A closer look at the placental lipidome reveals molecular differences between active and inactive pregnancies, offering new clues about how maternal movement may shape the environment supporting fetal development.
Study: Exploring the placental lipidome in physically active versus inactive pregnancies. Image Credit: Inside Creative House / Shutterstock.com
Routine exercise during pregnancy may confer sustained health benefits, as women who stay active during pregnancy have a lower risk of several pregnancy-related complications. Physical activity (PA) has also been linked to a lower risk of some adverse health outcomes in the offspring; however, the biological mechanisms behind these associations remain unclear.
A recent study published in the Journal of Applied Physiology suggests that PA during pregnancy may influence placental lipid metabolism.
Tracking activity and placental lipids
In this study, researchers examined lipid changes in the placenta of physically active and inactive individuals. Researchers recruited participants across Ottawa and Baton Rouge from the PLACENTA and Expecting Success trials.
The Canadian Institutes for Health Research (CIHR) funded the former, while the latter received funding from the National Institutes of Health (NIH). In both projects, participants were aged 18 to 40 years and had singleton pregnancies. Participants with pre-existing diabetes, untreated thyroid disease, or medicated hypertension were excluded.
A total of 36 placental samples collected at term from women with uncomplicated pregnancies underwent lipidomic analyses using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The team also performed Western blot assays to analyze the expression of the major facilitator superfamily domain-containing 2a (MFSD2a) protein, which is associated with DHA transfer and uptake at the placenta and the blood-brain barrier (BBB).
Participants in both trials wore accelerometers to objectively measure PA, although the studies used different devices and wear protocols. For this analysis, activity status was determined from third-trimester accelerometer data, as these measurements were closest to placental tissue collection at term.
In the trial, participants were randomized to no intervention, in-person intervention, or a remote intervention; the intervention arms received dietary and exercise advice along with behavior-modification counseling. Dietary intake was assessed using the automated self-administered dietary assessment (ASA24) tool and participant diet recalls.
Participants were classified as active if third-trimester accelerometer data indicated that they met the recommended 150 minutes of moderate PA per week. Principal component analysis (PCA) showed modest separation in overall lipid profiles between the groups, while supervised partial least squares discriminant analysis (PLS-DA) further distinguished active from inactive participants.
Pathway analysis identified a lipid pathway enriched in active individuals. Area under the receiver-operating characteristic curve (AUROC) values were used to assess individual lipids as potential biomarkers of PA status.
Physical activity leaves a distinct placental lipid signature.
The sample population comprised 17 inactive and 19 active individuals. The only significant difference between the active and inactive groups was third-trimester moderate-to-vigorous PA (34.8 vs. 10.8 minutes per day). In total, the team annotated 192 lipids, 39 of which differed significantly after adjustment for multiple comparisons. After applying an additional fold-change threshold, 34 lipids met both criteria.
Among the 17 identified DHA-containing lipid species, seven met both the statistical and fold-change thresholds and were more abundant in placentas from active participants. The researchers suggested this pattern could indicate greater DHA availability for fetal brain and retinal development, but they did not directly measure fetal DHA delivery. This is especially relevant since the fetus cannot synthesize DHA and relies on transfer from maternal circulation. Lower DHA levels have been associated with gestational diabetes and preeclampsia in pregnant women and adverse long-term neural and cognitive outcomes in the offspring.
Five lipid species, TG 16:0/18:0/18:1, TG 18:0/18:1/18:1, PE 18:1/22:5, cholesteryl palmitate, and PC 16:0/16:2, perfectly distinguished the active and inactive groups within this study sample. Their potential use as PA biomarkers will require validation in larger, independent populations. The phosphatidylserine decarboxylase (PISD) pathway was also enriched in the active group.
MFSD2a expression did not differ significantly between inactive and active participants. After accounting for PA status and gestational weight gain, higher MFSD2a expression was associated with a lower infant weight-to-length ratio. Sensitivity analyses adjusting for study site, weeks of pregnancy at delivery, and fetal sex yielded similar findings.
The researchers caution that the exploratory study was small and measured placental lipids only at term; therefore, these findings cannot show how lipid profiles change across pregnancy. Without cord blood samples, the study could not establish whether differences in placental lipids corresponded to altered lipid delivery to the fetus. Accelerometers measured activity volume and intensity but could not distinguish specific activities such as muscle-strengthening exercise.
What placental lipids could reveal about activity in pregnancy?
The findings indicate differences in placental lipid profiles between physically inactive and active women during pregnancy, suggesting that PA may influence lipid-related functions such as fetal nutrient transport and energy metabolism. If confirmed in larger studies, some of the identified lipids could serve as PA biomarkers.
In the future, researchers could include cord blood lipid analysis and explore associations of maternal adiposity and PA (including muscle-strengthening exercises) with fetal growth outcomes. These studies could clarify the biological significance of these lipid differences and how they relate to pregnancy and fetal outcomes.
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