Effects of intrahepatic cholestasis on morphology of fetal lungs in pregnant rat

Abstract

To investigate the influence of intrahepatic cholestasis of pregnancy (ICP) on the pulmonary morphologic changes of fetal rats. Twenty pregnant SD rats at 15 days of gestations were randomly divided into ICP and control group. Rats in the ICP group were subcutaneously injected with 17-alpha-ethinylestradiol and progesterone for 5 consecutive days to establish the rat ICP model, and those of the control group received subcutaneous injection of sirasimeyu also for 5 days. The levels of serum alanine aminotransferases (ALT), aspartate transamlnase (AST), and total bile salt (TBA) were measured before and after the treatment, respectively. Maternal rats were sacrificed on 21 days of gestations and hysterotomies were performed immediately. Histopathologic changes of maternal rats' livers and fetal lungs were observed under light and electron microscopes. (1) The maternal serum levels of ALT, AST, and TBA showed no significant difference between the ICP and control group [ALT: (55+/-15) vs (49+/-12) U/L; AST: (146+/-16) vs (145+/-20) U/L; TBA: (13+/-4) vs (14+/-4) micromol/L, P>0.05, respectively] before the ICP models were established, but higher levels were shown in the ICP group after [ALT: (94+/-12) vs (59+/-17) U/L; AST: (245+/-26) vs (163+/-27) U/L; TBA: (44+/-16) vs (17+/-3) micromol/L, P<0.05, respectively]. (2) The livers of maternal rats' in the ICP group were gloomy with blurred margins, however those of the control group were normal. Microscopic observed swollen and degenerated hepatocytes with narrowed hepatic sinusoid, dilated bile duct and necrosis of hepatocytes occasionally in the ICP group, while the morphology of hepatocytes and structures of lobuli hepatis in the control group were normal. (3) The fetal pulmonary tissues in the ICP group were dark, and normal in the control group. Histopathologic examination showed matured fetal pulmonary tissues with dilated and congested interstitial lung capillaries, thickened alveolar septum, mild focal inflammatory exudation and focal hemorrhage in alveolus. Furthermore, reduced microvilli, mitochondrion vacuolization, cytoplasm disintegration and increased lamellar body evacuation were observed in type II pneumonocytes in ICP group under light and electron microscopes. While fetal pulmonary tissues of the control group did not show any significant lesions. Rat model of ICP can be established with the combination of estrogen and progestin. Hyperbileacidemia in ICP rat may lead to pathological changes in fetal pulmonary tissues.