Placental transfer of fatty acids and fetal implications.

Considerable amounts of long-chain polyunsaturated fatty acids (LC-PUFAs), particularly arachidonic acid and docosahexaenoic acid (DHA, 22:6n-3), are deposited in fetal tissues during pregnancy; and this process is facilitated by placental delivery. Nevertheless, the mechanisms involved in LC-PUFA placental transfer remain unclear. Stable isotope techniques have been used to study human placental fatty acid transfer in vivo. These studies have shown a significantly higher ratio of (13)C-DHA in cord to maternal plasma compared with other fatty acids, which reflects a higher placental DHA transfer. In addition, a selective DHA accumulation in placental tissue, relative to other fatty acids, has been reported. The materno-fetal transfer of fatty acids is a slow process that requires ≥12 h. A high incorporation of dietary (13)C-DHA into maternal plasma phospholipids appears to be important for placental uptake and transfer. DHA in cord blood lipids correlates with placental messenger RNA expression of fatty acid transport protein (FATP)-4, compatible with a role of FATP-4 in DHA transfer. Impaired materno-fetal LC-PUFA transport has been proposed in pregnancies complicated by abnormal placental function (eg, due to gestational diabetes mellitus or intrauterine growth restriction), which should be addressed in future studies. Given that placental DHA transfer is important for child outcomes, elucidation of its potential modulation by transport mechanisms, maternal diet, and disease appears to be important.

Cord blood Vα24-Vß11 natural killer T cells display a Th2-chemokine receptor profile and cytokine responses.

BACKGROUND: The fetal immune system is characterized by a Th2 bias but it is unclear how the Th2 predominance is established. Natural killer T (NKT) cells are a rare subset of T cells with immune regulatory functions and are already activated in utero. To test the hypothesis that NKT cells are part of the regulatory network that sets the fetal Th2 predominance, percentages of Vα24(+)Vß11(+) NKT cells expressing Th1/Th2-related chemokine receptors (CKR) were assessed in cord blood. Furthermore, IL-4 and IFN-γ secreting NKT cells were quantified within the single CKR(+) subsets. RESULTS: Cord blood NKT cells expressed the Th2-related CCR4 and CCR8 at significantly higher frequencies compared to peripheral blood NKT cells from adults, while CXCR3(+) and CCR5(+) cord blood NKT cells (Th1-related) were present at lower percentages. Within CD4(neg)CD8(neg) (DN) NKT cells, the frequency of IL-4 producing NKT cells was significantly higher in cord blood, while frequencies of IFN-γ secreting DN NKT cells tended to be lower. A further subanalysis showed that the higher percentage of IL-4 secreting DN NKT cells was restricted to CCR3(+), CCR4(+), CCR5(+), CCR6(+), CCR7(+), CCR8(+) and CXCR4(+) DN subsets in cord blood. This resulted in significantly decreased IFN-γ /IL-4 ratios of CCR3(+), CCR6(+) and CCR8(+) cord blood DN NKT cells. Sequencing of VA24AJ18 T cell receptor (TCR) transcripts in sorted cord blood Vα24Vß11 cells confirmed the invariant TCR alpha-chain ruling out the possibility that these cells represent an unusual subset of conventional T cells. CONCLUSIONS: Despite the heterogeneity of cord blood NKT cells, we observed a clear Th2-bias at the phenotypic and functional level which was mainly found in the DN subset. Therefore, we speculate that NKT cells are important for the initiation and control of the fetal Th2 environment which is needed to maintain tolerance towards self-antigens as well as non-inherited maternal antigens.

Maternal-fetal in vivo transfer of [13C]docosahexaenoic and other fatty acids across the human placenta 12 h after maternal oral intake.

BACKGROUND: Fetal growth and development require n-3 (omega-3) long-chain polyunsaturated fatty acids, but mechanisms for their placental transfer are not well understood. OBJECTIVE: We assessed distribution and human placental transfer of (13)C-labeled fatty acids (FAs) 12 h after oral application. DESIGN: Eleven pregnant women received 0.5 mg [(13)C]palmitic acid ((13)C-PA; 16:0), 0.5 mg [(13)C]oleic acid ((13)C-OA; 18:1n-9), 0.5 mg [(13)C]linoleic acid ((13)C-LA; 18:2n-6), and 0.1 mg [(13)C]docosahexaenoic acid ((13)C-DHA; 22:6n-3) per kilogram of body weight orally 12 h before elective cesarean section. Maternal blood samples were collected before tracer intake (-12 h) and at -3, -2, -1, 0, and +1 h relative to the time of cesarean section. At birth, venous cord blood and placental tissue were collected, and FA concentrations in individual lipid fractions and their tracer content (atom percent excess values) were determined. RESULTS: Relatively stable tracer enrichment was achieved in maternal lipid fractions 12 h after tracer administration. In maternal plasma, most (13)C-PA and (13)C-OA were found in triglycerides, whereas (13)C-LA and (13)C-DHA were found mainly in plasma phospholipids and triglycerides. In placental tissue, (13)C-FAs were mainly found in phospholipids, which comprise 80% of placental tissue lipids. Placenta-maternal plasma ratios and fetal-maternal plasma ratios for (13)C-DHA were significantly higher than those for any other FA. CONCLUSIONS: Twelve hours after oral application of (13)C-labeled FAs, relatively stable tracer enrichment was achieved. We found a significantly higher ratio of (13)C-DHA concentrations in cord plasma than in maternal plasma, which was higher than that for the other studied FAs. (13)C-DHA is predominantly esterified into phospholipids and triglycerides in maternal plasma, which may facilitate its placental uptake and transfer.