Activities of cyclooxygenases, and levels of prostaglandins E2 and F2alpha, in fetopathy associated with experimental diabetic gestation.

AIM

The present study investigated the cyclooxygenase (COX) pathway to elucidate any changes that may be involved in the mechanism(s) underlying diabetic fetopathy.

METHODS

Diabetes was induced in female rats (n=12) by two successive daily injections of 55 mg/kg streptozotocin, while control animals (n=10) were injected with a buffer solution; hyperglycaemia was confirmed by blood glucose levels greater than 11 mmol/L. The study female rats were made pregnant and, on day 15 of gestation, the rats were sacrificed, and the fetuses, placentas and membranes dissected out of the uterine horns. Following morphological examination, the fetuses, placentas and membranes were homogenized, and used to measure COX activities and prostaglandin (PG) E(2) and PGF(2alpha) levels.

RESULTS

Fetuses from diabetic mothers exhibited significantly (P<0.05) shorter crown-to-rump lengths, lower body weights and heavier placental weights. The activity of COX-1 in the fetuses, placentas and membranes from diabetic mothers represented a small percentage of total COX activity compared with that of COX-2. The presence of a COX-1 inhibitor in the control and diabetic rats was investigated and found to be negative. The activity of COX-2 in malformed fetuses from diabetic mothers was significantly lower (P<0.05) compared with non-malformed fetuses from control and diabetic mothers. The mean level of PGE(2) in fetuses from diabetic mothers was significantly (P<0.05) lower than that in controls. In contrast, the biggest increases in PGF(2alpha) were observed in the malformed diabetic fetuses, placentas and membranes.

CONCLUSION

The increased production of PGF(2alpha) probably proceeds, at least in part, independently of the COX pathway and via the isoprostane route. However, it is unclear whether the relatively high levels of PGF(2alpha) are causally related to, or simply coincidental with, fetal malformation.