Search

Your search keyword '"Giussani, Dino A."' showing total 797 results
Start Over Author "Giussani, Dino A."
797 results on '"Giussani, Dino A."'

151. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease

Author

Allison, Beth J., Kaandorp, Joepe J., Kane, Andrew D., Camm, Emily J., Lusby, Ciara, Cross, Christine M., Nevin-Dolan, Rhianon, Thakor, Avnesh S., Derks, Jan B., Tarry-Adkins, Jane L., Ozanne, Susan E., Giussani, Dino A., Ozanne, Susan [0000-0001-8753-5144], Giussani, Dino [0000-0002-1308-1204], and Apollo - University of Cambridge Repository

Subjects
Inflammation, Male, Aging, Antimetabolites, Allopurinol, Rats, Cardiovascular Physiological Phenomena, Research Communication, Oxidative Stress, cell senescence, fetal hypoxia, Cardiovascular Diseases, Pregnancy, Animals, Female, xanthine oxidase, Biomarkers
Abstract

Aging and developmental programming are both associated with oxidative stress and endothelial dysfunction, suggesting common mechanistic origins. However, their interrelationship has been little explored. In a rodent model of programmed cardiovascular dysfunction we determined endothelial function and vascular telomere length in young (4 mo) and aged (15 mo) adult offspring of normoxic or hypoxic pregnancy with or without maternal antioxidant treatment. We show loss of endothelial function [maximal arterial relaxation to acetylcholine (71 ± 3 vs. 55 ± 3%) and increased vascular short telomere abundance (4.2–1.3 kb) 43.0 ± 1.5 vs. 55.1 ± 3.8%) in aged vs. young offspring of normoxic pregnancy (P < 0.05). Hypoxic pregnancy in young offspring accelerated endothelial dysfunction (maximal arterial relaxation to acetylcholine: 42 ± 1%, P < 0.05) but this was dissociated from increased vascular short telomere length abundance. Maternal allopurinol rescued maximal arterial relaxation to acetylcholine in aged offspring of normoxic or hypoxic pregnancy but not in young offspring of hypoxic pregnancy. Aged offspring of hypoxic allopurinol pregnancy compared with aged offspring of untreated hypoxic pregnancy had lower levels of short telomeres (vascular short telomere length abundance 35.1 ± 2.5 vs. 48.2 ± 2.6%) and of plasma proinflammatory chemokine (24.6 ± 2.8 vs. 36.8 ± 5.5 pg/ml, P < 0.05). These data provide evidence for divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease, and aging being decelerated by antioxidants even prior to birth.—Allison, B. J., Kaandorp, J. J., Kane, A. D., Camm, E. J., Lusby, C., Cross, C. M., Nevin-Dolan, R., Thakor, A. S., Derks, J. B., Tarry-Adkins, J. L., Ozanne, S. E., Giussani, D. A. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease.

Published
2016

152. The fetal brain sparing response to hypoxia: physiological mechanisms

Author

Giussani, Dino A, Giussani, Dino [0000-0002-1308-1204], and Apollo - University of Cambridge Repository

Subjects
Vasodilation, Carotid Body, Reflex, Brain, Humans, Fetal Hypoxia, Adaptation, Physiological
Abstract

How the fetus withstands an environment of reduced oxygenation during life in the womb has been a vibrant area of research since this field was introduced by Joseph Barcroft, a century ago. Studies spanning five decades have since used the chronically instrumented fetal sheep preparation to investigate the fetal compensatory responses to hypoxia. This defence is contingent on the fetal cardiovascular system, which in late gestation adopts strategies to decrease oxygen consumption and redistribute the cardiac output away from peripheral vascular beds and towards essential circulations, such as those perfusing the brain. The introduction of simultaneous measurement of blood flow in the fetal carotid and femoral circulations by ultrasonic transducers has permitted investigation of the dynamics of the fetal brain sparing response for the first time. Now we know that major components of fetal brain sparing during acute hypoxia are triggered exclusively by a carotid chemoreflex and that they are modified by endocrine agents and the recently discovered vascular oxidant tone. The latter is determined by the interaction between nitric oxide and reactive oxygen species. The fetal brain sparing response matures as the fetus approaches term, in association with the prepartum increase in fetal plasma cortisol, and treatment of the preterm fetus with clinically relevant doses of synthetic steroids mimics this maturation. Despite intense interest into how the fetal brain sparing response may be affected by adverse intrauterine conditions, this area of research has been comparatively scant, but it is likely to take centre stage in the near future.

Published
2016

154. Neonatal glucocorticoid overexposure alters cardiovascular function in young adult horses in a sex-linked manner.

Author

Valenzuela, Orlando A., Jellyman, Juanita K., Allen, Vanessa L., Niu, Youguo, Holdstock, Nicola B., Forhead, Alison J., Giussani, Dino A., Fowden, Abigail L., and Herrera, Emilio A.

Abstract

Prenatal glucocorticoid overexposure has been shown to programme adult cardiovascular function in a range of species, but much less is known about the long-term effects of neonatal glucocorticoid overexposure. In horses, prenatal maturation of the hypothalamus–pituitary–adrenal axis and the normal prepartum surge in fetal cortisol occur late in gestation compared to other precocious species. Cortisol levels continue to rise in the hours after birth of full-term foals and increase further in the subsequent days in premature, dysmature and maladapted foals. Thus, this study examined the adult cardiovascular consequences of neonatal cortisol overexposure induced by adrenocorticotropic hormone administration to full-term male and female pony foals. After catheterisation at 2–3 years of age, basal arterial blood pressures (BP) and heart rate were measured together with the responses to phenylephrine (PE) and sodium nitroprusside (SNP). These data were used to assess cardiac baroreflex sensitivity. Neonatal cortisol overexposure reduced both the pressor and bradycardic responses to PE in the young adult males, but not females. It also enhanced the initial hypotensive response to SNP, slowed recovery of BP after infusion and reduced the gain of the cardiac baroreflex in the females, but not males. Basal diastolic pressure and cardiac baroreflex sensitivity also differed with sex, irrespective of neonatal treatment. The results show that there is a window of susceptibility for glucocorticoid programming during the immediate neonatal period that alters cardiovascular function in young adult horses in a sex-linked manner. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

156. International Society for Therapeutic Ultrasound Conference 2016

Author

Fowlkes, Brian, Ghanouni, Pejman, Sanghvi, Narendra, Coussios, Constantin, Lyon, Paul C., Gray, Michael, Mannaris, Christophoros, Victor, Marie de Saint, Stride, Eleanor, Cleveland, Robin, Carlisle, Robert, Wu, Feng, Middleton, Mark, Gleeson, Fergus, Aubry, Jean-Franҫois, Pauly, Kim Butts, Moonen, Chrit, Vortman, Jacob, Sharabi, Shirley, Daniels, Dianne, Last, David, Guez, David, Levy, Yoav, Volovick, Alexander, Grinfeld, Javier, Rachmilevich, Itay, Amar, Talia, Zibly, Zion, Mardor, Yael, Harnof, Sagi, Plaksin, Michael, Weissler, Yoni, Shoham, Shy, Kimmel, Eitan, Naor, Omer, Farah, Nairouz, Paeng, Dong-Guk, Xu, Zhiyuan, Snell, John, Quigg, Anders H., Eames, Matthew, Jin, Changzhu, Everstine, Ashli C., Sheehan, Jason P., Lopes, Beatriz S., Kassell, Neal, Looi, Thomas, Khokhlova, Vera, Mougenot, Charles, Hynynen, Kullervo, Drake, James, Slayton, Michael, Amodei, Richard C., Compton, Keegan, McNelly, Ashley, Latt, Daniel, Kearney, John, Melodelima, David, Dupre, Aurelien, Chen, Yao, Perol, David, Vincenot, Jeremy, Chapelon, Jean-Yves, Rivoire, Michel, Guo, Wei, Ren, Guoxin, Shen, Guofeng, Neidrauer, Michael, Zubkov, Leonid, Weingarten, Michael S., Margolis, David J., Lewin, Peter A., McDannold, Nathan, Sutton, Jonathan, Vykhodtseva, Natalia, Livingstone, Margaret, Kobus, Thiele, Zhang, Yong-Zhi, Schwartz, Michael, Huang, Yuexi, Lipsman, Nir, Jain, Jennifer, Chapman, Martin, Sankar, Tejas, Lozano, Andres, Yeung, Robert, Damianou, Christakis, Papadopoulos, Nikolaos, Brokman, Omer, Zadicario, Eyal, Brenner, Ori, Castel, David, Wu, Shih-Ying, Grondin, Julien, Zheng, Wenlan, Heidmann, Marc, Karakatsani, Maria Eleni, Sánchez, Carlos J. Sierra, Ferrera, Vincent, Konofagou, Elisa E., Yiannakou, Marinos, Cho, HongSeok, Lee, Hwayoun, Han, Mun, Choi, Jong-Ryul, Lee, Taekwan, Ahn, Sanghyun, Chang, Yongmin, Park, Juyoung, Ellens, Nicholas, Partanen, Ari, Farahani, Keyvan, Airan, Raag, Carpentier, Alexandre, Canney, Michael, Vignot, Alexandre, Lafon, Cyril, Delattre, Jean-yves, Idbaih, Ahmed, Odéen, Henrik, Bolster, Bradley, Jeong, Eun Kee, Parker, Dennis L., Gaur, Pooja, Feng, Xue, Fielden, Samuel, Meyer, Craig, Werner, Beat, Grissom, William, Marx, Michael, Weber, Hans, Taviani, Valentina, Hargreaves, Brian, Tanaka, Jun, Kikuchi, Kentaro, Ishijima, Ayumu, Azuma, Takashi, Minamihata, Kosuke, Yamaguchi, Satoshi, Nagamune, Teruyuki, Sakuma, Ichiro, Takagi, Shu, Santin, Mathieu D., Marsac, Laurent, Maimbourg, Guillaume, Monfort, Morgane, Larrat, Benoit, François, Chantal, Lehéricy, Stéphane, Tanter, Mickael, Samiotaki, Gesthimani, Wang, Shutao, Acosta, Camilo, Feinberg, Eliza R., Kovacs, Zsofia I., Tu, Tsang-Wei, Papadakis, Georgios Z., Reid, William C., Hammoud, Dima A., Frank, Joseph A., Kovacs, Zsofia i., Kim, Saejeong, Jikaria, Neekita, Bresler, Michele, Qureshi, Farhan, Xia, Jingjing, Tsui, Po-Shiang, Liu, Hao-Li, Plata, Juan C., Sveinsson, Bragi, Salgaonkar, Vasant A., Adams, Matthew, Diederich, Chris, Ozhinsky, Eugene, Bucknor, Matthew D., Rieke, Viola, Mikhail, Andrew, Severance, Lauren, Negussie, Ayele H., Wood, Bradford, de Greef, Martijn, Schubert, Gerald, Ries, Mario, Poorman, Megan E., Dockery, Mary, Chaplin, Vandiver, Dudzinski, Stephanie O., Spears, Ryan, Caskey, Charles, Giorgio, Todd, Costa, Marcia M., Papaevangelou, Efthymia, Shah, Anant, Rivens, Ian, Box, Carol, Bamber, Jeff, ter Haar, Gail, Burks, Scott R., Nagle, Matthew, Nguyen, Ben, Milo, Blerta, Le, Nhan M., Song, Shaozhen, Zhou, Kanheng, Nabi, Ghulam, Huang, Zhihong, Ben-Ezra, Shmuel, Rosen, Shani, Mihcin, Senay, Strehlow, Jan, Karakitsios, Ioannis, Le, Nhan, Schwenke, Michael, Demedts, Daniel, Prentice, Paul, Haase, Sabrina, Preusser, Tobias, Melzer, Andreas, Mestas, Jean-Louis, Chettab, Kamel, Gomez, Gustavo Stadthagen, Dumontet, Charles, Werle, Bettina, Marquet, Fabrice, Bour, Pierre, Vaillant, Fanny, Amraoui, Sana, Dubois, Rémi, Ritter, Philippe, Haïssaguerre, Michel, Hocini, Mélèze, Bernus, Olivier, Quesson, Bruno, Livneh, Amit, Adam, Dan, Robin, Justine, Arnal, Bastien, Fink, Mathias, Pernot, Mathieu, Khokhlova, Tatiana D., Schade, George R., Wang, Yak-Nam, Kreider, Wayne, Simon, Julianna, Starr, Frank, Karzova, Maria, Maxwell, Adam, Bailey, Michael R., Lundt, Jonathan E., Allen, Steven P., Sukovich, Jonathan R., Hall, Timothy, Xu, Zhen, May, Philip, Lin, Daniel W., Constans, Charlotte, Deffieux, Thomas, Aubry, Jean-Francois, Park, Eun-Joo, Ahn, Yun Deok, Kang, Soo Yeon, Park, Dong-Hyuk, Lee, Jae Young, Vidal-Jove, J., Perich, E., Ruiz, A., Jaen, A., Eres, N., del Castillo, M. Alvarez, Myers, Rachel, Kwan, James, Coviello, Christian, Rowe, Cliff, Crake, Calum, Finn, Sean, Jackson, Edward, Pouliopoulos, Antonios, Li, Caiqin, Tinguely, Marc, Tang, Meng-Xing, Garbin, Valeria, Choi, James J., Folkes, Lisa, Stratford, Michael, Nwokeoha, Sandra, Li, Tong, Farr, Navid, D’Andrea, Samantha, Gravelle, Kayla, Chen, Hong, Lee, Donghoon, Hwang, Joo Ha, Tardoski, Sophie, Ngo, Jacqueline, Gineyts, Evelyne, Roux, Jean-Pau, Clézardin, Philippe, Conti, Allegra, Magnin, Rémi, Gerstenmayer, Matthieu, Lux, François, Tillement, Olivier, Mériaux, Sébastien, Penna, Stefania Della, Romani, Gian Luca, Dumont, Erik, Sun, Tao, Power, Chanikarn, Miller, Eric, Sapozhnikov, Oleg, Tsysar, Sergey, Yuldashev, Petr V., Svet, Victor, Li, Dongli, Pellegrino, Antonio, Petrinic, Nik, Siviour, Clive, Jerusalem, Antoine, Yuldashev, Peter V., Cunitz, Bryan W., Dunmire, Barbrina, Inserra, Claude, Guedra, Matthieu, Mauger, Cyril, Gilles, Bruno, Solovchuk, Maxim, Sheu, Tony W. H., Thiriet, Marc, Zhou, Yufeng, Neufeld, Esra, Baumgartner, Christian, Payne, Davnah, Kyriakou, Adamos, Kuster, Niels, Xiao, Xu, McLeod, Helen, Dillon, Christopher, Payne, Allison, Khokhova, Vera A., Sinilshchikov, Ilya, Andriyakhina, Yulia, Rybyanets, Andrey, Shvetsova, Natalia, Berkovich, Alex, Shvetsov, Igor, Shaw, Caroline J., Civale, John, Giussani, Dino, Lees, Christoph, Ozenne, Valery, Toupin, Solenn, Salgaonkar, Vasant, Kaye, Elena, Monette, Sebastien, Maybody, Majid, Srimathveeravalli, Govindarajan, Solomon, Stephen, Gulati, Amitabh, Bezzi, Mario, Jenne, Jürgen W., Lango, Thomas, Müller, Michael, Sat, Giora, Tanner, Christine, Zangos, Stephan, Günther, Matthias, Dinh, Au Hoang, Niaf, Emilie, Bratan, Flavie, Guillen, Nicolas, Souchon, Rémi, Lartizien, Carole, Crouzet, Sebastien, Rouviere, Olivier, Han, Yang, Payen, Thomas, Palermo, Carmine, Sastra, Steve, Olive, Kenneth, van Breugel, Johanna M., van den Bosch, Maurice A., Fellah, Benjamin, Le Bihan, Denis, Hernandez-Garcia, Luis, Cain, Charles A., Lyka, Erasmia, Elbes, Delphine, Li, Chunhui, Tamano, Satoshi, Jimbo, Hayato, Yoshizawa, Shin, Fujiwara, Keisuke, Itani, Kazunori, Umemura, Shin-ichiro, Stoianovici, Dan, Zaini, Zulfadhli, Takagi, Ryo, Zong, Shenyan, Watkins, Ron, Pascal-Tenorio, Aurea, Jones, Peter, Butts-Pauly, Kim, Bouley, Donna, Chen, Yazhu, Lin, Chung-Yin, Hsieh, Han-Yi, Wei, Kuo-Chen, Garnier, Camille, Renault, Gilles, Seifabadi, Reza, Wilson, Emmanuel, Eranki, Avinash, Kim, Peter, Lübke, Dennis, Huber, Peter, Georgii, Joachim, Dresky, Caroline V., Haller, Julian, Yarmolenko, Pavel, Sharma, Karun, Celik, Haydar, Li, Guofeng, Qiu, Weibao, Zheng, Hairong, Tsai, Meng-Yen, Chu, Po-Chun, Webb, Taylor, Vyas, Urvi, Walker, Matthew, Zhong, Jidan, Waspe, Adam C., Hodaie, Mojgan, Yang, Feng-Yi, Huang, Sin-Luo, Zur, Yuval, Assif, Benny, Aurup, Christian, Kamimura, Hermes, Carneiro, Antonio A., Rothlübbers, Sven, Schwaab, Julia, Houston, Graeme, Azhari, Haim, Weiss, Noam, Sosna, Jacob, Goldberg, S. Nahum, Barrere, Victor, Jang, Kee W., Lewis, Bobbi, Wang, Xiaotong, Suomi, Visa, Edwards, David, Larrabee, Zahary, Hananel, Arik, Rafaely, Boaz, Debbiny, Rasha Elaimy, Dekel, Carmel Zeltser, Assa, Michael, Menikou, George, Mouratidis, Petros, Pineda-Pardo, José A., de Pedro, Marta Del Álamo, Martinez, Raul, Hernandez, Frida, Casas, Silvia, Oliver, Carlos, Pastor, Patricia, Vela, Lidia, Obeso, Jose, Greillier, Paul, Zorgani, Ali, Catheline, Stefan, Solovov, Vyacheslav, Vozdvizhenskiy, Michael O., Orlov, Andrew E., Wu, Chueh-Hung, Sun, Ming-Kuan, Shih, Tiffany T., Chen, Wen-Shiang, Prieur, Fabrice, Pillon, Arnaud, Cartron, Valerie, Cebe, Patrick, Chansard, Nathalie, Lafond, Maxime, Seya, Pauline Muleki, Bera, Jean-Christophe, Boissenot, Tanguy, Fattal, Elias, Bordat, Alexandre, Chacun, Helene, Guetin, Claire, Tsapis, Nicolas, Maruyama, Kazuo, Unga, Johan, Suzuki, Ryo, Fant, Cécile, Rogez, Bernadette, Afadzi, Mercy, Myhre, Ola Finneng, Vea, Siri, Bjørkøy, Astrid, Yemane, Petros Tesfamichael, van Wamel, Annemieke, Berg, Sigrid, Hansen, Rune, Angelsen, Bjørn, and Davies, Catharina

Subjects
Meeting Abstracts
Published
2017

157. Melatonin modulates the fetal cardiovascular defense response to acute hypoxia

Author

Thakor, Avnesh S, Allison, Beth J, Niu, Youguo, Botting, Kimberley J, Serón-Ferré, Maria, Herrera, Emilio A, Giussani, Dino A, Giussani, Dino [0000-0002-1308-1204], and Apollo - University of Cambridge Repository

Subjects
Oxidative Stress, Catecholamines, Fetus, Sheep, Pregnancy, hypoxia, cardiovascular, Animals, Female, melatonin, Nitric Oxide
Abstract

Experimental studies in animal models supporting protective effects on the fetus of melatonin in adverse pregnancy have prompted clinical trials in human pregnancy complicated by fetal growth restriction. However, the effects of melatonin on the fetal defense to acute hypoxia, such as that which may occur during labor, remain unknown. This translational study tested the hypothesis, in vivo, that melatonin modulates the fetal cardiometabolic defense responses to acute hypoxia in chronically instrumented late gestation fetal sheep via alterations in fetal nitric oxide (NO) bioavailability. Under anesthesia, 6 fetal sheep at 0.85 gestation were instrumented with vascular catheters and a Transonic flow probe around a femoral artery. Five days later, fetuses were exposed to acute hypoxia with or without melatonin treatment. Fetal blood was taken to determine blood gas and metabolic status and plasma catecholamine concentrations. Hypoxia during melatonin treatment was repeated during in vivo NO blockade with the NO clamp. This technique permits blockade of de novo synthesis of NO while compensating for the tonic production of the gas, thereby maintaining basal cardiovascular function. Melatonin suppressed the redistribution of blood flow away from peripheral circulations and the glycemic and plasma catecholamine responses to acute hypoxia. These are important components of the fetal brain sparing response to acute hypoxia. The effects of melatonin involved NO-dependent mechanisms as the responses were reverted by fetal treatment with the NO clamp. Melatonin modulates the in vivo fetal cardiometabolic responses to acute hypoxia by increasing NO bioavailability.

Published
2015

160. Improving pregnancy outcomes in humans through studies in sheep

Author

Morrison, Janna L., primary, Berry, Mary J., additional, Botting, Kimberley J., additional, Darby, Jack R. T., additional, Frasch, Martin G., additional, Gatford, Kathryn L., additional, Giussani, Dino A., additional, Gray, Clint L., additional, Harding, Richard, additional, Herrera, Emilio A., additional, Kemp, Matthew W., additional, Lock, Mitchell C., additional, McMillen, I. Caroline, additional, Moss, Timothy J., additional, Musk, Gabrielle C., additional, Oliver, Mark H., additional, Regnault, Timothy R. H., additional, Roberts, Claire T., additional, Soo, Jia Yin, additional, and Tellam, Ross L., additional

Published
2018
Full Text
View/download PDF

162. Maternal diet-induced obesity programmes cardiac dysfunction in male mice independently of post-weaning diet

Author

Loche, Elena, primary, Blackmore, Heather L, additional, Carpenter, Asha A, additional, Beeson, Jessica H, additional, Pinnock, Adele, additional, Ashmore, Thomas J, additional, Aiken, Catherine E, additional, de Almeida-Faria, Juliana, additional, Schoonejans, Josca M, additional, Giussani, Dino A, additional, Fernandez-Twinn, Denise S, additional, and Ozanne, Susan E, additional

Published
2018
Full Text
View/download PDF

164. Developmental Expression and Glucocorticoid Control of the Leptin Receptor in Fetal Ovine Lung

Author

De Blasio, Miles J, Boije, Maria, Vaughan, Owen R, Bernstein, Brett S, Davies, Katie L, Plein, Alice, Kempster, Sarah L, Smith, Gordon CS, Charnock-Jones, D Stephen, Blache, Dominique, Wooding, FB Peter, Giussani, Dino A, Fowden, Abigail L, Forhead, Alison J, Smith, Gordon [0000-0003-2124-0997], Charnock-Jones, Stephen [0000-0002-2936-4890], Wooding, Peter [0000-0003-2471-7586], Giussani, Dino [0000-0002-1308-1204], Fowden, Abigail [0000-0002-3384-4467], Forhead, Alison [0000-0003-2125-4811], and Apollo - University of Cambridge Repository

Subjects
STAT3 Transcription Factor, Hydrocortisone, lcsh:R, Gene Expression Regulation, Developmental, lcsh:Medicine, respiratory system, Dexamethasone, Fetus, Pregnancy, Alveolar Epithelial Cells, Animals, Receptors, Leptin, Female, lcsh:Q, RNA, Messenger, Phosphorylation, lcsh:Science, Glucocorticoids, Lung, Sheep, Domestic, Research Article, Signal Transduction
Abstract

The effects of endogenous and synthetic glucocorticoids on fetal lung maturation are well-established, although the role of leptin in lung development before birth is unclear. This study examined mRNA and protein levels of the signalling long-form leptin receptor (Ob-Rb) in fetal ovine lungs towards term, and after experimental manipulation of glucocorticoid levels in utero by fetal cortisol infusion or maternal dexamethasone treatment. In fetal ovine lungs, Ob-Rb protein was localised to bronchiolar epithelium, bronchial cartilage, vascular endothelium, alveolar macrophages and type II pneumocytes. Pulmonary Ob-Rb mRNA abundance increased between 100 (0.69 fractional gestational age) and 144 days (0.99) of gestation, and by 2-4-fold in response to fetal cortisol infusion and maternal dexamethasone treatment. In contrast, pulmonary Ob-Rb protein levels decreased near term and were halved by glucocorticoid treatment, without any significant change in phosphorylated signal transducer and activator of transcription-3 (pSTAT3) at Ser727, total STAT3 or the pulmonary pSTAT3:STAT3 ratio. Leptin mRNA was undetectable in fetal ovine lungs at the gestational ages studied. These findings demonstrate differential control of pulmonary Ob-Rb transcript abundance and protein translation, and/or post-translational processing, by glucocorticoids in utero. Localisation of Ob-Rb in the fetal ovine lungs, including alveolar type II pneumocytes, suggests a role for leptin signalling in the control of lung growth and maturation before birth.

Published
2015

165. Maternal diet-induced obesity programmes cardiovascular dysfunction in adult male mouse offspring independent of current body weight

Author

Blackmore, Heather L, Niu, Youguo, Twinn, Denise, Tarry-Adkins, Jane L, Giussani, Dino, Ozanne, Susan, Twinn, Denise [0000-0003-2610-277X], Giussani, Dino [0000-0002-1308-1204], Ozanne, Susan [0000-0001-8753-5144], and Apollo - University of Cambridge Repository

Subjects
prenatal exposure delayed effects, cardiac hypertrophy, maternal diet
Abstract

Obese pregnancies are not only associated with adverse consequences for the mother but also the long-term health of her child. Human studies have shown that individuals from obese mothers are at increased risk of premature death from cardiovascular disease (CVD), but are not able to define causality. This study aimed to determine causality using a mouse model of maternal diet-induced obesity. Obesity was induced in female C57BL/6 mice by feeding a diet rich in simple sugars and saturated fat 6 weeks prior to pregnancy and throughout pregnancy and lactation. Control femaleswere fed laboratory chow. Male offspring from both groups were weaned onto chow and studied at 3, 5, 8 and 12 weeks of age for gross cardiac morphometry using stereology, cardiomyocyte cell area by histology and cardiac fetal gene expression using qRT-PCR. Cardiac function was assessed by isolated Langendorff technology at 12 weeks of age and hearts were analysed at the protein level for the expression of the β1 adrenergic receptor, muscarinic type-2 acetylcholine receptor and proteins involved in cardiac contraction. Offspring from obese mothers develop pathologic cardiac hypertrophy associated with re-expression of cardiac fetal genes. By young adulthood these offspring developed severe systolic and diastolic dysfunction and cardiac sympathetic dominance. Importantly, cardiac dysfunction occurred in the absence of any change in corresponding body weight and despite the offspring eating a healthy low fat diet. These findings provide a causal link to explain human observations relating maternal obesity with premature death from CVD in her offspring.

Published
2014

167. Cardiovascular function in term fetal sheep conceived, gestated and studied in the hypobaric hypoxia of the andean altiplano

Author

Herrera, Emilio A, Rojas, Rodrigo T, Krause, Bernardo J, Ebensperger, German, Reyes, Roberto V, Giussani, Dino A, Parer, Julian T, and Llanos, Anibal J

Abstract

High-altitude hypoxia causes intrauterine growth restriction and cardiovascular programming. However, adult humans and animals that have evolved at altitude show certain protection against the effects of chronic hypoxia. Whether the highland fetus shows s

Published
2016

169. Maternal chronic hypoxia increases expression of genes regulating lung liquid movement and surfactant maturation in male fetuses in late gestation

Author

McGillick, Erin V., primary, Orgeig, Sandra, additional, Allison, Beth J., additional, Brain, Kirsty L., additional, Niu, Youguo, additional, Itani, Nozomi, additional, Skeffington, Katie L., additional, Kane, Andrew D., additional, Herrera, Emilio A., additional, Giussani, Dino A., additional, and Morrison, Janna L., additional

Published
2017
Full Text
View/download PDF

171. Purinergic contribution to circulatory, metabolic, and adrenergic responses to acute hypoxemia in fetal sheep

Author

GIUSSANI, DINO A., GARDNER, DAVID S., COX, DAVID T., and FLETCHER, ANDREW J. W.

Subjects
Hypoxia -- Physiological aspects, Adrenergic mechanisms -- Research, Adenosine -- Physiological aspects, Sheep -- Physiological aspects, Biological sciences
Abstract

This study investigated the effects on femoral vascular resistance, blood glucose and lactate levels, and plasma catecholamine concentrations of fetal treatment with an adenosine receptor antagonist during acute hypoxemia in fetal sheep during late gestation. Under anesthesia, seven fetal sheep were instrumented between 117 and 118 days gestation (term is ~145 days) with vascular and amniotic catheters and an ultrasonic probe around a femoral artery. Six days after surgery, all fetuses were randomly subjected to a 3-h experiment consisting of 1 h of normoxia, 1 h of hypoxemia, and 1 h of recovery. This was done during either intravenous infusion of vehicle or the adenosine receptor antagonist [8-(p-sulfophenyl)-the-ophylline; 8-SPT] dissolved in vehicle. During vehicle infusion, all fetuses responded to hypoxemia with bradycardia, an increase in arterial blood pressure, and femoral vasoconstriction. Increases in blood glucose and lactate concentrations and in plasma epinephrine and norepinephrine concentrations also occurred in all fetuses during hypoxemia. Fetal treatment with 8-SPT markedly attenuated the bradycardic, hypertensive, vasoconstrictor, glycemic, and adrenergic responses to hypoxemia, but it did not affect the increase in blood lactate concentrations during hypoxemia. These data show that adenosine is involved in the mechanisms mediating fetal cardiovascular, metabolic, and adrenergic responses to hypoxemia in fetal sheep. Fetal treatment with 8-SPT mimics the effects of carotid sinus nerve section on fetal cardiovascular function during hypoxemia, suggesting a role for adenosine in mediating fetal cardiovascular chemoreflexes. fetus; cardiovascular; hypoxia; chemoreflex

Published
2001

173. Phase-rectified signal averaging method to predict perinatal outcome in infants with very preterm fetal growth restriction- a secondary analysis of TRUFFLE-trial

Author

Lobmaier, Silvia M., Mensing van Charante, Nico, Ferrazzi, Enrico, Giussani, Dino A., Shaw, Caroline J., Müller, Alexander, Ortiz, Javier U., Ostermayer, Eva, Haller, Bernhard, Prefumo, Federico, Frusca, Tiziana, Hecher, Kurt, Arabin, Birgit, Thilaganathan, Baskaran, Papageorghiou, Aris T., Bhide, Amarnath, Martinelli, Pasquale, Duvekot, Johannes J., van Eyck, Jim, Visser, Gerard H A, Schmidt, Georg, Ganzevoort, Wessel, Lees, Christoph C., Schneider, Karl T M, Bilardo, Caterina M., Brezinka, Christoph, Diemert, Anke, Derks, Jan B., Schlembach, Dietmar, Todros, Tullia, Valcamonico, Adriana, Marlow, Neil, van Wassenaer-Leemhuis, Aleid, Lobmaier, Silvia M., Mensing van Charante, Nico, Ferrazzi, Enrico, Giussani, Dino A., Shaw, Caroline J., Müller, Alexander, Ortiz, Javier U., Ostermayer, Eva, Haller, Bernhard, Prefumo, Federico, Frusca, Tiziana, Hecher, Kurt, Arabin, Birgit, Thilaganathan, Baskaran, Papageorghiou, Aris T., Bhide, Amarnath, Martinelli, Pasquale, Duvekot, Johannes J., van Eyck, Jim, Visser, Gerard H A, Schmidt, Georg, Ganzevoort, Wessel, Lees, Christoph C., Schneider, Karl T M, Bilardo, Caterina M., Brezinka, Christoph, Diemert, Anke, Derks, Jan B., Schlembach, Dietmar, Todros, Tullia, Valcamonico, Adriana, Marlow, Neil, and van Wassenaer-Leemhuis, Aleid

Published
2016

174. Phase-rectified signal averaging method to predict perinatal outcome in infants with very preterm fetal growth restriction- a secondary analysis of TRUFFLE-trial

Author

MS Verloskunde, Other research (not in main researchprogram), Lobmaier, Silvia M., Mensing van Charante, Nico, Ferrazzi, Enrico, Giussani, Dino A., Shaw, Caroline J., Müller, Alexander, Ortiz, Javier U., Ostermayer, Eva, Haller, Bernhard, Prefumo, Federico, Frusca, Tiziana, Hecher, Kurt, Arabin, Birgit, Thilaganathan, Baskaran, Papageorghiou, Aris T., Bhide, Amarnath, Martinelli, Pasquale, Duvekot, Johannes J., van Eyck, Jim, Visser, Gerard H A, Schmidt, Georg, Ganzevoort, Wessel, Lees, Christoph C., Schneider, Karl T M, Bilardo, Caterina M., Brezinka, Christoph, Diemert, Anke, Derks, Jan B., Schlembach, Dietmar, Todros, Tullia, Valcamonico, Adriana, Marlow, Neil, van Wassenaer-Leemhuis, Aleid, MS Verloskunde, Other research (not in main researchprogram), Lobmaier, Silvia M., Mensing van Charante, Nico, Ferrazzi, Enrico, Giussani, Dino A., Shaw, Caroline J., Müller, Alexander, Ortiz, Javier U., Ostermayer, Eva, Haller, Bernhard, Prefumo, Federico, Frusca, Tiziana, Hecher, Kurt, Arabin, Birgit, Thilaganathan, Baskaran, Papageorghiou, Aris T., Bhide, Amarnath, Martinelli, Pasquale, Duvekot, Johannes J., van Eyck, Jim, Visser, Gerard H A, Schmidt, Georg, Ganzevoort, Wessel, Lees, Christoph C., Schneider, Karl T M, Bilardo, Caterina M., Brezinka, Christoph, Diemert, Anke, Derks, Jan B., Schlembach, Dietmar, Todros, Tullia, Valcamonico, Adriana, Marlow, Neil, and van Wassenaer-Leemhuis, Aleid

Published
2016

176. Phase-rectified signal averaging method to predict perinatal outcome in infants with very preterm fetal growth restriction- a secondary analysis of TRUFFLE-trial

Author

Lobmaier, Silvia M., primary, Mensing van Charante, Nico, additional, Ferrazzi, Enrico, additional, Giussani, Dino A., additional, Shaw, Caroline J., additional, Müller, Alexander, additional, Ortiz, Javier U., additional, Ostermayer, Eva, additional, Haller, Bernhard, additional, Prefumo, Federico, additional, Frusca, Tiziana, additional, Hecher, Kurt, additional, Arabin, Birgit, additional, Thilaganathan, Baskaran, additional, Papageorghiou, Aris T., additional, Bhide, Amarnath, additional, Martinelli, Pasquale, additional, Duvekot, Johannes J., additional, van Eyck, Jim, additional, Visser, Gerard H.A., additional, Schmidt, Georg, additional, Ganzevoort, Wessel, additional, Lees, Christoph C., additional, Schneider, Karl T.M., additional, Bilardo, Caterina M., additional, Brezinka, Christoph, additional, Diemert, Anke, additional, Derks, Jan B., additional, Schlembach, Dietmar, additional, Todros, Tullia, additional, Valcamonico, Adriana, additional, Marlow, Neil, additional, and van Wassenaer-Leemhuis, Aleid, additional

Published
2016
Full Text
View/download PDF

179. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease

Author

Allison, Beth J., primary, Kaandorp, Joepe J., additional, Kane, Andrew D., additional, Camm, Emily J., additional, Lusby, Ciara, additional, Cross, Christine M., additional, Nevin‐Dolan, Rhianon, additional, Thakor, Avnesh S., additional, Derks, Jan B., additional, Tarry‐Adkins, Jane L., additional, Ozanne, Susan E., additional, and Giussani, Dino A., additional

Published
2016
Full Text
View/download PDF

185. Sildenafil therapy for fetal cardiovascular dysfunction during hypoxic development: studies in the chick embryo.

Author

Itani, Nozomi, Skeffington, Katie L., Beck, Christian, and Giussani, Dino A.

Subjects
CARDIOVASCULAR disease diagnosis, SILDENAFIL, PLACENTA abnormalities, FETAL development, CHICKEN embryos, PREVENTION, DIAGNOSIS, THERAPEUTICS
Abstract

Key points Common complications of pregnancy, such as chronic fetal hypoxia, trigger a fetal origin of cardiovascular dysfunction and programme cardiovascular disease in later life., Sildenafil treatment protects placental perfusion and fetal growth, but whether the effects of sildenafil transcend the placenta to affect the fetus is unknown., Using the chick embryo model, here we show that sildenafil treatment directly protects the fetal cardiovascular system in hypoxic development, and that the mechanisms of sildenafil protection include reduced oxidative stress and increased nitric oxide bioavailability;, Sildenafil does not protect against fetal growth restriction in the chick embryo, supporting the idea that the protective effect of sildenafil on fetal growth reported in mammalian studies, including humans, is secondary to improved placental perfusion., Therefore, sildenafil may be a good candidate for human translational antioxidant therapy to protect the chronically hypoxic fetus in adverse pregnancy., Abstract There is a need for developing clinically translatable therapy for preventing fetal origins of cardiovascular disease in pregnancy complicated by chronic fetal hypoxia. Evidence shows that sildenafil protects placental perfusion and fetal growth. However, whether beneficial effects of sildenafil transcend onto the fetal heart and circulation in complicated development is unknown. We isolated the direct effects of sildenafil on the fetus using the chick embryo and hypothesised that sildenafil also protects fetal cardiovascular function in hypoxic development. Chick embryos ( n = 11 per group) were incubated in normoxia or hypoxia (14% O2) from day 1 and treated with sildenafil (4 mg kg−1 day−1) from day 13 of the 21-day incubation. Hypoxic incubation increased oxidative stress (4-hydroxynonenal, 141.1 ± 17.6% of normoxic control), reduced superoxide dismutase (60.7 ± 6.3%), increased phosphodiesterase type 5 expression (167 ± 13.7%) and decreased nitric oxide bioavailability (54.7 ± 6.1%) in the fetal heart, and promoted peripheral endothelial dysfunction (70.9 ± 5.6% AUC of normoxic control; all P < 0.05). Sildenafil treatment after onset of chronic hypoxia prevented the increase in phosphodiesterase expression (72.5 ± 22.4%), protected against oxidative stress (94.7 ± 6.2%) and normalised nitric oxide bioavailability (115.6 ± 22.3%) in the fetal heart, and restored endothelial function in the peripheral circulation (89.8 ± 2.9%). Sildenafil protects the fetal heart and circulation directly in hypoxic development via mechanisms including decreased oxidative stress and enhanced nitric oxide bioavailability. Sildenafil may be a good translational candidate for human antioxidant therapy to prevent fetal origins of cardiovascular dysfunction in adverse pregnancy. [ABSTRACT FROM AUTHOR]

Published
2017
Full Text
View/download PDF

187. Contributors

Author

Abbasi, Soraya, Abbey, James, Adzick, N. Scott, Ahn, Sun-Young, Albertine, Kurt H., Allegaert, Karel, Alper, Seth L., Altit, Gabriel, Altschuler, Steven M., Alvaro, Ruben E., Amorosa, Jennifer M.H., Anbuhl, Kelsey L., Andersen, Claus Yding, Anderson, Richard A., Askenazi, David J., Auten, Richard Lambert, Jr., Autmizguine, Julie, Azhibekov, Timur, Back, Stephen A., Badaut, Jérôme, Baker, Peter Russell, II, Ballard, Philip L., Bancalari, Eduardo H., Barichello, Tatiana, Battaglia, Frederick, Baum, Michel, Beggs, Simon, Bell, Edward F., Benchimol, Corinne, Benders, Manon J.N.L., Bennet, Laura, Bennett, Phillip R., Berger, Melvin, Bernhard, Wolfgang, Bertram, John F., Bhosle, Vikrant K., Bhutani, Vinod K., Black, M. Jane, Bliss, Joseph M., Bolender, David L., Brandenburg, Joline E., Broussard, Delma L., Brown, Laura Davidson, Burrin, Douglas G., Cannon, Barbara, Caplan, Michael, Carlson, Susan E., Carlton, David P., Caruana, Georgina, Cashore, William J., Chaemsaithong, Piya, Chaiyasit, Noppadol, Charlton, Jennifer R., Cheatham, Carol L., Chemtob, Sylvain, Chen, Yi-Yung, Chevalier, Robert L., Chheda, Sadhana, Childs, Andrew J., Christensen, Robert D., Chu, Alison, Chu, David H., Cilio, Maria Roberta, Clark, David A., Cleary-Goldman, Jane, Clemente, Ethel G., Clements, John A., Clyman, Ronald I., Cohen, Susan S., Colombo, John, Cowett, Richard M., Crawford, Peter A., Crowe, James E., Jr., Cullen-McEwen, Luise A., Cutfield, Wayne S., D'Alton, Mary E., Danzer, Enrico, Delacourt, Christophe, Devaskar, Sherin U., Diacovo, Thomas G., Docheva, Nikolina, Dormans, John P., Dysart, Kevin, El-Khuffash, Afif, Ellis, Peter James, Empey, Kerry McGarr, Ercal, Baris, Erdős, Melinda, Erickson, Robert P., Fahim, Mohamed A., Faksh, Arij, Frank, Hans-Georg, Friedlich, Philippe S., Friedman, Jed, Gao, Yuansheng, Garland, Marianne, Geddes, Donna, Georgieff, Michael K., Gien, Jason, Giussani, Dino A., Goldman, Armond S., González, Efrén, Good, Misty, Grant, Denis M., Green, Lucy R., Grigoriou, Emmanouil, Grimberg, Adda, Gross, Ian, Grunau, Ruth E., Guignard, Jean-Pierre, Gunn, Alistair Jan, Gurtunca, Nursen, Hadchouel, Alice, Haddad, Gabriel G., Hagberg, Henrik, Hale, Thomas, Hambidge, K. Michael, Hammerman, Cathy, Hansen, Thor Willy Ruud, Hanson, Mark A., Harding, Richard, Harris, Mary Catherine, Hartmann, Peter, Hassiotou, Foteini, Haugen, Guttorm, Hawkes, Colin P., Hay, William W., Jr., Hayward, Christina E., Heine, Vivi M., Hellström, Ann, Helmrath, Michael A., Hendricks-Muñoz, Karen D., Herrera, Emilio, Hiatt, Michael J., Hoath, Steven B., Hooper, Stuart B., Huang, Stephen A., Iacobellli, Silvia, Inder, Terrie E., Iruela-Arispe, M. Luisa, Jadcherla, Sudarshan R., Jain, Deepak, Jansson, Thomas, Jefferies, John Lynn, Jetton, Jennifer G., Jobe, Alan H., Johnson, Lois H., Johnston, Richard B., Jr., Jones, Rebecca Lee, Jose, Pedro A., Kalhan, Satish C., Kallapur, Suhas G., Kaplan, Michael, Kaplan, Stanley, Karpen, Heidi Eigenrauch, Karpen, Saul J., Karumanchi, S. Ananth, Kaskel, Frederick J., Katheria, Anup C., Katz, Lorraine E. Levitt, Keeney, Susan E., Kern, Steven E., Khanjani, Shirin, Kilpatrick, Laurie E., Kim, Chang-Ryul, Kinsella, John P., Kiserud, Torvid, Koenig, Joyce M., Kollmann, Tobias R., Kolls, Jay K., Krebs, Nancy F., Kulik, Thomas J., Kutikov, Jessica Katz, Lakshminrusimha, Satyan, Lamola, Angelo A., Lasunción, Miguel Angel, Lavoie, Pascal M., LeBien, Tucker W., Lee, Mary M., Lee, Matthew K., Lee, Yvonne K., Leibel, Sandra, Levine, Fred, Levy, Ofer, Liu, Yang, Lobritto, Steven, Loomis, Cynthia A., Lopez, Colleen A., MacIntyre, David A., Mahe, Maxime M., Maheshwari, Akhil, Mankouski, Anastasiya, Mantilla, Carlos B., Marchant, Arnaud, Margolis, Kara Gross, Mariscalco, M. Michele, Maródi, László, Maršál, Karel, Martin, Richard J., Matsell, Douglas G., Matthews, Dwight E., McArdle, Harry J., McManaman, James L., McNamara, Patrick J., McQuillen, Patrick S., McQuinn, Tim C., Mercer, Judith S., Meschia, Giacomo, Miller, Steven P., Minoo, Parviz, Monagle, Paul, Mortola, Jacopo P., Muglia, Louis J., Munshi, Upender K., Namgung, Ran, Narasimhan, Sumana, Nedergaard, Jan, Neu, Josef, Nigam, Sanjay K., Nogee, Lawrence M., Noori, Shahab, O'Brien, Barbara M., Ohls, Robin K., Ortega-Senovilla, Henar, O'Sullivan, Justin M., Owusu, Sarah A., Pal, Abhijeet, Panitch, Howard B., Penn, Anna A., Penn, Raymond B., Pernia, Cameron, Philipps, Anthony F., Picoraro, Joseph A., Pisani, Francesco, Pleasure, David, Pleasure, Jeanette R., Pleasure, Samuel J., Pomeroy, Scott L., Post, Martin, Prakash, Y.S., Prozialeck, Joshua D., Pysher, Theodore J., Quigley, Raymond, Rabinovitch, Marlene, Raffay, Thomas M., Raj, J. Usha, Ramsey, Haley, Rana, Sarosh, Randis, Tara Marie, Ranger, Manon, Ratner, Adam J., Regnault, Timothy R.H., Rigatto, Henrique, Rintoul, Natalie E., Romero, Roberto, Rose, James C., Rosenfeld, Charles R., Ross, A. Catharine, Rozycki, Henry J., Ryan, Thomas D., Sahni, Rakesh, Sajti, Eniko, Sarnat, Harvey B., Satlin, Lisa M., Saugstad, Ola Didrik, Schierding, William, Schmalstieg, Frank C., Schwartz, George J., Schwartz, Jeffrey, Segar, Jeffrey L., Selewski, David T., Seri, Istvan, Shaffer, Thomas H., Shah, Kara N., Shearer, Martin J., Shojaie, Sharareh, Shroyer, Noah F., Sibley, Colin P., Sieck, Gary C., Simmons, Rebecca A., Sivieri, Emidio M., Smith, Francine G., Smith, Lois E.H., Smyth, Ian M., Snarr, Brian S., Snyder, Evan Y., Sola-Visner, Martha, Solhaug, Michael J., Sperling, Mark A., Srinivasan, Lakshmi, Stahl, Andreas, Stanley, Charles A., Steinhorn, Robin H., Stonestreet, Barbara S., Strasburger, Janette F., Styne, Dennis M., Sussel, Lori, Tam, Emily W.Y., Tan, Libo, Thornton, Claire, Tollin, Daniel J., Tóth, Beáta, Towbin, Jeffrey A., Trocle, Ashley, Truog, William E., Tsang, Reginald C., Uhler, Kristin M., Van Den Anker, John N., van Goudoever, Johannes (Hans) B., Vannucci, Susan J., Vickers, Mark H., Virgintino, Daniela, Volpe, Joseph J., Vora, Neeta L., Vyas, Neha V., Wacker-Gussmann, Annette, Wallace, Megan J., Walsh, Brian H., Wang, Alice M., Warburton, David, Ward, Robert M., Watterberg, Kristi L., Werner, Lynne A., Wershil, Barry K., Wert, Susan E., Wessels, Andy, Whitsett, Jeffrey A., Wise, Michael, Wolf, Matthias T., Wolfson, Marla R., Wong, Hector R., Wynn, James L., Yeo, Lami, Yip, Stephen, Yoder, Bradley A, Yoder, Mervin C., Yoshimoto, Momoko, Yuskaitis, Christopher J., Zhou, Dan, and Zovein, Ann

Published
2017
Full Text
View/download PDF

188. Placental Adaptation to Early-Onset Hypoxic Pregnancy and Mitochondria-Targeted Antioxidant Therapy in a Rodent Model

Author

Nuzzo, Anna M., Camm, Emily J., Sferruzzi-Perri, Amanda N., Ashmore, Thomas J., Yung, Hong-wa, Cindrova-Davies, Tereza, Spiroski, Ana-Mishel, Sutherland, Megan R., Logan, Angela, Austin-Williams, Shani, Burton, Graham J., Rolfo, Alessandro, Todros, Tullia, Murphy, Michael P., and Giussani, Dino A.

Abstract

The placenta responds to adverse environmental conditions by adapting its capacity for substrate transfer to maintain fetal growth and development. Early-onset hypoxia effects on placental morphology and activation of the unfolded protein response (UPR) were determined using an established rat model in which fetal growth restriction is minimized. We further established whether maternal treatment with a mitochondria-targeted antioxidant (MitoQ) confers protection during hypoxic pregnancy. Wistar dams were exposed to normoxia (21% O2) or hypoxia (13% to 14% O2) from days 6 to 20 of pregnancy with and without MitoQ treatment (500 μmol/L in drinking water). On day 20, animals were euthanized and weighed, and the placentas from male fetuses were processed for stereology to assess morphology. UPR activation in additional cohorts of frozen placentas was determined with Western blot analysis. Neither hypoxic pregnancy nor MitoQ treatment affected fetal growth. Hypoxia increased placental volume and the fetal capillary surface area and induced mitochondrial stress as well as the UPR, as evidenced by glucose-regulated protein 78 and activating transcription factor (ATF) 4 protein up-regulation. MitoQ treatment in hypoxic pregnancy increased placental maternal blood space surface area and volume and prevented the activation of mitochondrial stress and the ATF4 pathway. The data suggest that mitochondria-targeted antioxidants may be beneficial in complicated pregnancy via mechanisms protecting against placental stress and enhancing placental perfusion.

Published
2018
Full Text
View/download PDF

200. Chronic hypoxaemia as a molecular regulator of fetal lung development: implications for risk of respiratory complications at birth.

Author

McGillick, Erin V., Orgeig, Sandra, Giussani, Dino A., and Morrison, Janna L.

Subjects
ANIMALS, BIOLOGICAL models, CELLULAR signal transduction, CHRONIC diseases, FETAL growth retardation, GENES, LUNGS, PREGNANCY complications, PULMONARY surfactant, QUESTIONNAIRES, RESPIRATORY distress syndrome, SHEEP, OXIDATIVE stress, PRENATAL exposure delayed effects
Abstract

Exposure to altered intrauterine conditions during pregnancy influences both fetal growth and organ development. Chronic fetal hypoxaemia is a common pregnancy complication associated with intrauterine growth restriction (IUGR) that may influence the risk of infants experiencing respiratory complications at birth. There are a variety of signalling pathways that contribute to normal fetal lung development at the molecular level. The specific molecular effects of chronic hypoxaemia associated with IUGR on lung development are likely to be dependent on the specific aetiology (maternal, placental and/or fetal factors) that can alter hormone concentrations, oxygen and nutrient transport to the fetus. This review discusses molecular pathways that may contribute to altered fetal lung maturation following exposure to chronic hypoxaemia. Importantly, these studies highlight that the heterogeneity in respiratory outcomes at birth in this obstetric subpopulation are likely determined by the timing, severity and duration of chronic hypoxaemia encountered by the fetus during pregnancy. [ABSTRACT FROM AUTHOR]

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results