687: Altered estrogenic responsiveness in the adult mouse transcriptome following neonatal exposure...
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Saturday, February 8, 2014 d 10:00 am e 12:00 pm d Hilton Exhibition Center PREMATURITY, PHYSIOLOGY Abstracts 687 e 836 687 Altered estrogenic responsiveness in the adult mouse transcriptome following neonatal exposure to 17a-hydroxyprogesterone caproate Satomi Kohno 1 , Tomomi Sato 2 , Shinichi Miyagawa 3 , Roger Newman 1 , Taisen Iguchi 3 , Louis Guillette 1 1 Medical University of South Carolina, Obstetrics and Gynaecology, Charleston, SC, 2 Yokohama City University, Graduate School of Nanobioscience, Yokohama, Japan, 3 National Institute for Basic Biology, Okazaki Institute for Integrative Bioscience, Okazaki, Japan OBJECTIVE: The FDA has approved 17a-hydroxyprogesterone cap- roate (17PC), for the prevention of recurrent preterm birth. How- ever, the developmental effects of 17PC on reproductive health have not been fully explored. Altering the steroid hormone milieu during fetal development has potential long-term adverse consequences as observed with diethylstilbestrol exposure in utero. Our objective was to determine if developmental exposure to 17PC induces post-pu- bertal alterations to the female reproductive system. STUDY DESIGN: Neonatal mice (C57BL/6J) were given 5 daily in- jections SC (day 1-5) of 5 mg or 50 mg 17PC or a vehicle control (sesame oil), and were ovariectomized (OVX) at 8 wks as adults. Ten-days after OVX, 17b-estradiol (E 2 ) or a vehicle control (sesame oil) was injected IP at 5 mg/kg Body Weight. Six-hours after E 2 in- jection, mice were necropsied. Uterus, vagina, mammary gland, liver, hypothalamus and pituitary were isolated. Their transcriptomes were analyzed by microarray analysis. RESULTS: E 2 -stimulated uterine mass increased in all treatment groups as compared with adult control treatment (P<0.01). How- ever, the response to E 2 at the transcriptome level was different among the various neonatal treatments. E 2 remarkably altered the uterine transcriptome (826 genes went up; 1085 down) in controls, whereas significantly fewer genes were altered by E 2 in the uterus of mice neonatally exposed to 5 mg 17PC: 895 up/660 down or to 50 mg 17PC: 2 up/3 down. Altered sensitivity to E 2 was also observed in vagina, liver, mammary gland and pituitary, based on transcriptome data. CONCLUSION: Neonatal exposure to 17PC reduced the sensitivity to E 2 in multiple tissues of the adult mouse. Neonatal mice are equivalent to the 2nd trimester human fetus in terms of Müllerian duct development; thus, gestational treatment with 17PC between 16 and 36 weeks may result in offspring who exhibit altered estrogen sensitivity and reproductive function. This possibility demands further research. Estrogenic responsiveness in transcriptom was altered by neonatal exposure to 17a-hydroxyprogesterone caproate. Data were shown relative mRNA levels to control control group. 688 Atopobium vaginae reduces interval to delivery in high risk pregnancies Florence Bretelle 1 , Florence Fenollar 2 , Anderson Loudoun 3 , Alain Pascal 4 , Caroline Le Bohec 9 , Marie-Victoire Senat 7 , He ´le `ne Heckenroth 1 , Jean-Francois Coccalemen 1 , Romain Favre 8 , Dominique Luton 6 , Patrick Rozenberg 5 , Claude D’ercole 1 , Didier Raoult 2 1 Aix Marseille University, AMU, AP-HM, for the GROG, Gynépole, Obstetrics Gynecology, Marseille, France, 2 Aix-Marseille Université, Unité de Recherche sur les Maladies Infectieuses Tropicales et Emergentes, CNRS UMR 7278, INSERM U1095, Marseille, France, Infectious disease, Marseille, France, 3 Assistance Publique-Hôpitaux de Marseille, Aix Marseille Université (AMU), Department of Public Health, Marseille, France, 4 Hopital St Joseph, Obstetrics, Marseille, France, 5 Hôpital Poissy-st-Germain, Obstetrics, Poissy, France, 6 Hôpital Beaujon, AP-HP, Obstetrics, Paris, France, 7 Hôpital Kremlin Bicetre, AP-HP, Obstetrics, Paris, France, 8 Hôpitaux de Strasbourg, CMCO Schiltigheim, Obstetrics, Strasbourg, France, 9 Hôpital Morvan, Obstetrics, Brest, France OBJECTIVE: Bacterial vaginosis is a risk factor for prematurity. Despite bacterial vaginosis is often asymptomatic, the diagnosis methods are heterogeneous and based on either a clinical score and/or Gram staining, that are fastidious and unreproducible. Molecular methods have been recently developed to detect vaginal flora anomalies allowing to rationally evaluate a link between them and prematurity. STUDY DESIGN: Prospective multicenter national study including high prematurity risk pregnant women with previous preterm delivery or late abortion and/or short cervix assessed by ultrasound. Quantita- tive molecular tool targeting Atopobium vaginae, Gardnerella vagi- nalis, Lactobacillus sp, Mycoplasma hominis, and a human gene was performed using a specific real-time polymerase chain reaction assay and serial dilutions of a plasmid suspension. Bacterial vaginal loads were assessed between 14 and 34 weeks of gestation. clinicaltrial.gov NCT00484653. RESULTS: 813 patients were enrolled. High A. vaginae vaginal loads (>105/ml) was always associated with a significantly shorter interval time to delivery before 22, 28, and 32 weeks (respectively, 152.1 and 413.2 days (P¼0.001), Hazard ratio (HR 6.6, 95% CI 1.9-22.5) before 22 weeks, 149.2 and 400.6 days (P¼0.028), (HR 2.9, 95% CI 1.1-7.6) before 28 weeks, and 132.5 and 365.1 days (P¼0.014), (HR 2.3, 95 CI %1.2-4.5) before 32 weeks. S338 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2014 Poster Session V www. AJOG.org
Transcript of 687: Altered estrogenic responsiveness in the adult mouse transcriptome following neonatal exposure...
Poster Session V www.AJOG.org
Saturday, February 8, 2014 d 10:00 am e 12:00 pm d Hilton Exhibition Center
PREMATURITY, PHYSIOLOGY
Abstracts 687 e 836
687
Altered estrogenic responsiveness in the adultmouse transcriptome following neonatal exposure to17a-hydroxyprogesterone caproateSatomi Kohno1, Tomomi Sato2, Shinichi Miyagawa3,Roger Newman1, Taisen Iguchi3, Louis Guillette11Medical University of South Carolina, Obstetrics and Gynaecology,Charleston, SC, 2Yokohama City University, Graduate School ofNanobioscience, Yokohama, Japan, 3National Institute for Basic Biology,Okazaki Institute for Integrative Bioscience, Okazaki, JapanOBJECTIVE: The FDA has approved 17a-hydroxyprogesterone cap-roate (17PC), for the prevention of recurrent preterm birth. How-ever, the developmental effects of 17PC on reproductive health havenot been fully explored. Altering the steroid hormone milieu duringfetal development has potential long-term adverse consequences asobserved with diethylstilbestrol exposure in utero. Our objective wasto determine if developmental exposure to 17PC induces post-pu-bertal alterations to the female reproductive system.STUDY DESIGN: Neonatal mice (C57BL/6J) were given 5 daily in-jections SC (day 1-5) of 5 mg or 50 mg 17PC or a vehicle control(sesame oil), and were ovariectomized (OVX) at 8 wks as adults.Ten-days after OVX, 17b-estradiol (E2) or a vehicle control (sesameoil) was injected IP at 5 mg/kg Body Weight. Six-hours after E2 in-jection, mice were necropsied. Uterus, vagina, mammary gland, liver,hypothalamus and pituitary were isolated. Their transcriptomeswere analyzed by microarray analysis.RESULTS: E2-stimulated uterine mass increased in all treatmentgroups as compared with adult control treatment (P<0.01). How-ever, the response to E2 at the transcriptome level was differentamong the various neonatal treatments. E2 remarkably altered theuterine transcriptome (826 genes went up; 1085 down) in controls,whereas significantly fewer genes were altered by E2 in the uterus ofmice neonatally exposed to 5 mg 17PC: 895 up/660 down or to 50 mg17PC: 2 up/3 down. Altered sensitivity to E2 was also observed invagina, liver, mammary gland and pituitary, based on transcriptomedata.CONCLUSION: Neonatal exposure to 17PC reduced the sensitivity toE2 in multiple tissues of the adult mouse. Neonatal mice areequivalent to the 2nd trimester human fetus in terms of Müllerianduct development; thus, gestational treatment with 17PC between 16and 36 weeks may result in offspring who exhibit altered estrogensensitivity and reproductive function. This possibility demandsfurther research.
S338 American Journal of Obstetrics & Gynecology Supplement to JANUARY
Estrogenic responsiveness in transcriptom was altered by neonatal
exposure to 17a-hydroxyprogesterone caproate. Data were shown
relative mRNA levels to control � control group.
688
Atopobium vaginae reduces interval to delivery in highrisk pregnanciesFlorence Bretelle1, Florence Fenollar2, Anderson Loudoun3,Alain Pascal4, Caroline Le Bohec9, Marie-Victoire Senat7,Helene Heckenroth1, Jean-Francois Coccalemen1, Romain Favre8,Dominique Luton6, Patrick Rozenberg5, Claude D’ercole1,Didier Raoult21Aix Marseille University, AMU, AP-HM, for the GROG, Gynépole,Obstetrics Gynecology, Marseille, France, 2Aix-Marseille Université, Unité deRecherche sur les Maladies Infectieuses Tropicales et Emergentes, CNRSUMR 7278, INSERM U1095, Marseille, France, Infectious disease, Marseille,France, 3Assistance Publique-Hôpitaux de Marseille, Aix Marseille Université(AMU), Department of Public Health, Marseille, France, 4Hopital St Joseph,Obstetrics, Marseille, France, 5Hôpital Poissy-st-Germain, Obstetrics, Poissy,France, 6Hôpital Beaujon, AP-HP, Obstetrics, Paris, France, 7Hôpital KremlinBicetre, AP-HP, Obstetrics, Paris, France, 8Hôpitaux de Strasbourg, CMCOSchiltigheim, Obstetrics, Strasbourg, France, 9Hôpital Morvan, Obstetrics,Brest, FranceOBJECTIVE: Bacterial vaginosis is a risk factor for prematurity. Despitebacterial vaginosis is often asymptomatic, the diagnosis methods areheterogeneous and based on either a clinical score and/or Gramstaining, that are fastidious and unreproducible. Molecular methodshave been recently developed to detect vaginal flora anomaliesallowing to rationally evaluate a link between them and prematurity.STUDY DESIGN: Prospective multicenter national study including highprematurity risk pregnant women with previous preterm delivery orlate abortion and/or short cervix assessed by ultrasound. Quantita-tive molecular tool targeting Atopobium vaginae, Gardnerella vagi-nalis, Lactobacillus sp, Mycoplasma hominis, and a human gene wasperformed using a specific real-time polymerase chain reaction assayand serial dilutions of a plasmid suspension. Bacterial vaginal loadswere assessed between 14 and 34 weeks of gestation. clinicaltrial.govNCT00484653.RESULTS: 813 patients were enrolled. High A. vaginae vaginal loads(>105/ml) was always associated with a significantly shorter intervaltime to delivery before 22, 28, and 32 weeks (respectively, 152.1 and413.2 days (P¼0.001), Hazard ratio (HR 6.6, 95% CI 1.9-22.5)before 22 weeks, 149.2 and 400.6 days (P¼0.028), (HR 2.9, 95% CI1.1-7.6) before 28 weeks, and 132.5 and 365.1 days (P¼0.014), (HR2.3, 95 CI %1.2-4.5) before 32 weeks.
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