230: antenatal maternal hypoxic stress: adaptations of the placental renin-angiotensin system

1
nancy hypercholesterolemia. Women attending for routine antenatal care were recruited at 5 different timepoints (12, 20, 28 and 36 weeks gestation and day 1 postnatal). RESULTS: The majority (95.0%) were Caucasian, with a median age of 30 years (range 17-46). Median BMI was 25 (range 18-38) and 36 were current smokers (16.4%). Seventy-one women (71/219; 32.4%) had one parent with hypercholesterolemia. Cholesterol levels were ele- vated in all trimesters of pregnancy, with mean values from the first trimester outside the adult normal range. HDL levels ranged from 0.9-2.7mmol/L throughout pregnancy. In contrast, LDL levels ranged from 1.3-6.1mmol/L, and were 3.0mmol/L in 127 women (57.8%). There was no significant difference in cholesterol levels between cur- rent or non-smokers and in those with a family history of hypercho- lesterolemia. CONCLUSIONS: Total and LDL cholesterol levels were significantly raised throughout pregnancy. Levels were above normal as early as the first trimester, even in this relatively young healthy population of pregnant women. The implications of this on fetus and mother are still undetermined and deserve further investigation. Gestational week 11-14 19-22 27-29 35-37 day 1 postnatal median time 124 200 280 361 .......................................................................................................................................................................................... number of samples 48 49 32 44 46 .......................................................................................................................................................................................... Range 3.8-6.7 4.0-8.5 5.3-10.7 4.5-9.2 3.3-8.5 .......................................................................................................................................................................................... Mean 5.1 5.9 6.8 6.9 5.9 .......................................................................................................................................................................................... std dev 0.8 0.9 1.3 1.2 1.3 .......................................................................................................................................................................................... 229 Fetal sex and intra-uterine growth pattern Nir Melamed 1 , Avi Ben-Haroush 2 , Israel Meizner 1 , Reuven Mashiach 1 , Marek Glezerman 1 , Yariv Yogev 1 1 Helen Schneider Hospital for Women, Petach Tikva, 2 Helen Schneider Hospital for Women, Sackler Faculty of Medicine, Tel Aviv University, Petach Tikva OBJECTIVE: To analyze intrauterine growth patterns for male and fe- male fetuses, and to develop sex-specific reference growth models for the individual biometric indices and their ratios. STUDY DESIGN: We used a comprehensive database of sonographic fetal weight estimations of an unselected population in a single tertiary center. The effect of fetal sex on the intra-uterine growth patterns was analyzed for BPD, HC, OFD, AC, FL, and their ratios, and sex-specific regression models for the mean values of these measurements at each gestational week were generated. Regression model were generated also for the SD of each of these measurements as a function of gesta- tional age using the absolute residuals algorithm. RESULTS: 1) The study included 12,132 sonographic fetal weight esti- mations. 2) Intra-uterine growth patterns were significantly different between male and female fetuses for each of the five biometric indices (femalesmales, P0.001). These differences were most pronounced for BPD, and only minimal for femur length. 3) Significant sex-related differences were also found for all of the six ratio studies (P0.001), which were most pronounced for HC/FL and BPD/FL, and lowest for HC/AC, BPD/AC, and cephalic index. 4) For the head measurements, these differences were observed already at early second trimester and were highest at late third trimester. CONCLUSIONS: Female fetuses grow significantly slower than male fe- tuses, and these differenced are observed from early gestation. How- ever, these sex-related differences are not limited to a uniform slower growth of female fetuses. Instead, we found sex-specific growth pat- terns for each of the individual fetal biometric indices, as manifested by the sex-related differences in the ratios of biometric indices. These findings support the use of sex-specific sonographic models for fetal weight estimation as well as of sex-specific reference growth charts for each of the individual biometric indices and their ratios for the opti- mal interpretation of the sonographic findings. 230 Antenatal maternal hypoxic stress: adaptations of the placental renin-angiotensin system Rolanda Lister 1 , Ravi Goyal 1 , James Kurtzman 1 , Ciprian Gheorghe 1 , Bryan T. Oshiro 1 , Lawrence D. Longo 1 1 Loma Linda University School of Medicine, Loma Linda, CA OBJECTIVE: Antenatal Maternal Hypoxia (AMH) can result in patho- physiologic changes in both mother and fetus including alterations in placental morphology and gene regulation. We previously reported alterations in placental renin-angiotensin system (RAS) genes in a small animal model of placental insufficiency. The objective of this study was to test the hypothesis that antenatal maternal hypoxic stress in pregnant mice leads to alterations in the placental RAS similar to those observed with placental insufficiency. STUDY DESIGN: Pregnant FVB/NJ mice dams were exposed to 10.5% O 2 for 48 hours, from 15.5 to 17.5 day post coitum (n5) and com- pared to controls (n5). mRNA and protein expression of several RAS genes in the placenta were measured. p 0.05 was considered significant. RESULTS: 1) Placental angiotensinogen (AGT) mRNA was undetect- able in both groups; however, AGT protein expression was present and increased significantly with AMH compared to controls. 2) In AMH, although Renin mRNA levels were reduced, protein expression was increased in association with increased miRNA 199b, (yielding increased renin translation). 3) In AMH, placental angiotensin con- verting enzyme (ACE)-1 mRNA was unaltered; however, protein ex- pression increased significantly, in association with decreased miRNA 27a (yielding increased ACE-1 translation). 4) In AMH placenta, ACE-2 mRNA was significantly reduced, whereas protein expression was significantly greater, in association with reduced miRNA 429. 5) In AMH placenta, angiotensin II type (AT)-1a receptor mRNA ex- pression was unaltered and AT-1a receptor protein expression was unchanged; AT-2 receptor mRNA and proteins were undetectable in both groups. CONCLUSIONS: In the normal murine placenta, several components of RAS are present, and in response to AMH, several of these elements undergo important changes. In addition, differential expression of RAS mRNA and proteins indicate post-transcriptional regulatory mechanisms involved with hypoxic stress and warrant further inves- tigation. 231 Maternal lipopolysaccharide (LPS) alters the newborn oxidative stress and CRP levels in response to stress Yuval Ginsberg 1 , Nizar Khativ 1 , Nibal Awad 1 , Zeev Weiner 1 , Joseph Itskovitz-Eldor 1 , Michael Ross 2 , Ron Beloosesky 2 1 Rambam Med. Ctr., Haifa, 2 LABioMed at Harbor-UCLA Med. Ctr., Torrance, CA OBJECTIVE: Prenatal events are important determinants for disorders later in life. We have shown previously that acute maternal exposure to LPS at 18 days of gestation alters the offspring immune response and significantly decreases neonatal cytokine responses to LPS. As the immune response is mediated by oxidative stress we sought to deter- mine if offspring oxidative state and C-reactive protein (CRP) is pro- grammed by maternal inflammation exposure. STUDY DESIGN: Pregnant Sprague Dawley rats (n4) at 18 days’ ges- tation received intraperitoneal injections of saline (S) or LPS (500 g/kg). Male and female pups were delivered spontaneously (e21) and allowed to mature until postnatal day 24 (p24) when they received i.p. injection of LPS (100 g/kg). Serum lipid peroxidase formation (PD) and C-reactive protein (CRP) levels where determined prior to and at 4 hours after the LPS injection. RESULTS: At baseline, newborns of LPS treated dams had significantly higher oxidative stress (PD 344vs 104.9 nmol/ml) than control pups. In response to LPS, although no difference in PD, offspring of LPS treated dams had 3 fold greater CRP levels (20.42.8 vs 5.71.0 ng/ml; p 0.01). The formation of PD in response to AAPH (free radical generator) increased by 115 times in the S0 group compared www.AJOG.org Clinical Obstetrics, Neonatology, Physiology-Endocrinology Poster Session I Supplement to JANUARY 2011 American Journal of Obstetrics & Gynecology S99

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Page 1: 230: Antenatal maternal hypoxic stress: adaptations of the placental renin-angiotensin system

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www.AJOG.org Clinical Obstetrics, Neonatology, Physiology-Endocrinology Poster Session I

nancy hypercholesterolemia. Women attending for routine antenatalcare were recruited at 5 different timepoints (12, 20, 28 and 36 weeksgestation and day 1 postnatal).RESULTS: The majority (95.0%) were Caucasian, with a median age of

0 years (range 17-46). Median BMI was 25 (range 18-38) and 36 wereurrent smokers (16.4%). Seventy-one women (71/219; 32.4%) hadne parent with hypercholesterolemia. Cholesterol levels were ele-ated in all trimesters of pregnancy, with mean values from the firstrimester outside the adult normal range. HDL levels ranged from.9-2.7mmol/L throughout pregnancy. In contrast, LDL levels rangedrom 1.3-6.1mmol/L, and were �3.0mmol/L in 127 women (57.8%).here was no significant difference in cholesterol levels between cur-

ent or non-smokers and in those with a family history of hypercho-esterolemia.

CONCLUSIONS: Total and LDL cholesterol levels were significantlyaised throughout pregnancy. Levels were above normal as early as therst trimester, even in this relatively young healthy population ofregnant women. The implications of this on fetus and mother aretill undetermined and deserve further investigation.

Gestational week 11-14 19-22 27-29 35-37day 1postnatal

median time 12�4 20�0 28�0 36�1..........................................................................................................................................................................................

number of samples 48 49 32 44 46..........................................................................................................................................................................................

Range 3.8-6.7 4.0-8.5 5.3-10.7 4.5-9.2 3.3-8.5..........................................................................................................................................................................................

Mean 5.1 5.9 6.8 6.9 5.9..........................................................................................................................................................................................

std dev 0.8 0.9 1.3 1.2 1.3..........................................................................................................................................................................................

229 Fetal sex and intra-uterine growth patternNir Melamed1, Avi Ben-Haroush2, Israel Meizner1,

euven Mashiach1, Marek Glezerman1, Yariv Yogev1

1Helen Schneider Hospital for Women, Petach Tikva,2Helen Schneider Hospital for Women, Sackler Faculty

f Medicine, Tel Aviv University, Petach TikvaOBJECTIVE: To analyze intrauterine growth patterns for male and fe-

ale fetuses, and to develop sex-specific reference growth models forhe individual biometric indices and their ratios.

STUDY DESIGN: We used a comprehensive database of sonographicfetal weight estimations of an unselected population in a single tertiarycenter. The effect of fetal sex on the intra-uterine growth patterns wasanalyzed for BPD, HC, OFD, AC, FL, and their ratios, and sex-specificregression models for the mean values of these measurements at eachgestational week were generated. Regression model were generatedalso for the SD of each of these measurements as a function of gesta-tional age using the absolute residuals algorithm.RESULTS: 1) The study included 12,132 sonographic fetal weight esti-

ations. 2) Intra-uterine growth patterns were significantly differentetween male and female fetuses for each of the five biometric indicesfemales�males, P�0.001). These differences were most pronouncedor BPD, and only minimal for femur length. 3) Significant sex-relatedifferences were also found for all of the six ratio studies (P�0.001),hich were most pronounced for HC/FL and BPD/FL, and lowest forC/AC, BPD/AC, and cephalic index. 4) For the head measurements,

hese differences were observed already at early second trimester andere highest at late third trimester.

CONCLUSIONS: Female fetuses grow significantly slower than male fe-uses, and these differenced are observed from early gestation. How-ver, these sex-related differences are not limited to a uniform slowerrowth of female fetuses. Instead, we found sex-specific growth pat-erns for each of the individual fetal biometric indices, as manifestedy the sex-related differences in the ratios of biometric indices. Thesendings support the use of sex-specific sonographic models for fetaleight estimation as well as of sex-specific reference growth charts for

ach of the individual biometric indices and their ratios for the opti-

al interpretation of the sonographic findings. r

Supplem

230 Antenatal maternal hypoxic stress: adaptationsf the placental renin-angiotensin system

Rolanda Lister1, Ravi Goyal1, James Kurtzman1, Ciprianheorghe1, Bryan T. Oshiro1, Lawrence D. Longo1

1Loma Linda University School of Medicine, Loma Linda, CAOBJECTIVE: Antenatal Maternal Hypoxia (AMH) can result in patho-

hysiologic changes in both mother and fetus including alterations inlacental morphology and gene regulation. We previously reportedlterations in placental renin-angiotensin system (RAS) genes in amall animal model of placental insufficiency. The objective of thistudy was to test the hypothesis that antenatal maternal hypoxic stressn pregnant mice leads to alterations in the placental RAS similar tohose observed with placental insufficiency.

STUDY DESIGN: Pregnant FVB/NJ mice dams were exposed to 10.5%

2 for 48 hours, from 15.5 to 17.5 day post coitum (n�5) and com-ared to controls (n�5). mRNA and protein expression of severalAS genes in the placenta were measured. p � 0.05 was considered

ignificant.RESULTS: 1) Placental angiotensinogen (AGT) mRNA was undetect-ble in both groups; however, AGT protein expression was presentnd increased significantly with AMH compared to controls. 2) InMH, although Renin mRNA levels were reduced, protein expressionas increased in association with increased miRNA 199b, (yielding

ncreased renin translation). 3) In AMH, placental angiotensin con-erting enzyme (ACE)-1 mRNA was unaltered; however, protein ex-ression increased significantly, in association with decreased miRNA7a (yielding increased ACE-1 translation). 4) In AMH placenta,CE-2 mRNA was significantly reduced, whereas protein expressionas significantly greater, in association with reduced miRNA 429. 5)

n AMH placenta, angiotensin II type (AT)-1a receptor mRNA ex-ression was unaltered and AT-1a receptor protein expression wasnchanged; AT-2 receptor mRNA and proteins were undetectable inoth groups.

CONCLUSIONS: In the normal murine placenta, several components ofAS are present, and in response to AMH, several of these elementsndergo important changes. In addition, differential expression ofAS mRNA and proteins indicate post-transcriptional regulatoryechanisms involved with hypoxic stress and warrant further inves-

igation.

231 Maternal lipopolysaccharide (LPS) alters the newbornxidative stress and CRP levels in response to stress

Yuval Ginsberg1, Nizar Khativ1, Nibal Awad1, Zeev Weiner1,oseph Itskovitz-Eldor1, Michael Ross2, Ron Beloosesky2

1Rambam Med. Ctr., Haifa, 2LABioMedt Harbor-UCLA Med. Ctr., Torrance, CA

OBJECTIVE: Prenatal events are important determinants for disordersater in life. We have shown previously that acute maternal exposureo LPS at 18 days of gestation alters the offspring immune responsend significantly decreases neonatal cytokine responses to LPS. As themmune response is mediated by oxidative stress we sought to deter-

ine if offspring oxidative state and C-reactive protein (CRP) is pro-rammed by maternal inflammation exposure.

STUDY DESIGN: Pregnant Sprague Dawley rats (n�4) at 18 days’ ges-ation received intraperitoneal injections of saline (S) or LPS (500

g/kg). Male and female pups were delivered spontaneously (e21)nd allowed to mature until postnatal day 24 (p24) when they received.p. injection of LPS (100 □g/kg). Serum lipid peroxidase formationPD) and C-reactive protein (CRP) levels where determined prior to

and at 4 hours after the LPS injection.RESULTS: At baseline, newborns of LPS treated dams had significantly

igher oxidative stress (PD 34�4vs 10�4.9 nmol/ml) than controlups. In response to LPS, although no difference in PD, offspring ofPS treated dams had 3 fold greater CRP levels (20.4�2.8 vs 5.7�1.0g/ml; p� 0.01). The formation of PD in response to AAPH (free

adical generator) increased by 115 times in the S0 group compared

ent to JANUARY 2011 American Journal of Obstetrics & Gynecology S99