Silvia Caluwaerts

Agonistic Autoantibodies to the AT1 Receptor in a Transgenic Rat Model of Preeclampsia

We used rats transgenic for the human angiotensinogen (hAogen) gene and the human renin (hRen) gene and crossed the strains to produce a model of preeclampsia in the dams. The female (n=9) hAogen × male hRen cross had severe (telemetry-measured) hypertension and albuminuria, which developed during the last trimester of pregnancy and subsided after delivery. The converse cross (n=9) and control (n=9) SD rats did not. We demonstrated that the female hAogen × male hRen cross had agonistic antibodies capable of activating the angiotensin (Ang) II AT1 receptor (AT1R-AA) and defined the epitope on the receptor’s second extracellular loop. The phenomenon also occurs in humans with preeclampsia. The rats displayed renal histology reminiscent of preeclampsia, including fibrin deposition confined to the glomeruli. The complement system was activated in glomeruli and IgG deposits were present that may represent AT1R-AA. Finally, we observed an atherosis-like lesion in the spiral arteries of the placental bed, which we called placental-bed arteriolosclerosis. Our model may be relevant to preeclampsia in humans.

Adipokine profile and C-reactive protein in pregnancy: effects of glucose challenge response versus body mass index.

Objective: To test the hypothesis that gravidas who have an abnormal response to glucose loading have dysfunctional adipose tissue cells that produce more insulin resistance-inducing and proinflammatory adipokines but less insulin-sensitizing adipokines. Methods: We performed a nested case-control study within a larger sample of gravidas who had a glucose challenge test (GCT) at 24-29 weeks; we compared 73 cases with an abnormal GCT (>8.3 mM) and 146 controls with a strictly normal GCT (<7.2 mM) matched for body mass index (BMI) and height (mean diference between cases and controls: 0. 1 kg/mn2 and 1 cm, respectively). We measured plasma insulin, adipokines (leptin, adiponectin, resistin, tumor necrosis factor [TNF]-α, interleukin [IL]-6), soluble leptin receptor (sOb-R), the main leptin-binding protein, and C-reactive protein (CRP). Results: The cases showed a 48% increase in insulin concentrations and a 27% increase in TNF-α concentrations compared to the controls (both P < .0001), but leptin, sOb-R, IL-6, and adiponectin, as well as CRP, concentrations were comparable between cases and controls. In the whole group (n = 219), BMI was correlated with insulin, leptin, IL-6, and CRP, and inversely with sOb-R and adiponectin concentrations (all P < .0003). Conclusions: Plasma leptin, sOb-R, IL-6, and adiponectin, as well as CRP, are strongly related to BMI ingravidas at 24-29 weeks gestational age but not to the glucose loading response. However, TNF-α is higher in women with an abnormal GCT. Further studies should disclose the source of increased TNF-α in these women, and to assess whether TNF-α is causally related to glucose intolerance during pregnancy.

Growth characteristics of diabetic rat ectoplacental cones in vivo and in vitro

Aims/hypothesis. To investigate the outgrowth of the ectoplacental cone in diabetic rats in vivo and in vitro.¶Methods. Female Wistar rats were injected intraperitoneally with streptozotocin (75 mg/kg body weight, n = 15), or with control buffer (n = 27) 3 days before mating. On day 9 (day 1 = copulation plug) decidual swellings were weighed and the volume and mitotic index of the embryo and ectoplacental cone were estimated. Also, ectoplacental cones were cultured either in the presence of decidual cells from pseudopregnant diabetic rats or in high glucose concentration media. Cultures were evaluated by the daily outgrowth and by the proportion of giant cells and proliferating cells on day 5.¶Results. In diabetic rats on day 9, the weight of the decidual swellings and the mitotic index in the ectoplacental cone were lower compared with controls (p < 0.0001 and p < 0.05, respectively). In vitro, control ectoplacental cones in the presence of decidual cells from diabetic rats showed a slight reduction in outgrowth on day 3 and 5 of culture. Outgrowth of diabetic ectoplacental cones in high glucose concentration medium was impaired on day 1 (p < 0.0005) compared with control ectoplacental cones in control medium, and on day 1 and 2 (both p < 0.005) compared with control ectoplacental cones in high glucose concentration medium. In control medium, the outgrowth of diabetic ectoplacental cones was impaired on day 1 (p < 0.05), compared with control ectoplacental cones. Proliferation was stimulated in diabetic ectoplacental cone cultures.¶Conclusion/interpretation. These data suggest that the outgrowth of diabetic ectoplacental cones is impaired by high glucose concentrations. [Diabetologia (2000) 43: 939–945]

Differential effects of IL-11 on rat blastocysts and decidua during the peri-implantation period.

PROBLEM: To study effects of interleukin‐11 (IL‐11) on blastocyst development and decidualization.