Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

A Disintegrin and Metalloproteinase With Thrombospondin Motifs (ADAMTS) -1 and -15 expression is upregulated in the murine placenta following high fat feeding (#27)

Bryony A McNeill 1 , Rachael E Marshall 1 , Nicholas J Wong 1 , Eileen V Cole 1 2 , Nicole Stupka 1 , Leonard G Forgan 1
  1. School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia
  2. Eastern Health Pathology, Box Hill, VICTORIA, Australia

The consumption of a high fat diet (HFD) before and during pregnancy is associated with detrimental outcomes for both mother andĀ fetus. Maternal HFD affects fetal growth, resulting in increased birth weight and elevated risk of developing obesity, diabetes and metabolic syndrome in adulthood. The placenta is a critical determinant of intrauterine growth, and its structure and function are altered by suboptimal maternal diet. Despite much research investigating how HFD affects the placenta and, consequently, fetal growth and development, the molecular mechanisms have not been fully elucidated. HFD feeding alters extracellular matrix (ECM) remodelling in metabolically active tissues, which has profound biological implications as the ECM regulates the bioavailability of growth factors and cytokines. The effect of HFD on placental ECM remodelling and function are not known. Here, we used a mouse model to investigate the effects of HFD on the expression of the ECM proteases ADAMTS-1, -5 and -15; important proteoglycan proteases in reproductive tissues. Mice were fed a HFD (40% energy from lipids, n=7) or control diet (14% energy from lipids, n=8) from 3 weeks prior to conception until day 17 of pregnancy (term = day 21). At termination of pregnancy on day 17, fetal weight was higher in the HFD group (P<0.05). Despite no difference in placental weight or evidence of pathology, mRNA transcript abundance of ADAMTS-1 and -15 was significantly elevated in placentas from HFD-fed mice (ADAMTS-1 P<0.05; ADAMTS-15 P<0.01). Immunohistochemical analysis revealed strong staining for ADAMTS-1, -5 and -15 in the decidual zone of the placenta, supporting a possible role in placental invasion. Current work is aimed at identifying the substrates for ADAMTS proteases in the placenta. These results demonstrate that ECM remodelling is affected by maternal diet during pregnancy, and highlight its importance as a new target for understanding fetal growth and developmental programming.