Infant and childhood obesity is known to be a risk factor for obesity and related diseases later in life. Obese women are prone to deliver more likely infants with elevated adipose tissue mass. The underlying mechanisms and the functional role of the placenta during late pregnancy are not well understood yet. The main objective of this thesis was to investigate whether maternal pre-pregnancy obesity impacts fatty acid (FA) transfer across the human placenta and to understand the distribution of exogenously provided FAs between placental and fetal compartment. This study aimed also to examine the effect of maternal pre-pregnancy obesity on placental genes and proteins, which are involved in lipid and FA uptake, metabolism, and transport. Maternal-to-fetal free FA (FFA) transfer was examined in placentas of lean (pre-pregnancy body mass index (BMI) ≤25 kg/m²) and obese women (BMI ≥30 kg/m²) by ex-vivo perfusion approach. 13C-labelled FFAs bound to albumin were offered to the maternal compartment and transfer of 13C FFAs to the fetal compartment was followed by gas chromatography (GC) – mass spectrometry. Distribution of FAs to different lipid classes of maternal and fetal perfusates was measured by thin-layer chromatography and GC. Target specific gene expression, determined by nCounter technology, as well as protein expression and localization were performed in placental tissue of lean and obese women. Results from perfusion experiments showed that transferred palmitic, oleic, and linoleic acid are mainly restored in phospholipids (PL) and as FFAs in fetal perfusates. Minor amounts of palmitic acid were also detectable in cholesterol esters and triglycerides (TG). Maternal-to-fetal transfer of palmitic, oleic, and linoleic acid is slightly higher in obese compared to lean placentas. In placentas of obese women the transfer of docosahexaenoic acid (DHA) is significantly (P=0.040) elevated by 44% compared to lean placentas. By stratifying the cohort according to fetal sex, comparable absolute transfer of all FFAs was observed in obese male and lean female placentas. Again, DHA transfer was significantly (P
Maternal-to-fetal transfer of fatty acids across the human placenta
Hirschmugl, B. (Author). 2019
Student thesis: Doctoral thesis