Sex-Dependent Regulation of Placental Oleic Acid and Palmitic Acid Metabolism by Maternal Glycemia and Associations with Birthweight

Sex-Dependent Regulation of Placental Oleic Acid and Palmitic Acid Metabolism by Maternal Glycemia and Associations with Birthweight

International Journal of Molecular Sciences

10.3390/ijms23158685

https://doi.org/10.3390/ijms23158685

Oliver C. Watkins, Hannah E. J. Yong, Tania Ken Lin Mah, Victoria K. B. Cracknell-Hazra, Reshma Appukuttan Pillai, Preben Selvam, Neha Sharma, Amaury Cazenave-Gassiot, Anne K. Bendt, Keith M. Godfrey, Rohan M. Lewis, Markus R. Wenk, Shiao-Yng Chan

lipid metabolism, maternal glycaemia, Fetal sex, placenta, birthweight

05 August 2022

Watkins, O. C., Yong, H. E. J., Mah, T. K. L., Cracknell-Hazra, V. K. B., Pillai, R. A., Selvam, P., Sharma, N., Cazenave-Gassiot, A., Bendt, A. K., Godfrey, K. M., Lewis, R. M., Wenk, M. R., & Chan, S.-Y. (2022). Sex-Dependent Regulation of Placental Oleic Acid and Palmitic Acid Metabolism by Maternal Glycemia and Associations with Birthweight. International Journal of Molecular Sciences, 23(15), 8685. https://doi.org/10.3390/ijms23158685

Pregnancy complications such as maternal hyperglycemia increase perinatal mortality and morbidity, but risks are higher in males than in females. We hypothesized that fetal sex-dependent differences in placental palmitic-acid (PA) and oleic-acid (OA) metabolism influence such risks. Placental explants (n = 22) were incubated with isotope-labeled fatty acids (13C-PA or 13C-OA) for 24 or 48 h and the production of forty-seven 13C-PA lipids and thirty-seven 13C-OA lipids quantified by LCMS. Linear regression was used to investigate associations between maternal glycemia, BMI and fetal sex with 13C lipids, and between 13C lipids and birthweight centile. Placental explants from females showed greater incorporation of 13C-OA and 13C-PA into almost all lipids compared to males. Fetal sex also influenced relationships with maternal glycemia, with many 13C-OA and 13C-PA acylcarnitines, 13C-PA-diacylglycerols and 13C-PA phospholipids positively associated with glycemia in females but not in males. In contrast, several 13C-OA triacylglycerols and 13C-OA phospholipids were negatively associated with glycemia in males but not in females. Birthweight centile in females was positively associated with six 13C-PA and three 13C-OA lipids (mainly acylcarnitines) and was negatively associated with eight 13C-OA lipids, while males showed few associations. Fetal sex thus influences placental lipid metabolism and could be a key modulator of the impact of maternal metabolic health on perinatal outcomes, potentially contributing toward sex-specific adaptions in which females prioritize survival.

Attribution 4.0 International (CC BY 4.0)

This research is supported by a Clinician Scientist Award awarded to S.-Y.C. from the Singapore National Medical Research Council (NMRC/CSA-INV/0010/2016, MOH-CSAINV19nov- 0002), by the National University of Singapore, National University Health System Singapore, and the Singapore Institute for Clinical Sciences A*STAR. The Singapore Lipidomics Incubator receives funding from the Life Sciences Institute, the National University of Singapore Yong Loo Lin School of Medicine, the National Research Foundation Investigatorship (grant number NRFI2015-05), and A*STAR (IAF-ICP I1901E0040). K.M.G. is supported by the UK Medical Research Council (MC_UU_12011/4), the National Institute for Health Research (NIHR Senior Investigator (NF-SI-0515-10042) and NIHR Southampton Biomedical Research Centre (IS-BRC-1215-20004)), the European Union (Erasmus+ Programme ImpENSA 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP).

This research / project is supported by the Agency for Science, Technology and Research - Industry Alignment Fund – Industry Collaboration Projects
Grant Reference no. : I1901E0040

https://oar.a-star.edu.sg/communities-collections/articles/21989

1422-0067

Institute for Human Development and Potential

https://doi.org/10.3390/ijms23158685