title: Adverse factors increase preeclampsia-like changes in pregnant mice with abnormal lipid metabolism.
abstract: BACKGROUND
  Preeclampsia (PE) is a multifactorial pregnancy complication. Maternal underlying condition and adverse factors both influence the pathogenesis of PE. Abnormal lipid metabolism as a maternal underlying disease may participate in the occurrence and development of PE. This study aimed to observe the effects of adverse factors on PE-like symptoms of pregnant mice with genetic abnormal lipid metabolism.
  
  
  METHODS
  Apolipoprotein C-III (ApoC3) transgenic mice with abnormal lipid metabolism were subcutaneously injected with L-arginine methyl ester (L-NAME) or normal saline (NS) daily starting at Day 7 or 16 of pregnancy (ApoC3+L-NA and ApoC3+NS groups), and wild-type (WT) mice served as a control (WT+L-NA and WT+NS groups). All mice were subdivided into early and late subgroups by injection time. The mean arterial pressure (MAP) and urinary protein were measured. Pregnancy outcomes, including fetal weight, placental weight, live birth rate, and fetal absorption rate, were analyzed. Pathologic changes in the placenta were observed by hematoxylin-eosin staining. One-way analysis of variance, t-test, and χ(2) test were used for statistical analysis.
  
  
  RESULTS
  MAP significantly increased for ApoC3+NS groups compared with WT+NS groups (P < 0.05), without significant difference in urine protein. Following L-NAME injection, MAP and urinary protein significantly increased for ApoC3+L-NA and WT+L-NA compared with the corresponding NS groups (P < 0.05), and the increase for ApoC3+L-NA was more obvious. Urinary protein levels in early ApoC3+L-NA and WT+L-NA significantly increased compared with the corresponding late groups (P < 0.05). Fetal absorption rate significantly increased and fetal and placental weights significantly decreased in early ApoC3+L-NA and WT+L-NA compared with the corresponding NS groups (P < 0.05), without significant difference in late ApoC3+L-NA and WT+L-NA groups. Fetal weight in early ApoC3+L-NA was significantly lower than in early WT+L-NA group (P < 0.05). Morphologic examination of placentas from early ApoC3+L-NA and WT+L-NA groups showed varying degrees of fibrinoid necrosis.
  
  
  CONCLUSIONS
  ApoC3 transgenic mice with abnormal lipid metabolism showed gestational hypertension. Adverse factors and early effect time could aggravate the PE-like symptoms for ApoC3 transgenic mice.
authors.affiliation: Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China. Email: zi_yang@email.com.
authors.forename: Zi
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Yu
mesh_terms: D000818:Animals; D053305:Apolipoprotein C-III / Q000235:genetics / Q000378:metabolism; D005260:Female; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D053305:Apolipoprotein C-III; D019331:NG-Nitroarginine Methyl Ester