of relatively low return rate of questionnaires and an associated risk of a sieve effect, our results should be considered as preliminary and performing a large scale prospective study in the future is critically needed. Copyright © 2012 Elsevier Ltd. All rights reserved.

A redefinition of the representation of mammary cells and enzyme activities in a lactating dairy cow model.

PubMed

Hanigan, M D; Rius, A G; Kolver, E S; Palliser, C C

2007-08-01

The Molly model predicts various aspects of digestion and metabolism in the cow, including nutrient partitioning between milk and body stores. It has been observed previously that the model underpredicts milk component yield responses to nutrition and consequently overpredicts body energy store responses. In Molly, mammary enzyme activity is represented as an aggregate of mammary cell numbers and activity per cell with minimal endocrine regulation. Work by others suggests that mammary cells can cycle between active and quiescent states in response to various stimuli. Simple models of milk production have demonstrated the utility of this representation when using the model to simulate variable milking and nutrient restriction. It was hypothesized that replacing the current representation of mammary cells and enzyme activity in Molly with a representation of active and quiescent cells and improving the representation of endocrine control of cell activity would improve predictions of milk component yield. The static representation of cell numbers was replaced with a representation of cell growth during gestation and early lactation periods and first-order cell death. Enzyme capacity for fat and protein synthesis was assumed to be proportional to cell numbers. Enzyme capacity for lactose synthesis was represented with the same equation form as for cell numbers. Data used for parameter estimation were collected as part of an extended lactation trial. Cows with North American or New Zealand genotypes were fed 0, 3, or 6 kg of concentrate dry matter daily during a 600-d lactation. The original model had root mean square prediction errors of 17.7, 22.3, and 19.8% for lactose, protein, and fat yield, respectively, as compared with values of 8.3, 9.4, and 11.7% for the revised model, respectively. The original model predicted body weight with an error of 19.7% vs. 5.7% for the revised model. Based on these observations, it was concluded that representing mammary synthetic

Association between Prenatal and Postnatal Psychological Distress and Toddler Cognitive Development: A Systematic Review

PubMed Central

2015-01-01

Purpose Maternal psychological distress is one of the most common perinatal complications, affecting up to 25% of pregnant and postpartum women. Research exploring the association between prenatal and postnatal distress and toddler cognitive development has not been systematically compiled. The objective of this systematic review was to determine the association between prenatal and postnatal psychological distress and toddler cognitive development. Methods Articles were included if: a) they were observational studies published in English; b) the exposure was prenatal or postnatal psychological distress; c) cognitive development was assessed from 13 to 36 months; d) the sample was recruited in developed countries; and e) exposed and unexposed women were included. A university-based librarian conducted a search of electronic databases (Embase, CINAHL, Eric, PsycInfo, Medline) (January, 1990-March, 2014). We searched gray literature, reference lists, and relevant journals. Two reviewers independently evaluated titles/abstracts for inclusion, and quality using the Scottish Intercollegiate Guideline Network appraisal tool for observational studies. One reviewer extracted data using a standardized form. Results Thirteen of 2448 studies were included. There is evidence of an association between prenatal and postnatal distress and cognitive development. While variable effect sizes were reported for postnatal associations, most studies reported medium effect sizes for the association between prenatal psychological distress and cognitive development. Too few studies were available to determine the influence of the timing of prenatal exposure on cognitive outcomes. Conclusion Findings support the need for early identification and treatment of perinatal mental health problems as a potential strategy for optimizing toddler cognitive development. PMID:25996151

Association between Prenatal and Postnatal Psychological Distress and Toddler Cognitive Development: A Systematic Review.

PubMed

Kingston, Dawn; McDonald, Sheila; Austin, Marie-Paule; Tough, Suzanne

2015-01-01

Maternal psychological distress is one of the most common perinatal complications, affecting up to 25% of pregnant and postpartum women. Research exploring the association between prenatal and postnatal distress and toddler cognitive development has not been systematically compiled. The objective of this systematic review was to determine the association between prenatal and postnatal psychological distress and toddler cognitive development. Articles were included if: a) they were observational studies published in English; b) the exposure was prenatal or postnatal psychological distress; c) cognitive development was assessed from 13 to 36 months; d) the sample was recruited in developed countries; and e) exposed and unexposed women were included. A university-based librarian conducted a search of electronic databases (Embase, CINAHL, Eric, PsycInfo, Medline) (January, 1990-March, 2014). We searched gray literature, reference lists, and relevant journals. Two reviewers independently evaluated titles/abstracts for inclusion, and quality using the Scottish Intercollegiate Guideline Network appraisal tool for observational studies. One reviewer extracted data using a standardized form. Thirteen of 2448 studies were included. There is evidence of an association between prenatal and postnatal distress and cognitive development. While variable effect sizes were reported for postnatal associations, most studies reported medium effect sizes for the association between prenatal psychological distress and cognitive development. Too few studies were available to determine the influence of the timing of prenatal exposure on cognitive outcomes. Findings support the need for early identification and treatment of perinatal mental health problems as a potential strategy for optimizing toddler cognitive development.

Deficits in adult prefrontal cortex neurons and behavior following early post-natal NMDA antagonist treatment.

PubMed

Coleman, Leon G; Jarskog, L Fredrik; Moy, Sheryl S; Crews, Fulton T

2009-09-01

The prefrontal cortex (PFC) is associated with higher cognitive functions including attention and working memory and has been implicated in the regulation of impulsivity as well as the pathology of complex mental illnesses. N-methyl D-aspartate (NMDA) antagonist treatment with dizocilpine induces cell death which is greatest in the frontal cortex on post-natal day seven (P7), however the long-term structural and behavioral effects of this treatment are unknown. This study investigates both the acute neurotoxicity of P7 dizocilpine and the persistent effects of this treatment on pyramidal cells and parvalbumin interneurons in the adult PFC, a brain region involved in the regulation of impulsivity. Dizocilpine treatment on P7 increased cleaved caspase-3 immunoreactivity (IR) in the PFC on P8. In adult mice (P82), P7 dizocilpine treatment resulted in 50% fewer parvalbumin-positive interneurons (p<0.01) and 42% fewer layer V pyramidal neurons (p<0.01) in the PFC. Double immunohistochemistry revealed cleaved caspase-3 IR in both GAD67 IR interneurons and GAD67 (-) neurons. Following dizocilpine treatment at P7, adults showed reduced time in the center of the open field suggesting increased anxiety-like behavior. These findings indicate that early brain insults affecting glutamatergic neurotransmission lead to persistent brain pathology that could contribute to impulsivity and cognitive dysfunction.

Mammary development, hyperestrogenemia, and hypocortisolemia in a male cat with an adrenal cortical carcinoma.

PubMed

Nadolski, Amy C; Markovich, Jessica E; Jennings, Samuel H; Mahony, Orla M

2016-10-01

A 14-year-old neutered male domestic shorthaired cat was diagnosed with an adrenal cortical carcinoma causing hyperestrogenemia that resulted in mammary hyperplasia and sexual behavior. A right adrenalectomy and mammary gland biopsy were performed. Adrenal cortical neoplasia should be ruled out in any neutered male cat with mammary development and/or exhibiting sexual behavior.

Expression of novel, putative stem cell markers in prepubertal and lactating mammary glands of bovine

USDA-ARS?s Scientific Manuscript database

Mammary stem cells (MaSC) are essential for growth and maintenance of the mammary epithelium. Two main phases of mammary growth include ductal elongation prior to puberty and lobulo-alveolar growth and development during pregnancy. Some studies have utilized morphological characteristics and retenti...

Polyurethane-covered mammary implants: a 12-year experience.

PubMed

Gasperoni, C; Salgarello, M; Gargani, G

1992-10-01

Polyurethane-covered mammary implants are the implants of choice in aesthetic and reconstructive mammary surgery. These implants give very good results in regard to breast contour and consistency, and have a very low complication rate. We present our 12-year experience using polyurethane-covered prostheses. We place the implant mostly in the subglandular or subcutaneous site, and their capsular contracture rate is extremely low (3.3%). Based on our experience, we also review the other complications and side effects occurring with polyurethane prostheses and discuss them in detail.

The contribution of growth hormone to mammary neoplasia

PubMed Central

Perry, Jo K; Mohankumar, Kumarasamypet M; Emerald, B Starling; Mertani, Hichem C; Lobie, Peter E

2008-01-01

While the effects of growth hormone (GH) on longitudinal growth are well established, the observation that GH contributes to neoplastic progression is more recent. Accumulating literature implicates GH-mediated signal transduction in the development and progression of a wide range malignancies including breast cancer. Recently autocrine human GH been demonstrated to be an orthotopically expressed oncogene for the human mammary gland. This review will highlight recent evidence linking GH and mammary carcinoma and discuss GH-antagonism as a potential therapeutic approach for treatment of breast cancer. PMID:18253708

Pre- and postnatal exposure of mice to concentrated urban PM2.5 decreases the number of alveoli and leads to altered lung function at an early stage of life.

PubMed

de Barros Mendes Lopes, Thais; Groth, Espen E; Veras, Mariana; Furuya, Tatiane K; de Souza Xavier Costa, Natalia; Ribeiro Júnior, Gabriel; Lopes, Fernanda Degobbi; de Almeida, Francine M; Cardoso, Wellington V; Saldiva, Paulo Hilario Nascimento; Chammas, Roger; Mauad, Thais

2018-06-04

Gestational exposure to air pollution is associated with negative outcomes in newborns and children. In a previous study, we demonstrated a synergistic negative effect of pre- and postnatal exposure to PM 2.5 on lung development in mice. However, the means by which air pollution affects development of the lung have not yet been identified. In this study, we exposed pregnant BALB/c mice and their offspring to concentrated urban PM 2.5 (from São Paulo, Brazil; target dose 600 μg/m 3 for 1 h daily). Exposure was started on embryonic day 5.5 (E5.5, time of placental implantation). Lung tissue of fetuses and offspring was submitted to stereological and transcriptomic analyses at E14.5 (pseudoglandular stage of lung development), E18.5 (saccular stage) and P40 (postnatal day 40, alveolarized lung). Additionally, lung function and cellularity of bronchoalveolar lavage (BAL) fluid were studied in offspring animals at P40. Compared to control animals that were exposed to filtered air throughout gestation and postnatal life, PM-exposed mice exhibited higher lung elastance and a lower alveolar number at P40 whilst the total lung volume and cellularity of BAL fluid were not affected. Glandular and saccular structures of fetal lungs were not altered upon gestational exposure; transcriptomic signatures, however, showed changes related to DNA damage and its regulation, inflammation and regulation of cell proliferation. A differential expression was validated at E14.5 for the candidates Sox8, Angptl4 and Gas1. Our data substantiate the in utero biomolecular effect of gestational exposure to air pollution and provide first-time stereological evidence that pre- and early life-postnatal exposure compromise lung development, leading to a reduced number of alveoli and an impairment of lung function in the adult mouse. Copyright © 2018 Elsevier Ltd. All rights reserved.

Human Breast Cancer Cells Are Redirected to Mammary Epithelial Cells upon Interaction with the Regenerating Mammary Gland Microenvironment In-Vivo

PubMed Central

Bussard, Karen M.; Smith, Gilbert H.

2012-01-01

Breast cancer is the second leading cause of cancer deaths in the United States. At present, the etiology of breast cancer is unknown; however the possibility of a distinct cell of origin, i.e. a cancer stem cell, is a heavily investigated area of research. Influencing signals from the tissue niche are known to affect stem cells. Literature has shown that cancer cells lose their tumorigenic potential and display ‘normal’ behavior when placed into ‘normal’ ontogenic environments. Therefore, it may be the case that the tissue microenvironment is able to generate signals to redirect cancer cell fate. Previously, we showed that pluripotent human embryonal carcinoma cells could be redirected by the regenerating mammary gland microenvironment to contribute epithelial progeny for ‘normal’ gland development in-vivo. Here, we show that that human metastatic, non-metastatic, and metastasis-suppressed breast cancer cells proliferate and contribute to normal mammary gland development in-vivo without tumor formation. Immunochemistry for human-specific mitochondria, keratin 8 and 14, as well as human-specific milk proteins (alpha-lactalbumin, impregnated transplant hosts) confirmed the presence of human cell progeny. Features consistent with normal mammary gland development as seen in intact hosts (duct, lumen formation, development of secretory acini) were recapitulated in both primary and secondary outgrowths from chimeric implants. These results suggest the dominance of the tissue microenvironment over cancer cell fate. This work demonstrates that cultured human breast cancer cells (metastatic and non-metastatic) respond developmentally to signals generated by the mouse mammary gland microenvironment during gland regeneration in-vivo. PMID:23155468

Maturation of Cerebellar Purkinje Cell Population Activity during Postnatal Refinement of Climbing Fiber Network.

PubMed

Good, Jean-Marc; Mahoney, Michael; Miyazaki, Taisuke; Tanaka, Kenji F; Sakimura, Kenji; Watanabe, Masahiko; Kitamura, Kazuo; Kano, Masanobu

2017-11-21

Neural circuits undergo massive refinements during postnatal development. In the developing cerebellum, the climbing fiber (CF) to Purkinje cell (PC) network is drastically reshaped by eliminating early-formed redundant CF to PC synapses. To investigate the impact of CF network refinement on PC population activity during postnatal development, we monitored spontaneous CF responses in neighboring PCs and the activity of populations of nearby CF terminals using in vivo two-photon calcium imaging. Population activity is highly synchronized in newborn mice, and the degree of synchrony gradually declines during the first postnatal week in PCs and, to a lesser extent, in CF terminals. Knockout mice lacking P/Q-type voltage-gated calcium channel or glutamate receptor δ2, in which CF network refinement is severely impaired, exhibit an abnormally high level of synchrony in PC population activity. These results suggest that CF network refinement is a structural basis for developmental desynchronization and maturation of PC population activity. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications

PubMed Central

Harb, Kawssar; Magrinelli, Elia; Nicolas, Céline S; Lukianets, Nikita; Frangeul, Laura; Pietri, Mariel; Sun, Tao; Sandoz, Guillaume; Grammont, Franck; Jabaudon, Denis; Studer, Michèle; Alfano, Christian

2016-01-01

During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex. Ctip2/Satb2 postnatal co-localization defines two distinct neuronal subclasses projecting either to the contralateral cortex or to the brainstem suggesting that Ctip2/Satb2 co-expression may refine their properties rather than determine their identity. Gain- and loss-of-function approaches reveal that the transcriptional adaptor Lmo4 drives this maturation program through modulation of epigenetic mechanisms in a time- and area-specific manner, thereby indicating that a previously unknown genetic program postnatally promotes the acquisition of final subtype-specific features. DOI: http://dx.doi.org/10.7554/eLife.09531.001 PMID:26814051

Mammary development, hyperestrogenemia, and hypocortisolemia in a male cat with an adrenal cortical carcinoma

PubMed Central

Nadolski, Amy C.; Markovich, Jessica E.; Jennings, Samuel H.; Mahony, Orla M.

2016-01-01

A 14-year-old neutered male domestic shorthaired cat was diagnosed with an adrenal cortical carcinoma causing hyperestrogenemia that resulted in mammary hyperplasia and sexual behavior. A right adrenalectomy and mammary gland biopsy were performed. Adrenal cortical neoplasia should be ruled out in any neutered male cat with mammary development and/or exhibiting sexual behavior. PMID:27708447

Characterization of microRNA profile in mammary tissue of dairy and beef breed heifers.

PubMed

Wicik, Z; Gajewska, M; Majewska, A; Walkiewicz, D; Osińska, E; Motyl, T

2016-02-01

MicroRNAs (miRNAs) are small non-coding RNAs that participate in the regulation of gene expression. Their role during mammary gland development is still largely unknown. In this study, we performed a microarray analysis to identify miRNAs associated with high mammogenic potential of the bovine mammary gland. We identified 54 significantly differentially expressed miRNAs between the mammary tissue of dairy (Holstein-Friesian, HF) and beef (Limousin, LM) postpubertal heifers. Fifty-two miRNAs had higher expression in the mammary tissue of LM heifers. The expression of the top candidate miRNAs (bta-miR-10b, bta-miR-29b, bta-miR-101, bta-miR-375, bta-miR-2285t, bta-miR-146b, bta-let7b, bta-miR-107, bta-miR-1434-3p) identified in the microarray experiment was additionally evaluated by qPCR. Enrichment analyses for targeted genes revealed that the major differences between miRNA expression in the mammary gland of HF versus LM were associated with the regulation of signalling pathways that are crucial for mammary gland development, such as TGF-beta, insulin, WNT and inflammatory pathways. Moreover, a number of genes potentially targeted by significantly differentially expressed miRNAs were associated with the activity of mammary stem cells. These data indicate that the high developmental potential of the mammary gland in dairy cattle, leading to high milk productivity, depends also on a specific miRNA expression pattern. © 2015 Blackwell Verlag GmbH.

Tracking the mammary architectural features and detecting breast cancer with magnetic resonance diffusion tensor imaging.

PubMed

Nissan, Noam; Furman-Haran, Edna; Feinberg-Shapiro, Myra; Grobgeld, Dov; Eyal, Erez; Zehavi, Tania; Degani, Hadassa

2014-12-15

Breast cancer is the most common cause of cancer among women worldwide. Early detection of breast cancer has a critical role in improving the quality of life and survival of breast cancer patients. In this paper a new approach for the detection of breast cancer is described, based on tracking the mammary architectural elements using diffusion tensor imaging (DTI). The paper focuses on the scanning protocols and image processing algorithms and software that were designed to fit the diffusion properties of the mammary fibroglandular tissue and its changes during malignant transformation. The final output yields pixel by pixel vector maps that track the architecture of the entire mammary ductal glandular trees and parametric maps of the diffusion tensor coefficients and anisotropy indices. The efficiency of the method to detect breast cancer was tested by scanning women volunteers including 68 patients with breast cancer confirmed by histopathology findings. Regions with cancer cells exhibited a marked reduction in the diffusion coefficients and in the maximal anisotropy index as compared to the normal breast tissue, providing an intrinsic contrast for delineating the boundaries of malignant growth. Overall, the sensitivity of the DTI parameters to detect breast cancer was found to be high, particularly in dense breasts, and comparable to the current standard breast MRI method that requires injection of a contrast agent. Thus, this method offers a completely non-invasive, safe and sensitive tool for breast cancer detection.

Precocious mammary development in an 8-month-old Holstein heifer

PubMed Central

Ambrose, Divakar J.; Emmanuel, Daya G.V.

2008-01-01

An 8-month-old, virgin Holstein heifer with precocious mammary development was presented for examination. Protein, fat, and lactose in the mammary secretion were 14.90%, 0.12%, and 0.20%, respectively; somatic cell count was 3.9 × 106/mL, with no bacterial infection. The heifer was inseminated at 15 months of age, confirmed pregnant, and subsequently slaughtered. PMID:18978977

From antenatal to postnatal depression: associated factors and mitigating influences.

PubMed

Redshaw, Maggie; Henderson, Jane

2013-06-01

Postnatal depression has a serious impact on new mothers and their children and families. Risk factors identified include a history of depression, multiparity, and young age. The study aimed to investigate factors associated with experiencing antenatal depression and developing subsequent postnatal depression. The study utilized survey data from 5332 women about their experience and well-being during pregnancy, in labor, and postnatally up to 3 months. Prespecified sociodemographic and clinical variables were tabulated against the incidence of antenatal depression and postnatal depression. Binary logistic regression was used to estimate the effects of the principal underlying variables. Risk factors for antenatal depression were multiparity, black and minority ethnic (BME) status, physical or mental health problems, living in a deprived area, and unplanned pregnancy. Different factors for postnatal depression were evident among women who had experienced antenatal depression: multiparity and BME status were protective, whereas being left alone in labor and experiencing poor postnatal health increased the risk of postnatal depression. This study confirms previous research on risk factors for antenatal depression and stresses the importance of continuous support in labor and vigilance in the postnatal period regarding the potential ill effects of continuing postnatal health problems.

Validation of a recombinant human bactericidal/permeability-increasing protein (hBPI) expression vector using murine mammary gland tumor cells and the early development of hBPI transgenic goat embryos.

PubMed

Gui, Tao; Liu, Xing; Tao, Jia; Chen, Jianwen; Li, Yunsheng; Zhang, Meiling; Wu, Ronghua; Zhang, Yuanliang; Peng, Kaisong; Liu, Ya; Zhang, Xiaorong; Zhang, Yunhai

2013-12-01

Human bactericidal/permeability-increasing protein (hBPI) is the only antibacterial peptide which acts against both gram-negative bacteria and neutralizes endotoxins in human polymorphonuclear neutrophils; therefore, hBPI is of great value in clinical applications. In the study, we constructed a hBPI expression vector (pBC1-Loxp-Neo-Loxp-hBPI) containing the full-length hBPI coding sequence which could be specifically expressed in the mammary gland. To validate the function of the vector, in vitro cultured C127 (mouse mammary Carcinoma Cells) were transfected with the vector, and the transgenic cell clones were selected to express hBPI by hormone induction. The mRNA and protein expression of hBPI showed that the constructed vector was effective and suitable for future application in producing mammary gland bioreactor. Then, female and male goat fibroblasts were transfected with the vector, and two male and two female transgenic clonal cell lines were obtained. Using the transgenic cell lines as nuclear donors for somatic cell nuclear transfer, the reconstructed goat embryos produced from all four clones could develop to blastocysts in vitro. In conclusion, we constructed and validated an efficient mammary gland-specific hBPI expression vector, pBC1-Loxp-Neo-Loxp-hBPI, and transgenic hBPI goat embryos were successfully produced, laying foundations for future production of recombinant hBPI in goat mammary gland. Copyright © 2013 Elsevier B.V. All rights reserved.

Changes in fine structure of pericytes and novel desmin-immunopositive perivascular cells during postnatal development in rat anterior pituitary gland.

PubMed

Jindatip, Depicha; Fujiwara, Ken; Horiguchi, Kotaro; Tsukada, Takehiro; Kouki, Tom; Yashiro, Takashi

2013-09-01

Pericytes are perivascular cells associated with capillaries. We previously demonstrated that pericytes, identified by desmin immunohistochemistry, produce type I and III collagens in the anterior pituitary gland of adult rats. In addition, we recently used desmin immunoelectron microscopy to characterize a novel type of perivascular cell, dubbed a desmin-immunopositive perivascular cell, in the anterior pituitary. These two types of perivascular cells differ in fine structure. The present study attempted to characterize the morphological features of pituitary pericytes and novel desmin-immunopositive perivascular cells during postnatal development, in particular their role in collagen synthesis. Desmin immunostaining revealed numerous perivascular cells at postnatal day 5 (P5) and P10. Transmission electron microscopy showed differences in the fine structure of the two cell types, starting at P5. Pericytes had well-developed rough endoplasmic reticulum and Golgi apparatus at P5 and P10. The novel desmin-immunopositive perivascular cells exhibited dilated cisternae of rough endoplasmic reticulum at P5-P30. In addition, during early postnatal development in the gland, a number of type I and III collagen-expressing cells were observed, as were high expression levels of these collagen mRNAs. We conclude that pituitary pericytes and novel desmin-immunopositive perivascular cells contain well-developed cell organelles and that they actively synthesize collagens during the early postnatal period.

DNA Methylation Status of the Estrogen Receptor α Gene in Canine Mammary Tumors.

PubMed

Brandão, Yara de Oliveira; Toledo, Mariana Busato; Chequin, Andressa; Cristo, Thierry Grima; Sousa, Renato Silva; Ramos, Edneia Amancio Souza; Klassen, Giseli

2018-01-01

Estrogen receptor α (ERα) has an important role in mammary carcinogenesis, prognosis, and treatment. In human and canine mammary cancer, the most aggressive tumors show loss of ERα expression, which in human breast cancer has been attributed to methylation of the cytosine followed by guanine (CpG) island within the estrogen receptor α gene ( ESR1) promoter. This study aimed to investigate the role of ESR1 CpG island (CGI) methylation in ERα expression in canine mammary tumors. Twenty-one canine mammary samples were sorted into three groups: malignant tumor (n = 9), benign tumor (n = 8), and normal gland (n = 4). Immunohistochemical analysis and reverse-transcription quantitative real-time PCR were performed to assess ERα expression and ESR1 mRNA levels. The methylation status was determined using sodium-bisulfite-treated DNA sequencing. All normal mammary glands and benign tumors showed high ERα expression (score range, 5-8). Six of the nine malignant tumors did not show ERα expression (score 0), two had score 2, and one had score 4. Lower ERα ( P < .005) and ESR1 mRNA levels ( P < .005) were found in malignant mammary tumors than in the other two groups. Canine ESR1 has an intragenic and non-promoter-associated CGI, different from humans. No significant variation in methylation percentage was observed among the groups, suggesting that ESR1 is not regulated by DNA methylation, unlike that in humans. This difference should be considered in further research using ERα as a biomarker for mammary tumors in canine studies on ERα-targeting therapy.

Early Life Stages

EPA Pesticide Factsheets

Childhood should be viewed as a sequence of lifestages, from birth through infancy and adolescence. When assessing early life risks, consideration is given to risks resulting from fetal exposure via the pregnant mother, as well as postnatal exposures.

Postnatal TLR2 activation impairs learning and memory in adulthood.

PubMed

Madar, Ravit; Rotter, Aviva; Waldman Ben-Asher, Hiba; Mughal, Mohamed R; Arumugam, Thiruma V; Wood, W H; Becker, K G; Mattson, Mark P; Okun, Eitan

2015-08-01

Neuroinflammation in the central nervous system is detrimental for learning and memory, as evident form epidemiological studies linking developmental defects and maternal exposure to harmful pathogens. Postnatal infections can also induce neuroinflammatory responses with long-term consequences. These inflammatory responses can lead to motor deficits and/or behavioral disabilities. Toll like receptors (TLRs) are a family of innate immune receptors best known as sensors of microbial-associated molecular patterns, and are the first responders to infection. TLR2 forms heterodimers with either TLR1 or TLR6, is activated in response to gram-positive bacterial infections, and is expressed in the brain during embryonic development. We hypothesized that early postnatal TLR2-mediated neuroinflammation would adversely affect cognitive behavior in the adult. Our data indicate that postnatal TLR2 activation affects learning and memory in adult mice in a heterodimer-dependent manner. TLR2/6 activation improved motor function and fear learning, while TLR2/1 activation impaired spatial learning and enhanced fear learning. Moreover, developmental TLR2 deficiency significantly impairs spatial learning and enhances fear learning, stressing the involvement of the TLR2 pathway in learning and memory. Analysis of the transcriptional effects of TLR2 activation reveals both common and unique transcriptional programs following heterodimer-specific TLR2 activation. These results imply that adult cognitive behavior could be influenced in part, by activation or alterations in the TLR2 pathway at birth. Copyright © 2015 Elsevier Inc. All rights reserved.

Nervous glucose sensing regulates postnatal β cell proliferation and glucose homeostasis

PubMed Central

Tarussio, David; Metref, Salima; Seyer, Pascal; Mounien, Lourdes; Vallois, David; Magnan, Christophe; Foretz, Marc; Thorens, Bernard

2013-01-01

How glucose sensing by the nervous system impacts the regulation of β cell mass and function during postnatal development and throughout adulthood is incompletely understood. Here, we studied mice with inactivation of glucose transporter 2 (Glut2) in the nervous system (NG2KO mice). These mice displayed normal energy homeostasis but developed late-onset glucose intolerance due to reduced insulin secretion, which was precipitated by high-fat diet feeding. The β cell mass of adult NG2KO mice was reduced compared with that of WT mice due to lower β cell proliferation rates in NG2KO mice during the early postnatal period. The difference in proliferation between NG2KO and control islets was abolished by ganglionic blockade or by weaning the mice on a carbohydrate-free diet. In adult NG2KO mice, first-phase insulin secretion was lost, and these glucose-intolerant mice developed impaired glucagon secretion when fed a high-fat diet. Electrophysiological recordings showed reduced parasympathetic nerve activity in the basal state and no stimulation by glucose. Furthermore, sympathetic activity was also insensitive to glucose. Collectively, our data show that GLUT2-dependent control of parasympathetic activity defines a nervous system/endocrine pancreas axis that is critical for β cell mass establishment in the postnatal period and for long-term maintenance of β cell function. PMID:24334455

Polythelia pilosa: a particular form of accessory mammary tissue.

PubMed

Camacho, F; González-Cámpora, R

1998-01-01

The old Kajawa classification which considered eight possible forms of aberrant mammary tissue has been recently modified into a simpler one that considers this condition only when there is glandular parenchyma or when the aberrant tissue is not a glandular tissue but a nipple, an areola or both. This new classification disregards 'polythelia pilosa' defined as an 'isolated patch of hairs only'. To demonstrate that polythelia pilosa is at least a marker of subjacent accessory mammary tissue and, consequently, that the term should be incorporated into the current classification. Among 72 cases of aberrant or accessory mammary tissue, we have studied 14 cases (7 men and 7 women) that were clinically diagnosed as 'visible isolated patches of hairs, apparently without pigmentation nor structures of areola or nipple'. We excised such isolated patches in 3 women. The histopathological examination showed an acanthotic and hyperpigmented epithelium with central depression closed by keratin plugs; in the dermis there were follicles with hairs surrounded by hypertrophic sebaceous glands. In the deepest portion, abundant secretory glomerules and excretory ducts of apocrine gland type could be observed. Since the biopsy of isolated patches of hairs demonstrated structures of either areolar or apocrine glandular tissue, we think that the term 'polythelia pilosa' should be reinstated into the classification as it is at least a marker of true aberrant mammary structures in men and hirsute women.

Sasa health exerts a protective effect on Her2/NeuN mammary tumorigenesis.

PubMed

Ren, Mingqiang; Reilly, R Todd; Sacchi, Nicoletta

2004-01-01

Bamboo grass leaves of different Sasa species have been widely used in food and medicine in Eastern Asia for hundreds of years. Of special interest are Kumazasa (Sasa senanensis rehder) leaves used to prepare an alkaline extract known as Sasa Health. This extract was reported to inhibit both the development and growth of mammary tumors in a mammary tumor strain of virgin SHN mice (1). We found that Sasa Health exerts a significant protective effect on spontaneous mammary tumorigenesis in another mouse model of human breast cancer, the transgenic FVB-Her2/NeuN mouse model. Two cohorts of Her2/NeuN female mice of different age (eleven-week-old and twenty-four-week-old) chronically treated with Sasa Health in drinking water showed both a delay in the development of tumors and reduced tumor multiplicity. Sasa Health also induced inhibition of mammary duct branching and side bud development in association with reduced angiogenesis. Altogether these findings indicate that Sasa Health contains phytochemicals that can effectively retard spontaneous mammary tumorigenesis.

The Mammary Stem Cell Hierarchy: A Looking Glass into Heterogeneous Breast Cancer Landscapes

PubMed Central

Sreekumar, Amulya; Roarty, Kevin; Rosen, Jeffrey M.

2015-01-01

The mammary gland is a dynamic organ that undergoes extensive morphogenesis during the different stages of embryonic development, puberty, estrus, pregnancy, lactation and involution. Systemic and local cues underlie this constant tissue remodeling and act by eliciting an intricate pattern of responses in the mammary epithelial and stromal cells. Decades of studies utilizing methods such as transplantation and lineage tracing have identified a complex hierarchy of mammary stem cells, progenitors and differentiated epithelial cells that fuel mammary epithelial development. Importantly, these studies have extended our understanding of the molecular crosstalk between cell types, and signaling pathways maintaining normal homeostasis that often are deregulated during tumorigenesis. While several questions remain, this research has many implications for breast cancer. Fundamental among these are the identification of the cells of origin for the multiple subtypes of breast cancer and the understanding of tumor heterogeneity. A deeper understanding of these critical questions will unveil novel breast cancer drug targets and treatment paradigms. In this review, we provide a current overview of normal mammary development and tumorigenesis from a stem cell perspective. PMID:26206777

Morphological and immunohistochemical characterization of spontaneous mammary tumours in European hedgehogs (Erinaceus europaeus).

PubMed

Döpke, C; Fehr, M; Thiele, A; Pohlenz, J; Wohlsein, P

2007-07-01

Mammary tumour samples (11 surgical and five post-mortem) from 16 adult European hedgehogs submitted between 1980 and 2004 were examined. Histologically, the tumours were classified as simple tubulo-papillary carcinomas with local invasive growth. In six cases, tumour cell emboli were present in blood vessels or lymphatic vessels, or both. However, metastasis to regional lymph nodes was found only in one hedgehog. Malignant neoplastic epithelial cells were immunolabelled by antibodies specific for various cytokeratins (CKs), including CK1-8, 10, 13-16, 19 and 20. CK expression did not differ from that in normal mammary gland tissue. CK20 was expressed in the mammary tissue of hedgehogs, in contrast to that of dogs and cats; CK7 immunolabelling, however, which commonly occurs in mammary epithelial cells, was negative. CK20 expression, together with the lack of CK7 as determined by a protein-specific antibody, represented an important difference from the CK profile shown by mammary epithelial cells of other mammalian species, including the dog and cat.

Oxytocin binding sites in bovine mammary tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Xin.

1989-01-01

Oxytocin binding sites were identified and characterized in bovine mammary tissue. ({sup 3}H)-oxytocin binding reached equilibrium by 50 min at 20{degree}C and by 8 hr at 4{degree}C. The half-time of displacement at 20{degree}C was approximately 1 hr. Thyrotropin releasing hormone, adrenocorticotropin, angiotensin I, angiotensin II, pentagastrin, bradykinin, xenopsin and L-valyl-histidyl-L-leucyl-L-threonyl-L-prolyl-L-valyl-L-glutamyl-L-lysine were not competitive. In the presence of 10 nM LiCl, addition of oxytocin to dispersed bovine mammary cells, in which phosphatidylinositol was pre-labelled, caused a time and dose-dependent increase in radioactive inositiol monophosphate incorporation. The possibility that there are distinct vasopressin receptors in bovine mammary tissue was investigated. ({sup 3}H)-vasopressinmore » binding reached equilibrium by 40 min at 20{degree}. The half-time of displacement at 20{degree}C was approximately 1 hr. The ability of the peptides to inhibit ({sup 3}H)-vasopressin binding was: (Thr{sup 4},Gly{sup 7})-oxytocin > Arg{sup 8}-vasopressin > (lys{sup 8})-vasopressin > (Deamino{sup 1},D-arg{sup 8})-vasopressin > oxytocin > d (CH{sub 2}){sub 5}Tyr(Me)AVP.« less

Induction of a Pregnancy-Like Mammary Gland Differentiation by Docosapentaenoic Omega-3 Fatty Acid

DTIC Science & Technology

2008-09-01

xylenes, and stored in methyl salicylate . Morphological Assessment of Mammary Gland—Whole inguinal mammary glands were removed from virgin control as...respectively, defatted in xylenes, and stored in methyl salicylate . Quantitative RT-PCR analyses RNA was isolated and subjected to real time PCR analysis... methylation , and fatty acid analysis were performed as previously described [28,48]. Briefly, an ali- quot of mammary tissue homogenate in a glass

Behavioral analysis of the consequences of chronic blockade of NMDA-type glutamate receptors in the early postnatal period in rats.

PubMed

Latysheva, N V; Raevskii, K S

2003-02-01

Considering data on the possible glutamatergic nature of the pathogenesis of schizophrenia, we attempted to model cognitive derangements in animals by chronic blockade of NMDA glutamate receptors. Wistar rats received daily s.c. injections of the non-competitive NMDA glutamate receptor antagonist MK-801 (0.05 mg/kg) from days 7 to day 49 of postnatal life. One day after the antagonist injections given on days 27 and 28 of life, animals of the experimental group showed decreased levels of spontaneous movement and orientational-investigative activity as compared with controls, where there was no change in the elevated locomotor reaction produced in response to the direct action of MK-801. These animals showed decreases in the level of anxiety (on day 40 of life) and derangement in spatial learning with food reinforcement (days 50-54 of life). It is suggested that early neonatal blockade of NMDA glutamate receptors leads to the development in animals of disturbances to situational perception and assessment of incoming sensory information.

Effects of Chronic Genistein Treatment in Mammary Gland, Uterus, and Vagina

PubMed Central

Rimoldi, Guillermo; Christoffel, Julie; Seidlova-Wuttke, Dana; Jarry, Hubertus; Wuttke, Wolfgang

2007-01-01

Background The isoflavone genistein (GEN) is found in soy (Glycine max) and red clover (Trifolium pratense). The estrogenic activity of GEN is known, and it is widely advertised as a phytoestrogen useful in alleviating climacteric complaints and other postmenopausal disorders. Knowledge of effects of long-term administration of GEN in laboratory animals is scarce, and effects in the uterus and mammary gland after long-term administration have not been studied. The uterus and mammary gland are known to be negatively influenced by estrogens used in hormone therapy. Objectives We administered two doses of GEN [mean daily uptake 5.4 (low) or 54 mg/kg (high) body weight (bw)] orally over a period of 3 months to ovariectomized (ovx) rats and compared the effects with a treatment with two doses of 17β-estradiol [E2; 0.17 (low) or 0.7 mg/kg bw (high)]. Mammary glands, vaginae, and uteri were investigated morphologically and immunohistochemically. We quantified the expression of proliferating cell nuclear antigen (PCNA) and progesterone receptor (PR) in the mammary gland. Results In rats treated with either of the E2 doses or the high GEN dose, we found increased uterine weight, and histologic analysis showed estrogen-induced features in the uteri. In vaginae, either E2 dose or GEN high induced hyperplastic epithelium compared with the atrophic controls. In the mammary gland, E2 (either dose) or GEN increased proliferation and PR expression. Serum levels of luteinizing hormone were decreased by E2 (both doses) but not by GEN. Conclusions In summary, E2 and GEN share many effects in the studied organs, particularly in the vagina, uterus, and mammary gland but not in the hypothalamo/pituitary unit. PMID:18174952

Developmental post-natal stress can alter the effects of pre-natal stress on the adult redox balance.

PubMed

Marasco, Valeria; Spencer, Karen A; Robinson, Jane; Herzyk, Pawel; Costantini, David

2013-09-15

Across diverse vertebrate taxa, stressful environmental conditions during development can shape phenotypic trajectories of developing individuals, which, while adaptive in the short-term, may impair health and survival in adulthood. Regardless, the long-lasting benefits or costs of early life stress are likely to depend on the conditions experienced across differing stages of development. Here, we used the Japanese quail (Coturnix coturnix japonica) to experimentally manipulate exposure to stress hormones in developing individuals. We tested the hypothesis that interactions occurring between pre- and post-natal developmental periods can induce long-term shifts on the adult oxidant phenotype in non-breeding sexually mature individuals. We showed that early life stress can induce long-term alterations in the basal antioxidant defences. The magnitude of these effects depended upon the timing of glucocorticoid exposure and upon interactions between the pre- and post-natal stressful stimuli. We also found differences among tissues with stronger effects in the erythrocytes than in the brain in which the long-term effects of glucocorticoids on antioxidant biomarkers appeared to be region-specific. Recent experimental work has demonstrated that early life exposure to stress hormones can markedly reduce adult survival (Monaghan et al., 2012). Our results suggest that long-term shifts in basal antioxidant defences might be one of the potential mechanisms driving such accelerated ageing processes and that post-natal interventions during development may be a potential tool to shape the effects induced by pre-natally glucococorticoid-exposed phenotypes. Copyright © 2013 Elsevier Inc. All rights reserved.

Formula Milk Supplementation on the Postnatal Ward: A Cross-Sectional Analytical Study

PubMed Central

Biggs, Kirsty V.; Hurrell, Katherine; Matthews, Eleanor

2018-01-01

Breastfeeding rates are low in the UK, where approximately one quarter of infants receive a breastmilk substitute (BMS) in the first week of life. We investigated the reasons for early BMS use in two large maternity units in the UK, in order to understand the reasons for the high rate of early BMS use in this setting. Data were collected through infant feeding records, as well as maternal and midwife surveys in 2016. During 2016, 28% of infants received a BMS supplement prior to discharge from the hospital maternity units with only 10% supplementation being clinically indicated. There was wide variation in BMS initiation rates between different midwives, which was associated with ward environment and midwife educational level. Specific management factors associated with non-clinically indicated initiation of BMS were the absence of skin-to-skin contact within an hour of delivery (p = 0.01), and no attendance at an antenatal breastfeeding discussion (p = 0.01). These findings suggest that risk of initiating a BMS during postnatal hospital stay is largely modifiable. Concordance with UNICEF Baby Friendly 10 steps, attention to specific features of the postnatal ward working environment, and the targeting of midwives and mothers with poor educational status may all lead to improved exclusive breastfeeding rates at hospital discharge. PMID:29757936

Formula Milk Supplementation on the Postnatal Ward: A Cross-Sectional Analytical Study.

PubMed

Biggs, Kirsty V; Hurrell, Katherine; Matthews, Eleanor; Khaleva, Ekaterina; Munblit, Daniel; Boyle, Robert J

2018-05-14

Breastfeeding rates are low in the UK, where approximately one quarter of infants receive a breastmilk substitute (BMS) in the first week of life. We investigated the reasons for early BMS use in two large maternity units in the UK, in order to understand the reasons for the high rate of early BMS use in this setting. Data were collected through infant feeding records, as well as maternal and midwife surveys in 2016. During 2016, 28% of infants received a BMS supplement prior to discharge from the hospital maternity units with only 10% supplementation being clinically indicated. There was wide variation in BMS initiation rates between different midwives, which was associated with ward environment and midwife educational level. Specific management factors associated with non-clinically indicated initiation of BMS were the absence of skin-to-skin contact within an hour of delivery ( p = 0.01), and no attendance at an antenatal breastfeeding discussion ( p = 0.01). These findings suggest that risk of initiating a BMS during postnatal hospital stay is largely modifiable. Concordance with UNICEF Baby Friendly 10 steps, attention to specific features of the postnatal ward working environment, and the targeting of midwives and mothers with poor educational status may all lead to improved exclusive breastfeeding rates at hospital discharge.

Adipose and mammary epithelial tissue engineering.

PubMed

Zhu, Wenting; Nelson, Celeste M

2013-01-01

Breast reconstruction is a type of surgery for women who have had a mastectomy, and involves using autologous tissue or prosthetic material to construct a natural-looking breast. Adipose tissue is the major contributor to the volume of the breast, whereas epithelial cells comprise the functional unit of the mammary gland. Adipose-derived stem cells (ASCs) can differentiate into both adipocytes and epithelial cells and can be acquired from autologous sources. ASCs are therefore an attractive candidate for clinical applications to repair or regenerate the breast. Here we review the current state of adipose tissue engineering methods, including the biomaterials used for adipose tissue engineering and the application of these techniques for mammary epithelial tissue engineering. Adipose tissue engineering combined with microfabrication approaches to engineer the epithelium represents a promising avenue to replicate the native structure of the breast.

Adipose and mammary epithelial tissue engineering

PubMed Central

Zhu, Wenting; Nelson, Celeste M.

2013-01-01

Breast reconstruction is a type of surgery for women who have had a mastectomy, and involves using autologous tissue or prosthetic material to construct a natural-looking breast. Adipose tissue is the major contributor to the volume of the breast, whereas epithelial cells comprise the functional unit of the mammary gland. Adipose-derived stem cells (ASCs) can differentiate into both adipocytes and epithelial cells and can be acquired from autologous sources. ASCs are therefore an attractive candidate for clinical applications to repair or regenerate the breast. Here we review the current state of adipose tissue engineering methods, including the biomaterials used for adipose tissue engineering and the application of these techniques for mammary epithelial tissue engineering. Adipose tissue engineering combined with microfabrication approaches to engineer the epithelium represents a promising avenue to replicate the native structure of the breast. PMID:23628872

Mammary molecular portraits reveal lineage-specific features and progenitor cell vulnerabilities.

PubMed

Casey, Alison E; Sinha, Ankit; Singhania, Rajat; Livingstone, Julie; Waterhouse, Paul; Tharmapalan, Pirashaanthy; Cruickshank, Jennifer; Shehata, Mona; Drysdale, Erik; Fang, Hui; Kim, Hyeyeon; Isserlin, Ruth; Bailey, Swneke; Medina, Tiago; Deblois, Genevieve; Shiah, Yu-Jia; Barsyte-Lovejoy, Dalia; Hofer, Stefan; Bader, Gary; Lupien, Mathieu; Arrowsmith, Cheryl; Knapp, Stefan; De Carvalho, Daniel; Berman, Hal; Boutros, Paul C; Kislinger, Thomas; Khokha, Rama

2018-06-19

The mammary epithelium depends on specific lineages and their stem and progenitor function to accommodate hormone-triggered physiological demands in the adult female. Perturbations of these lineages underpin breast cancer risk, yet our understanding of normal mammary cell composition is incomplete. Here, we build a multimodal resource for the adult gland through comprehensive profiling of primary cell epigenomes, transcriptomes, and proteomes. We define systems-level relationships between chromatin-DNA-RNA-protein states, identify lineage-specific DNA methylation of transcription factor binding sites, and pinpoint proteins underlying progesterone responsiveness. Comparative proteomics of estrogen and progesterone receptor-positive and -negative cell populations, extensive target validation, and drug testing lead to discovery of stem and progenitor cell vulnerabilities. Top epigenetic drugs exert cytostatic effects; prevent adult mammary cell expansion, clonogenicity, and mammopoiesis; and deplete stem cell frequency. Select drugs also abrogate human breast progenitor cell activity in normal and high-risk patient samples. This integrative computational and functional study provides fundamental insight into mammary lineage and stem cell biology. © 2018 Casey et al.

Basic fibroblast growth factor in an animal model of spontaneous mammary tumor progression.

PubMed

Kao, Steven; Mo, Jeffrey; Baird, Andrew; Eliceiri, Brian P

2012-06-01

Although basic fibroblast growth factor (FGF2) was the first pro-angiogenic molecule discovered, it has numerous activities on the growth and differentiation of non-vascular cell types. FGF2 is both stimulatory and inhibitory, depending on the cell type evaluated, the experimental design used and the context in which it is tested. Here, we investigated the effects of manipulating endogenous FGF2 on the development of mammary cancer to determine whether its endogenous contribution in vivo is pro- or anti-tumorigenic. Specifically, we examined the effects of FGF2 gene dosing in a cross between a spontaneous breast tumor model (PyVT+ mice) and FGF2-/- (FGF KO) mice. Using these mice, the onset and progression of mammary tumors was determined. As predicted, female FGF2 WT mice developed mammary tumors starting around 60 days after birth and by 80 days, 100% of FGF2 WT female mice had mammary tumors. In contrast, 80% of FGF2 KO female mice had no palpable tumors until nearly three weeks later (85 days) at times when 100% of the WT cohort was tumor positive. All FGF KO mice were tumor-bearing by 115 days. When we compared the onset of mammary tumor development and the tumor progression curves between FGF het and FGF KO mice, we observed a difference, which suggested a gene dosing effect. Analysis of the tumors demonstrated that there were significant differences in tumor size depending on FGF2 status. The delay in tumor onset supports a functional role for FGF2 in mammary tumor progression, but argues against an essential role for FGF2 in overall mammary tumor progression.

Effects of prenatal and postnatal parent depressive symptoms on adopted child HPA regulation: independent and moderated influences.

PubMed

Laurent, Heidemarie K; Leve, Leslie D; Neiderhiser, Jenae M; Natsuaki, Misaki N; Shaw, Daniel S; Harold, Gordon T; Reiss, David

2013-05-01

This study used a prospective adoption design to investigate effects of prenatal and postnatal parent depressive symptom exposure on child hypothalamic-pituitary-adrenal (HPA) activity and associated internalizing symptoms. Birth mother prenatal symptoms and adoptive mother/father postnatal (9-month, 27-month) symptoms were assessed with the Beck Depression Inventory in a sample of 192 families as part of the Early Growth and Development adoption Study. Child morning/evening cortisol levels and child symptoms of internalizing disorders (according to mother/father report on the Child Behavior Checklist) were assessed at 54 months, and birth mother diurnal cortisol was measured at 48 months postnatal. Hierarchical linear modeling was used to test main effects and interactions of parents' symptoms predicting child cortisol, controlling for birth mother cortisol. Prenatal exposure to birth mother symptoms predicted lower child cortisol (main effect), as did postnatal exposure to adoptive parent symptoms (interaction effects). Adoptive mother 9-month symptoms exacerbated cortisol-lowering effects of both concurrent paternal symptoms and later (27-month) maternal symptoms, and the effect of birth mother cortisol. Lower child cortisol, in turn, was associated with higher child internalizing symptoms. Implications are discussed with respect to the intergenerational transmission of depression risk.

Early postnatal cranial vault reduction and fixation surgery for severe hydrocephalic macrocephaly.

PubMed

Iyer, Rajiv R; Carey, Carolyn M; Rottgers, S Alex; Tetreault, Lisa; Shimony, Nir; Katzenstein, Jennifer; Ruas, Ernesto; Tuite, Gerald F

2018-05-01

OBJECTIVE Infants with severe hydrocephalus and extreme macrocephaly typically undergo CSF diversion early in life, which can result in significant cranial deformity due to CSF overdrainage. In this scenario, overlap of the cranial plates can precede the development of secondary synostosis and/or severe, permanent cranial deformity. As a result, extensive cranial vault remodeling is sometimes undertaken later in life, which is often challenging and has been associated with mortality and a high morbidity rate. The authors have previously described a technique for early postnatal cranial vault reduction and fixation (CVRF), in which the calvarial bones are stabilized using absorbable fixation plates in the neonatal period, in an attempt to facilitate patient positioning, simplify hydrocephalus management, and improve cosmesis. Here, the authors describe their institutional experience managing patients with extreme neonatal hydrocephalus with CSF diversion, with and without CVRF, over the past 12 years. METHODS The authors retrospectively reviewed the charts of infants with extreme hydrocephalus (head circumference > 49 cm) treated at their children's hospital with ventriculoperitoneal shunting, with or without CVRF, between 2005 and 2017. Data collected included age, sex, etiology of hydrocephalus, type of CVRF performed (anterior, posterior, or combined), follow-up duration, orbitofrontal circumference, craniometric measurements, intraoperative blood loss, operative duration, and postoperative complications. Developmental data were collected using the third edition of the Ages and Stages Questionnaire. Photographic imaging was used to demonstrate esthetic outcomes, and family questionnaires were used to evaluate satisfaction with the esthetic outcome. RESULTS Eleven patients with extreme neonatal hydrocephalus underwent CSF shunting; 5 underwent shunting alone and 6 patients underwent shunting and CVRF. For patients who underwent shunting and CVRF, the median age at

Influence of caffeine consumption on 7,12-dimethylbenz(a)anthracene-induced mammary gland tumorigenesis in female rats fed a chemically defined diet containing standard and high levels of unsaturated fat.

PubMed

Welsch, C W; DeHoog, J V

1988-04-15

The effect of caffeine (430-500 mg/liter of drinking water) on the initiation and promotion phases of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary gland tumorigenesis in female Sprague-Dawley rats fed a chemically defined diet containing standard (5%) or high (20%) levels of fat (corn oil) was examined. In the initiation studies, caffeine and the standard or high fat diet treatments were provided for 34 days, from 24-29 days of age to 58-63 days of age. Three days prior to termination of caffeine-fat diet treatments, each rat received a single dose of DMBA. In the promotion studies, caffeine and the standard or high fat diets were provided commencing 3 days after a single dose of DMBA (at 56-61 days of age) and until termination of the study. Caffeine consumption, during the initiation phase significantly (P less than 0.05) reduced mammary carcinoma multiplicity (number of tumors/rat), in rats fed either a standard or high fat diet. In the promotion studies, prolonged consumption of caffeine in rats fed either a standard or high fat diet did not significantly effect mammary carcinoma multiplicity. In the early stages of promotion, an apparent increase in mammary carcinoma multiplicity was observed; this increase in mammary carcinoma multiplicity did not, however, reach the 5% level of statistical probability. When caffeine was administered during both the initiation and promotion phases, no significant effect on mammary carcinoma multiplicity was observed. Treatment of rats during the initiation or promotion phases with caffeinated coffee (via drinking water) mimicked the mammary tumor modulating activities of caffeine. Decaffeinated coffee consumption did not effect either the initiation or promotion phases of this tumorigenic process. In both the initiation and promotion studies, caffeine and/or coffee consumption did not significantly affect the incidence of mammary carcinomas (percentage of rats bearing mammary carcinomas) or the mean latency period of

Lgr4 regulates mammary gland development and stem cell activity through the pluripotency transcription factor Sox2.

PubMed

Wang, Ying; Dong, Jie; Li, Dali; Lai, Li; Siwko, Stefan; Li, Yi; Liu, Mingyao

2013-09-01

The key signaling networks regulating mammary stem cells are poorly defined. The leucine-rich repeat containing G protein-coupled receptor (Lgr) family has been implicated in intestinal, gastric, and epidermal stem cell functions. We investigated whether Lgr4 functions in mammary gland development and mammary stem cells. We found that Lgr4(-/-) mice had delayed ductal development, fewer terminal end buds, and decreased side-branching. Crucially, the mammary stem cell repopulation capacity was severely impaired. Mammospheres from Lgr4(-/-) mice showed decreased Wnt signaling. Wnt3a treatment prevented the adverse effects of Lgr4 loss on organoid formation. Chromatin immunoprecipitation analysis indicated that Sox2 expression was controlled by the Lgr4/Wnt/β-catenin/Lef1 pathway. Importantly, Sox2 overexpression restored the in vivo mammary regeneration potential of Lgr4(-/-) mammary stem cells. Therefore, Lgr4 activates Sox2 to regulate mammary development and stem cell functions via Wnt/β-catenin/Lef1. © AlphaMed Press.

The Role of Endothelin System in Renal Structure and Function during the Postnatal Development of the Rat Kidney.

PubMed

Albertoni Borghese, María F; Ortiz, María C; Balonga, Sabrina; Moreira Szokalo, Rocío; Majowicz, Mónica P

2016-01-01

Renal development in rodents, unlike in humans, continues during early postnatal period. We aimed to evaluate whether the pharmacological inhibition of Endothelin system during this period affects renal development, both at structural and functional level in male and female rats. Newborn rats were treated orally from postnatal day 1 to 20 with vehicle or bosentan (Actelion, 20 mg/kg/day), a dual endothelin receptor antagonist (ERA). The animals were divided in 4 groups: control males, control females, ERA males and ERA females. At day 21, we evaluated renal function, determined the glomerular number by a maceration method and by morphometric analysis and evaluated possible structural renal alterations by three methods: 〈alpha〉-Smooth muscle actin (α-SMA) immunohistochemistry, Masson's trichrome and Sirius red staining. The pharmacological inhibition of Endothelin system with a dual ERA during the early postnatal period of the rat did not leads to renal damage in the kidneys of male and female rats. However, ERA administration decreased the number of glomeruli, the juxtamedullary filtration surface area and the glomerular filtration rate and increased the proteinuria. These effects could predispose to hypertension or renal diseases in the adulthood. On the other hand, these effects were more pronounced in male rats, suggesting that there are sex differences that could be greater later in life. These results provide evidence that Endothelin has an important role in rat renal postnatal development. However these results do not imply that the same could happen in humans, since human renal development is complete at birth.

Reaching Mothers and Babies with Early Postnatal Home Visits: The Implementation Realities of Achieving High Coverage in Large-Scale Programs

PubMed Central

Sitrin, Deborah; Guenther, Tanya; Murray, John; Pilgrim, Nanlesta; Rubayet, Sayed; Ligowe, Reuben; Pun, Bhim; Malla, Honey; Moran, Allisyn

2013-01-01

Background Nearly half of births in low-income countries occur without a skilled attendant, and even fewer mothers and babies have postnatal contact with providers who can deliver preventive or curative services that save lives. Community-based maternal and newborn care programs with postnatal home visits have been tested in Bangladesh, Malawi, and Nepal. This paper examines coverage and content of home visits in pilot areas and factors associated with receipt of postnatal visits. Methods Using data from cross-sectional surveys of women with live births (Bangladesh 398, Malawi: 900, Nepal: 615), generalized linear models were used to assess the strength of association between three factors - receipt of home visits during pregnancy, birth place, birth notification - and receipt of home visits within three days after birth. Meta-analytic techniques were used to generate pooled relative risks for each factor adjusting for other independent variables, maternal age, and education. Findings The proportion of mothers and newborns receiving home visits within three days after birth was 57% in Bangladesh, 11% in Malawi, and 50% in Nepal. Mothers and newborns were more likely to receive a postnatal home visit within three days if the mother received at least one home visit during pregnancy (OR2.18, CI1.46–3.25), the birth occurred outside a facility (OR1.48, CI1.28–1.73), and the mother reported a CHW was notified of the birth (OR2.66, CI1.40–5.08). Checking the cord was the most frequently reported action; most mothers reported at least one action for newborns. Conclusions Reaching mothers and babies with home visits during pregnancy and within three days after birth is achievable using existing community health systems if workers are available; linked to communities; and receive training, supplies, and supervision. In all settings, programs must evaluate what community delivery systems can handle and how to best utilize them to improve postnatal care access. PMID

Physical Confirmation and Comparative Genomics of the Rat Mammary carcinoma susceptibility 3 Quantitative Trait Locus.

PubMed

Le, Saasha; Martin, Zachary C; Samuelson, David J

2017-06-07

Human breast and rat mammary cancer susceptibility are complex phenotypes where complete sets of risk associated loci remain to be identified for both species. We tested multiple congenic rat strains to physically confirm and positionally map rat Mammary carcinoma susceptibility 3 ( Mcs3 )-a mammary cancer resistance allele previously predicted at Rattus norvegicus chromosome 1 ( RNO1 ). The mammary cancer susceptible Wistar Furth (WF) strain was the recipient, and the mammary cancer resistant Copenhagen (Cop) strain was the RNO1 -segment donor for congenics. Inbred WF females averaged 6.3 carcinogen-induced mammary carcinomas per rat. Two WF.Cop congenic strains averaged 2.8 and 3.4 mammary carcinomas per rat, which confirmed Mcs3 as an independently acting allele. Two other WF.Cop congenic strains averaged 6.6 and 8.1 mammary carcinomas per rat, and, thus, did not contain Mcs3 Rat Mcs3 was delimited to 27.8 Mb of RNO1 from rs8149408 to rs105131702 ( RNO1 :143700228-171517317 of RGSC 6.0/rn6). Human genetic variants with p values for association to breast cancer risk below 10 -7 had not been reported for Mcs3 orthologous loci; however, human variants located in Mcs3 -orthologous regions with potential association to risk (10 -7  <  p  < 10 -3 ) were listed in some population-based studies. Further, rat Mcs3 contains sequence orthologous to human 11q13/14 -a region frequently amplified in female breast cancer. We conclude that Mcs3 is an independently acting mammary carcinoma resistance allele. Human population-based, genome-targeted association studies interrogating Mcs3 orthologous loci may yield novel breast cancer risk associated variants and genes. Copyright © 2017 Le et al.

Mammary stem cells: Novel markers and novel approaches to increase lactation efficiency

USDA-ARS?s Scientific Manuscript database

Mammary stem cells (MaSC) provide for net growth, renewal and turnover of mammary epithelial cells, and are therefore potential targets for strategies to increase production efficiency. Appropriate regulation of MaSC can potentially benefit milk yield, persistency, dry period management and tissue r...

Do early postnatal body weight changes contribute to neonatal morbidities in the extremely low birth weight infants.

PubMed

Verma, R; Shibly, S; Fang, H; Pollack, S

2015-01-01

The implications of early postnatal body weight changes (Δbw) in the morbidities related to body fluid metabolism in sick preterm infants in not well investigated. The extremely low birth weight infants (ELBW, birth weight <1000 g) have the highest incidence of such morbidities among all neonates. To determine the relationships between Δbw and neonatal morbidities associated with body fluid metabolism in the ELBW infants. In an observational study, the associations between daily weight changes from birth weight (DΔ bw) and oxygen dependence on postnatal day 28 (BPD28), patent ductus arteriosus (PDA), intraventricular-periventricular hemorrhage (IVH), antenatal steroid (ANS) and gestational age (GA) were evaluated. Maximum weight loss (MΔ bw) was correlated with GA, BPD28 and BPD36 (oxygen dependence on postmenstrual 36 weeks). Pearson's correlation co-efficient and multivariate logistic regressions were performed for analysis. DΔ bw correlated inversely with GA on days 1-8 of life (p <  0.01 for all, 0.06 for DOL 2). DΔ bw was associated with a lower risk of BPD28 on days 6 (OR 0.87, 95% CI 0.76-1), 10 (OR 0.86, 95% CI 0.76-0.98) and 11 (OR 0.87, 95% CI 0.77-0.99); with PDA on days 8-11 (OR ranging between 0.89 to 0.92 for the 4 days, 95% CI 0.83 to 0.99) and with IVH on day 5 (OR 0.93, 95% CI 0.86-1) after controlling for GA. DΔ bw was not identified as risk factor for the tested morbidities. ANS decreased DΔ bw on days 4 (OR 0.88, 95% CI 0.78-1) and 10 (OR 0.9, 95% CI 0.84-1). MΔbw correlated directly with BPD28 (r = 0.3, p = 0.004), which declined after controlling for GA (r = 0.2, p = 0.2). DΔ bw is protective for PDA, BPD28 and IVH, independent of gestational age, whereas, the effects of MΔ bw on BPD are governed by maturation in ELBW infants. ANS decreases DΔbw, which correlates inversely with GA during the first week of life.

Early postnatal maternal deprivation in rats induces memory deficits in adult life that can be reversed by donepezil and galantamine.

PubMed

Benetti, Fernando; Mello, Pâmela Billig; Bonini, Juliana Sartori; Monteiro, Siomara; Cammarota, Martín; Izquierdo, Iván

2009-02-01

Early postnatal maternal deprivation is known to cause long-lasting neurobiological effects. Here, we investigated whether some of the cognitive aspects of these deficits might be related to a disruption of the cholinergic system. Pregnant Wistar rats were individually housed and maintained on a 12:12h light/dark cycle with food and water freely available. The mothers were separated from their pups for 3h per day from postnatal day 1 (PND-1) to PND-10. To do that, the dams were moved to a different cage and the pups maintained in the original home cage, which was transferred to a different room kept at 32 degrees C. After they reached 120-150 days of age, maternal-deprived and non-deprived animals were either sacrificed for brain acetylcholinesterase measurement, or trained and tested in an object recognition task and in a social recognition task as described by Rossato et al. (2007) [Rossato, J.I., Bevilaqua, L. R.M., Myskiw, J.C., Medina, J.H., Izquierdo, I., Cammarota, M. 2007. On the role hippocampal synthesis in the consolidation and reconsolidation of object recognition memory. Learn. Mem. 14, 36-46] and Lévy et al. (2003) [Lévy, F., Melo. A.I., Galef. B.G. Jr., Madden, M., Fleming. A.S. 2003. Complete maternal deprivation affects social, but not spatial, learning in adult rats. Dev. Psychobiol. 43, 177-191], respectively. There was increased acetylcholinesterase activity in hippocampus and perirhinal cortex of the deprived animals. In addition, they showed a clear impairment in memory of the two recognition tasks measured 24h after training. Oral administration of the acetylcholinesterase inhibitors, donepezil or galantamine (1mg/kg) 30min before training reversed the memory impairments caused by maternal deprivation. The findings suggest that maternal deprivation affects memory processing at adulthood through a change in brain cholinergic systems.

Un(MaSC)ing Stem Cell Dynamics in Mammary Branching Morphogenesis.

PubMed

Greenwood, Erin; Wrenn, Emma D; Cheung, Kevin J

2017-02-27

The properties of stem cells that participate in mammary gland branching morphogenesis remain contested. Reporting in Nature, Scheele et al. (2017) establish a model for post-pubertal mammary branching morphogenesis in which position-dependent, lineage-restricted stem cells undergo cell mixing in order to contribute to long-term growth. Copyright © 2017 Elsevier Inc. All rights reserved.

The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure

PubMed Central

Tucker, Deirdre K.; Macon, Madisa B.; Strynar, Mark J.; Dagnino, Sonia; Andersen, Erik; Fenton, Suzanne E.

2015-01-01

Perfluorooctanoic acid (PFOA) is a known developmental toxicant in mice, with varied strain outcomes depending on dose and period of exposure. The impact of PFOA on female mouse pubertal development at low doses (≤1 mg/kg), however, has yet to be determined. Therefore, female offspring from CD-1 and C57Bl/6 dams exposed to PFOA, creating serum concentrations similar to humans, were examined for pubertal onset, including mammary gland development. Mouse pups demonstrated a shorter PFOA elimination half-life than that reported for adult mice. Prenatal exposure to PFOA caused significant mammary developmental delays in exposed female offspring in both strains. Delays started during puberty and persisted into young adulthood; severity was dose-dependent. In contrast, an evaluation of serum hormone levels and pubertal timing onset in the same offspring revealed no effects of PFOA compared to controls in either strain. Therefore, our data suggest that the mammary gland is more sensitive to the effects of early low level PFOA exposures compared to other pubertal endpoints, regardless of strain. PMID:25499722