Poster Presentation Australasian Diabetes in Pregnancy Society Annual Scientific Meeting 2019

The impact of pre-pregnancy weight modulation on placental structure and inflammation in mouse models of diabetes and obesity (#68)

Natassia Rodrigo 1 2 , Jasmin Russell 3 , Hui Chen 3 , Carol Pollock 2 4 , Sarah Glastras 1 2
  1. Endocrinology, Royal North Shore Hospital, St Leonards, NSW, Australia
  2. University of Sydney, Sydney, NSW, Australia
  3. University of Technology, Sydney, Sydney, NSW, Australia
  4. Renal Department, Royal North Shore Hospital, Sydney, NSW, Australia

Background and aims:

Diabetes and obesity during pregnancy are risk factors for preeclampsia, preterm delivery, and even stillbirth. Placental dysfunction plays a key role in this situation. Placentas of obese mothers show increased inflammation. To date, no studies have addressed whether pre-conception maternal weight loss can reduce placental inflammation in obese mothers. Thus, we aimed to determine if weight loss prior to pregnancy, either with diet modification or therapeutic intervention with liraglutide, restores normal placental structure and function.

 

Materials and Methods:

Female C57BL/6 mice were fed a high fat diet (HFD) for 8 weeks versus normal chow diet as control. In the obese dams, diet modification (switch to chow diet) or liraglutide treatment (0.3mg/kg s.c. for 4 weeks) was used to induce pre-conceptional weight loss. Maternal anthropometric measures, glucose tolerance and metabolic markers were measured before the intervention, after intervention and at late gestational age. Pregnant dams were sacrificed at gestational Day 18-20. Maternal blood and placenta were collected. Pregnancy rates, and foetal number, were recorded. Immunohistochemistry, Western blotting and real-time PCR were used to measure placental inflammation and structure.

Results:

Prior to the dietary intervention or liraglutide, the dams fed a HFD had greater body weights and reduced glucose tolerance compared to chow-fed dams (p < 0.005). Following intervention with liraglutide or diet modification, the body weight and glucose intolerance were reduced compared to non-treated HFD-fed dams (both P< 0.005).  Intervention with liraglutide or diet improved the conception rates in obese dams and the foetal number and size were restored to that of normal weight dams. Inflammatory markers (e.g., MCP-1, IL-6, F4/80, CD68) were lower in the placentas of dams in the intervention groups compared to non-treated obese dams.  

Conclusions:

Preconception weight reduction improves maternal weight and glucose tolerance prior to pregnancy, and increased pregnancy rates. It also reduces placental inflammation, which may optimise its function.