35

258 SPO Abstracts

All EXPERIMENTAl Al60RITIll Of FACTORS CRITICAL FOR DIABETIC TERATOGENESIS. Reece EA. Pinter r. Hobbins JC. !laftolin F. Depart.ent of OIl/GYM. Yale University School of Medicine. flew Haven. CT.

Although c1 inlca1 and experiEllta1 studies suggest that perturbations in .etabo1lc control ... y be causative in diabetic teratogenesis. I!IIIbryopathy does not always occur even under the afo_tioned conditions. In an att""",t to dete ... ine critical factors for diabetic teratogenesis. IIII! """,loyed the post­l..,lantation rat I!IIIbryo culture as a .ode1 for Investigation. The effect of various factors on I!IIIbryonic deve1~t IIII!re studied: Variations in gestational age and varying duration of exposure to aberrant fuel .1 xtures and envi rDnEIIta 1 condi t Ions. including increase In glucose concentrations (noru1 = 150 lIg/d1) to achieve a level Z to 6 ti.es noru1; hypoxia. hyperthe ... la and excess VIt_in A. Malforutlons IIII!re Induced In a dose-related fashion: a ZOX rate at Z ti.es control glucose concentrations; a 50X rate at 3 ti .. control. and a 100X rate at 6 ti.es control. A .Inl_ of exposure ti.e to hyperg1yc.,.ia of blo hours was required to induce anoElies. If exposure to the 100X teratogenic dose of hyperg1yceaia was initiated on Day 10 .... lforutions IIII!re pri ... rlly defects of the neural tube; on Day 11. principally cardiac defects; and beyond Day 11.5. no defects IIII!re induced. Other altered environaenta1 conditions. such as hyperthe ... ia. hypoxia. excess Vit_in A. also Induced ... lforutlons. but within the critical window (Day 10 - Day 11) and following a .ini_ exposure ti.e (! Z hrs). An a1gorit .. for diabetic teratogenesiS was generated. based on the above and other factors and extrapolations proposed for the huEn. Conclusion: These data indicate that diabetic teratogenesis results fro. the accidental synchronization of a n..mer of deve10!l!!!l!nta1 events involving. Inter alia. aberrant environnenta1 and fuel _ixtures. a critical gestational age. and a _ini_ eXPOsure time. Therefore. aSYnchrony of these events wool d not resu 1t in dysmorohooenes is even in the presence of ... rked aberrations in llletabolic fuels.

36 GENE EXPRESSION DURING PLACENTAL DEVELOPMENT. L. Dungy, M.D., T.A. Siddiqi, M.D., S. Khan", M.D. University of Cincinnati Medical Center, Cincinnati, OR USA.

During embryogenesis and placentation, tissue growth and differentiation occur in a sequential and predetermined order, i.e. specific genes coding for particular proteins are turned on and off in a precise, well-regulated manner. Knowledge with respect to regulatory factors involved in these processes is limited but experimental data supporting a role for proto­oncogenes and growth factors is available. We are currently studying the teleologic expression of early response proto-oncogenes c- jun, c-fos and Transforming Growth Factor-.B (TGF-.B) in the human placenta. In this report, we describe our results with respect to TGF-.B, a factor with growth inhibitory effects on both normal and malignant cell types. Total RNA was isolated from placental tissues (gestational ages: 6, 8, 14, 17, 20, 33 and 40 weeks) by the procedure of Chomzenski and Sacchi. Northern blot analysis indicated the maximal expression of TGF-.B in I7 week gestation placentae with a lack of expression at earlier or later gestational ages. Trophoblastic invasion of the myometrium is largely restricted to the 8th through 18th weeks of gestation. We conclude that the expression of TGF-.B during placentation and (embryogenesis) is developmentally regulated and may play a role in the inhibition of myometrial trophoblastic invasion. We plan to perform in-situ hybridization procedures to further define the specific placental cell types which express proto­oncogenes and growth factors.

Januar) 1991 Am J Ob,tet Cvnecol

37 aM'ARISCN OF EARLY AMNICCENI'ESIS VERSUS CRORICNIC vnms SAMPLING AND HIDOOMESI'ER AMNICCENI'ESIS, B .. ABsel, M.D. x, M. Jassani, M.D., L. Dicke!lIEI1, Fh.D. x, S. l.ewisx, J.C. Veille, M.D., University MicLbnald \.Jaren's Hospital, Case Western Reserve University, Cleveland, Grio

Early amniocentesis may be a safe alternative for I\OIEll M10 desire genetic evaluation in early pregnancy. During a 46 lIDnth period fran Septenber, 1986, to July, 199:), 140 consecutive chorionic villus sampling (CVS) procedures \<.ere perfoJ:TIed transcervica1ly at 9-12 weeks gestation, 218 consecutive early anmiocenteses (FA) \<.ere perfoITIEd transabdaninally at 11-14 weeks gestation and 218 consecutive control midtr:i.rrEster anmiocenteses (MA) \<.ere perfoITIEd transabdaninally at 16-18 weeks gestation. All spec:inEns in each group \<.ere obtained by one operator and \<.ere cultured and analyzed in one cytogenetics laboratory. The maternal age, race, and indication for the procedure \<.ere similar in all three groups with the exception of I\OIEll with certain indications electing CVS and/or FA versus MA after appropriate cOlll1Seling . Selected results are shown below:

M=thod CVS FA Failed Sampling 22/140 2/218 Pregnancy Loss Within 4 Weeks 7/126 2/210 Pregnancy Loss After 4 Weeks 3/119 1/2CB

and <28 Weeks Gestation

MA 0/218 1/216 1/215

p<O.CX)l p<O.CX)l p=O.1l9

Preterm Birth Rate 5/99 6/184 3/204 p=O.2CO We conclude that FA is an acceptable alternative for I\OIEll

who desire early genetic pregnancy evaluation.

38 DIAGNOSIS OF PREMATURE RUPTURE OF FETAL MEMBRANES BY

THE MEASUREMENT OF INSULIN-LIKE GROWTH FACTOR BINDING PRarEIN-I IN CERVICAL SECRETION

Eeva-Mana Rutanenx and Frednka Pekonenx Department of Obstetncs and Gynecology, Umversity Central HospIlal, and Mmerva Institute for MedIcal Research,Helsmkl, Finland

Insulin-hke growth factor bindmg protem-l (IGFBP-I) IS a 25 kD protein synthesized by decidua and present m the amniotIc fluid at conccntrationslOOO-fold hIgher than those In maternal serum In thIS

study, we used two monoclonal antIbody-based sandWIch assays to measure IGFBP-I levels m swab samples obtamed from cervIx In 54 patIents with chnically mtact membranes (confirmed afterwards) and In

35 patIents after spontaneous or arleflclally ruptured membranes WIth or wIthout labor. Paired sample; of serum and amnIOtIc flUId (n=25) obtained by amniocentesIs at 24 to 38 weeks' gcstatlOTI were abo studted. In addItIOn, IGFBP-l level was measured m maternal unnc (n=31), and cerVIcal secretIOn of non-pregnant women (n=20) as well as in semmal plasma (n=IO). The medIan IGFBP-I concentration m

ammotIc flUId was 130 x 103ng/ml (range from 800 x 103 to I x 104

ng/ml), and m paIred serum samples It was 240 ng/ml (range 50 to 500 ng/ml). In the pattents WIth ruptured membranes, the medIan lGFBP-l

value m cervical samplings was 1900 ng/ml (range 175 to 2 , 104

ng/ml), whereas in patIents WIth mtact membranes It ranged from undetectable to 90 ng/ml. No IGFBP-I was detected in cerVIcal secretions of nonpregnant women, and In maternal unne as well a~ In

semmal plasma the levels were barely detectable These data show that the measurement of IGFBP-l from cerVical secrellon provldc!-. a hIgh degree of discnmmation between ammotlc flUId and mterfenng body fluids, bemg thus extremely useful m patIents from whom other dIagnostIc procedures have not estabhshed the diagnOSIs of ruptured fetal membranes.