cesarean delivery increased with advancing gestational age from. 39 to 41 weeks, as did the rate of forceps-assisted delivery and 3rd or 4th degree perineal ...
Poster Session I cesarean delivery increased with advancing gestational age from 39 to 41 weeks, as did the rate of forceps-assisted delivery and 3rd or 4th degree perineal laceration, p 0.001 (table). The rate of shoulder dystocia trended up with advancing gestational age, but did not reach significance (p¼0.06). When compared to women without diabetes, the absolute rates of all examined complications were increased, however, the gestational age trends for women with A1DM were no more pronounced (figure). CONCLUSION: In women with A1DM the rate of maternal morbidities increases with advancing gestational age at delivery, though no more pronouncedly than in the non-diabetic population. Put another way, expectant management at term in women with A1DM poses no greater incremental risk than in non-diabetic women.
ajog.org receptor beta (IR-b) and its downstream target insulin receptor substrate 1 (IRS-1) and glucose transporters (GLUT2; GLUT4). STUDY DESIGN: Rat dams had ad libitum access to filtered drinking water (Control) or drinking water with BPA (5mg/L; BPA) from 2 weeks prior to mating and throughout pregnancy and lactation. Offspring litters were standardized to 4 males and 4 females and nursed by the same dam. At weaning, BPA exposure was removed from all offspring. Glucose tolerance was tested at 6 weeks and 6 months. Liver and skeletal muscle was collected from 3 week-old and 10 month-old offspring for protein expression (Western Blot) of IRb, IRS-1, GLUT2, and GLUT 4. RESULTS: Male BPA offspring had impaired glucose tolerance at 6 weeks and 6 months. Six month offspring had higher glucosestimulated insulin secretion. Male BPA offspring had higher liver protein abundance of IR-b (2-fold), and IRS-1 (1.5-fold), while GLUT-2 was 0.5-fold of the control at 3 weeks. In adult male BPA offspring the abundance of IR-b was higher (2-fold) and GLUT-4 was 0.8-fold of the control in skeletal muscle. Maternal BPA did not affect glucose tolerance or insulin signaling in female offspring at any age. CONCLUSION: Maternal BPA had sex- and tissue-specific effects on insulin signaling components, which may contribute to increased risk of glucose intolerance in male offspring. At 3 weeks the main site of perturbation in insulin signaling was the liver, while at 10 months, the perturbation was in the skeletal muscle. The glucose transporters were consistently altered at both ages and may contribute to glucose intolerance. These data suggest that maternal BPA exposure should be limited during pregnancy and lactation.
143 Maternal hyperglycemia causes reduced arterial smooth muscle cell outgrowth in chorionic plate arteries from human placenta Luckey C. Reed, Nicholas Ieronimakis, Peter G. Napolitano 1
Madigan Army Medical Center, Tacoma, WA
OBJECTIVE: Diabetes in pregnancy is associated with an increased risk
142 Maternal bisphenol-A (BPA) exposure programs male offspring glucose tolerance and alters hepatic and skeletal muscle insulin signaling protein expression Kristina Galyon, Farnoosh Farshidi, Mina Desai, Michael G. Ross, Juanita K. Jellyman 1
Dept. of Ob/Gyn, LABioMed at Harbor-UCLA Med. Ctr., Torrance, CA
OBJECTIVE: The obesogenic and diabetogenic effects of the envi-
ronmental toxin BPA during critical windows of development are well-recognized. Liver and skeletal muscle play a central role in the control of glucose production, utilization and storage. We hypothesized that maternal BPA exposure is associated with programmed glucose intolerance and disrupts insulin signaling in liver and skeletal muscle. We determined the protein expression of hepatic and skeletal muscle insulin signaling molecules including insulin
for morbidity and mortality and is thought to be the result of hyperglycemia. In a previous study by Wilkes, et al (1994), they observed a blunted fetal-placental arteriole response to thromboxane using perfused diabetic placentas. Therefore, we hypothesize that hyperglycemia impairs vascular smooth muscle cells and is responsible for the abnormalities seen in thromboxane-mediated vasoconstriction. The objective of our study was to evaluate fetalplacental artery smooth muscle cell growth after exposure to hyperglycemia in a placenta perfusion model. STUDY DESIGN: Placentas were acquired from normal term nondiabetic patients undergoing a repeat c-section. Two cotyledons from each placenta were isolated and dually perfused. A continuous infusion of either 100mg/dl or 300mg/dl perfusate was administered into the maternal circulation for 30 min. Then, a bolus dose of thromboxane mimetic (U46619) was injected into fetal circulation. Thirty minutes following exposure to U46619, placenta arterial explants were cultured to measure smooth muscle cell outgrowth. For this assay, fetal-placental arteries were excised and stripped from surrounding stroma and adventitia. Explants cut from these vessels were then seeded on collagen IV coated plates and cultured for 7 days. At day 8, explants were fixed and stained for immunofluorescence analysis of smooth muscle cell outgrowth. RESULTS: The phenotype of these cells was confirmed by staining for alpha-smooth muscle actin, a marker commonly used to stain arterial smooth muscle in vivo. Analysis revealed a significant reduction in percent of smooth muscle cell outgrowth from fetal-
S94 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2016
Poster Session I
ajog.org placental arterioles perfused under hyperglycemic conditions as compared to the normal glycemic perfusate and the preperfused control. (Figure 1) CONCLUSION: Hyperglycemic infusion of maternal circulation in a dual perfusion placenta model results in attenuation of smooth muscle cell outgrowth of fetal-placental arteries. This impairment of cell growth was noted with only 30 min. of exposure. These findings suggest a possible mechanism for the blunted vascular response seen in fetal-placental arteries from diabetic placentas.
characterization of histopathological changes can be performed to assess for regulation of vascular integrity and tone.
145 Maternal protein restriction causes decreased sex hormone concentrations in the offspring and are associated with peripheral insulin resistance Chellakkan Selvanesan Blesson, Amy Schutt, Daren Tanchico, Meena Balakrishnan, Uma Yallampalli, Chandra Yallampalli 1
Baylor College of Medicine, Houston, TX
OBJECTIVE: Our objective was to identify if endocrine dysfunction
144 Pathologic vascular response in fetal-placental arteries constricted with thromboxane after exposure to maternal hyperglycemia in a human dual perfusion placenta model Luckey C. Reed, Nicholas Leronimakis, Peter G. Napolitano 1
Madigan Army Medical Center, Tacoma, WA
OBJECTIVE: Hyperglycemia in pregnancy is known to be associated
with increased complications and has been shown to cause altered responses in ex-vivo fetal-placental vasculature following exposure to thromboxane. However, the pathogenesis of vascular dysfunction in relation to hyperglycemia is not well understood or characterized. In our prior work we found an exaggerated vascular response in fetalplacental arterial perfusion when exposed to hyperglycemia. Our objective was to further characterize this finding by evaluating the fetal-placenta arteries after perfusion using immunohistochemical staining. STUDY DESIGN: We collected cotyledons from placentas of normal, unlabored, term patients undergoing a repeat c-section. Two cotyledons from each placenta were isolated and dually perfused with either a glucose concentration of 100mg/dL (euglycemia) or a glucose concentration of 300mg/dL (hyperglycemia). After 30 min., cotyledons were challenged with a bolus of the thromboxane mimetic U44619, to asses for altered function resulting from a hyperglycemic perfusate. Following constriction, the perfused cotyledons were processed for immunohistological analysis using smooth muscle specific markers. (alpha-smooth muscle actin). RESULTS: We observed that the vasoconstrictor effects of thromboxane mimetic U46619, a potent vasoconstrictor, were exaggerated in placenta perfused with a hyperglycemic perfusate, as compared with euglycemic perfusate. Histological analysis of cotyledens pre and post-perfusion (Figure 1), reveals increased stenosis in addition to altered vascular architecture with 300mg/dL. In particular, the hyperglycemic perfusate resulted in stenosis of the lumen and hypertrophy of the smooth muscle media. CONCLUSION: The exaggerated vascular pressure response we observed with the hyperglycemic perfusion correlated with alterations in fetal-placental vascular morphology. Further
leading to decreased sex hormone levels will precede the development of T2D in LP-programmed offspring. STUDY DESIGN: We have previously characterized a lean type 2 diabetes (T2D) rat model using gestational low protein diet programming. Pregnant rats were fed control (20% protein) or isocaloric LP (6%) diet from gestational day 4 until delivery. Normal diet was given to mothers after delivery and to pups after weaning until sacrifice. Male and female offspring from LP diet given dams developed glucose intolerance and insulin resistance at 4 months and the degree of glucose intolerance worsened with age. We used enzyme immune assay to measure the levels of testosterone (T) and estrogen-17b (E2) in plasma. We also profiled the expression of key genes involved in steroidogenesis in testis and ovary using qPCR to identify altered gene expression that could affect the synthesis of T and E2. RESULTS: Plasma steroid measurements showed that in LP programmed rats, males have low T levels (1540pg/ml in LP vs. 5745pg/ ml in controls) and females have low E2 levels (2.3pg/ml in LP vs. 4.4pg/ml in controls, measured during diestrus) when compared to their respective controls. In males, key enzymes involved in T synthesis in testes are dysregulated. Cyp11a1 which is responsible for cholesterol side chain cleavage and Hsd17b1 which converts androstenedione to T are downregulated in LP rats despite the compensatory upregulation of StAR gene. StAR gene is responsible for the transfer of cholesterol to mitochondria to initiate steroidogenesis. Further Cyp 19 (aromatase) which converts T to E2 is also upregulated in males. In females LP rats, StAR gene is downregulated. Despite the compensatory upregulation of aromatase and Hsd17b7 which convert androstenedione to T and estrone to E2, respectively, E2 levels are lower in LP females. CONCLUSION: Rats that develop T2D by LP programming have compromised gonadal steroidogenesis leading to reduced circulating concentrations of T and E2 in males and females, respectively.
Supplement to JANUARY 2016 American Journal of Obstetrics & Gynecology
S95
