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768: TNFα suppresses fetal hippocampal neural stem cell (NSC) neurogenesis via bHLH mechanism: potential for offspring cognitive and behavioral sequela
Prematurity, Physiology
www.AJOG.org
AT1-AA inhibitory peptide which was significantly lower than RUPP controls. CONCLUSION: These studies indicate that AT1-AA inhibition, by direct binding or inhibition of lymphocyte communication, significantly improves maternal blood pressure in response to placental ischemia and emphasizes the importance of drug discovery for AT1-AA inhibition for preeclamptic patients.
768 TNFa suppresses fetal hippocampal neural stem cell (NSC) neurogenesis via bHLH mechanism: potential for offspring cognitive and behavioral sequela Mina Desai1, Michael Ross1, Guang Han1, Patrick Shelar1, Marie Beall2 1 Harbor-UCLA Medical Center, Torrance, CA, 2Los Angeles Perinatal Associates, Los Angeles, CA
OBJECTIVE: Maternal inflammation induces maternal, placental and
fetal cytokine responses which may result in fetal central inflammatory responses. As maternal inflammation is associated with offspring cerebral palsy, cognitive limitations, and altered behavior, we postulated that fetal cytokines may impair developmental neurogenesis. Fetal hippocampal NSCs proliferate and ultimately differentiate to neurons and astrocytes to regulate memory and neurobehavior. We determined the effect of TNFa on hippocampal NSC proliferation and neurogenesis, and investigated if TNFa effects were mediated via putative bHLH transcription factors. STUDY DESIGN: Hippocampal NSCs from e20 fetal rats were cultured in complete (proliferation) and differentiating (neurogenesis) media. At day 8 of culture, NSCs were treated with TNFa (0.2, 2, 20 ng/ml) or DMSO (control) for 72h. NSC proliferation was assessed by MTT assay and protein expression (Western) of the NSC marker (nestin). Neurogenesis was assessed by expression of neuronal (Tuj1) or astrocyte (GFAP) cell markers. Mechanisms of TNFa action were explored by assay of bHLH proliferative (Hes1) and proneurogenic (Mash1) factors. RESULTS: TNFa (0.2, 2 and 20ng/ml) exhibited significant dosedependent suppression of NSC proliferation (12, 20, 25%) with proportionate reductions in nestin (0.6, 0.5, 0.4-fold). In neurogenesis studies, TNFa significantly reduced neuronal (Tuj1: 0.9, 0.8, 0.6-fold) and increased astrocyte (GFAP: 1.1, 1.3, 1.4-fold) differentiation. TNFa significantly downregulated Hes1 (0.7, 0.5, 0.4-fold) and upregulated Mash1 (1.0, 1.2, 1.4-fold) expression. CONCLUSION: TNFa suppressed NSC proliferation and promoted preferential differentiation towards astrocyte versus neuronal lineage, with effects likely mediated via Hes1 and Mash1. Inflammationinduced reduction in neurogenesis and increased astrogenesis may have critical consequences for newborn hippocampal function, including cognition and behavior.
Poster Session V
Demographic data, progesterone administration, delivery data and serial cervical length measurement data were collected. The rate of cervical shortening was compared in women with a cerclage (study group) to those without a cerclage (control group). A generalized linear regression model for longitudinal data was used to account for repeated cervical length assessments within women. RESULTS: A total of 540 patients were included, 164 (30.4 %) had a cerclage. Age, parity, gestational age (GA) at delivery, GA at initiation of cervical length measurements, 17-hydroxyprogesterone caproate and vaginal progesterone administration were similar between the 2 groups. The mean GA at delivery was 37 1/7 weeks in the cerclage group and 36 6/7 weeks in the control group. There was no significant difference in the rate of cervical shortening between the cerclage and no cerclage groups (0.8 vs 1 mm per week, P¼0.78) [Figure 1]. CONCLUSION: Cervical shortening among women with cerclage occurs at a similar rate to that found in women without a cerclage who were followed with serial cervical length measurements.
Rate of cervical shortening among cerclage and non-cerclage groups
769 The effect of cerclage on the rate of cervical shortening Daphnie Drassinower1, Joy Vink1, Cara Pessel1, Kavita Vani1, Sara Brubaker1, Noelia Zork1, Cande Ananth1 1 Columbia University Medical Center, Obstetrics and Gynecology, New York, NY
OBJECTIVE: To evaluate whether cerclage affects the rate of cervical
shortening. STUDY DESIGN: All women with singleton pregnancies who had serial cervical lengths (CL) from 2009 to 2012 due to a history of spontaneous preterm delivery (PTD) or an incidental short cervix prior to 24 weeks were identified using our ultrasound database. Patients with major fetal anomalies, missing outcome data, abdominal cerclage, and physical exam-indicated cerclage were excluded.
Supplement to JANUARY 2014 American Journal of Obstetrics & Gynecology
S377
www.AJOG.org
AT1-AA inhibitory peptide which was significantly lower than RUPP controls. CONCLUSION: These studies indicate that AT1-AA inhibition, by direct binding or inhibition of lymphocyte communication, significantly improves maternal blood pressure in response to placental ischemia and emphasizes the importance of drug discovery for AT1-AA inhibition for preeclamptic patients.
768 TNFa suppresses fetal hippocampal neural stem cell (NSC) neurogenesis via bHLH mechanism: potential for offspring cognitive and behavioral sequela Mina Desai1, Michael Ross1, Guang Han1, Patrick Shelar1, Marie Beall2 1 Harbor-UCLA Medical Center, Torrance, CA, 2Los Angeles Perinatal Associates, Los Angeles, CA
OBJECTIVE: Maternal inflammation induces maternal, placental and
fetal cytokine responses which may result in fetal central inflammatory responses. As maternal inflammation is associated with offspring cerebral palsy, cognitive limitations, and altered behavior, we postulated that fetal cytokines may impair developmental neurogenesis. Fetal hippocampal NSCs proliferate and ultimately differentiate to neurons and astrocytes to regulate memory and neurobehavior. We determined the effect of TNFa on hippocampal NSC proliferation and neurogenesis, and investigated if TNFa effects were mediated via putative bHLH transcription factors. STUDY DESIGN: Hippocampal NSCs from e20 fetal rats were cultured in complete (proliferation) and differentiating (neurogenesis) media. At day 8 of culture, NSCs were treated with TNFa (0.2, 2, 20 ng/ml) or DMSO (control) for 72h. NSC proliferation was assessed by MTT assay and protein expression (Western) of the NSC marker (nestin). Neurogenesis was assessed by expression of neuronal (Tuj1) or astrocyte (GFAP) cell markers. Mechanisms of TNFa action were explored by assay of bHLH proliferative (Hes1) and proneurogenic (Mash1) factors. RESULTS: TNFa (0.2, 2 and 20ng/ml) exhibited significant dosedependent suppression of NSC proliferation (12, 20, 25%) with proportionate reductions in nestin (0.6, 0.5, 0.4-fold). In neurogenesis studies, TNFa significantly reduced neuronal (Tuj1: 0.9, 0.8, 0.6-fold) and increased astrocyte (GFAP: 1.1, 1.3, 1.4-fold) differentiation. TNFa significantly downregulated Hes1 (0.7, 0.5, 0.4-fold) and upregulated Mash1 (1.0, 1.2, 1.4-fold) expression. CONCLUSION: TNFa suppressed NSC proliferation and promoted preferential differentiation towards astrocyte versus neuronal lineage, with effects likely mediated via Hes1 and Mash1. Inflammationinduced reduction in neurogenesis and increased astrogenesis may have critical consequences for newborn hippocampal function, including cognition and behavior.
Poster Session V
Demographic data, progesterone administration, delivery data and serial cervical length measurement data were collected. The rate of cervical shortening was compared in women with a cerclage (study group) to those without a cerclage (control group). A generalized linear regression model for longitudinal data was used to account for repeated cervical length assessments within women. RESULTS: A total of 540 patients were included, 164 (30.4 %) had a cerclage. Age, parity, gestational age (GA) at delivery, GA at initiation of cervical length measurements, 17-hydroxyprogesterone caproate and vaginal progesterone administration were similar between the 2 groups. The mean GA at delivery was 37 1/7 weeks in the cerclage group and 36 6/7 weeks in the control group. There was no significant difference in the rate of cervical shortening between the cerclage and no cerclage groups (0.8 vs 1 mm per week, P¼0.78) [Figure 1]. CONCLUSION: Cervical shortening among women with cerclage occurs at a similar rate to that found in women without a cerclage who were followed with serial cervical length measurements.
Rate of cervical shortening among cerclage and non-cerclage groups
769 The effect of cerclage on the rate of cervical shortening Daphnie Drassinower1, Joy Vink1, Cara Pessel1, Kavita Vani1, Sara Brubaker1, Noelia Zork1, Cande Ananth1 1 Columbia University Medical Center, Obstetrics and Gynecology, New York, NY
OBJECTIVE: To evaluate whether cerclage affects the rate of cervical
shortening. STUDY DESIGN: All women with singleton pregnancies who had serial cervical lengths (CL) from 2009 to 2012 due to a history of spontaneous preterm delivery (PTD) or an incidental short cervix prior to 24 weeks were identified using our ultrasound database. Patients with major fetal anomalies, missing outcome data, abdominal cerclage, and physical exam-indicated cerclage were excluded.
Supplement to JANUARY 2014 American Journal of Obstetrics & Gynecology
S377