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

Year: 2022

Type: article

Abstract: 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.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms23158685

Authors: 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

Institutions: National University of Singapore, Agency for Science, Technology and Research, Singapore Institute for Clinical Sciences, University Hospital Southampton NHS Foundation Trust, NIHR Southampton Biomedical Research Centre, University of Southampton, Life Sciences Institute, MRC Lifecourse Epidemiology Unit

Language: English

Topic: Gestational Diabetes Research and Management

Subfield: Obstetrics and Gynecology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,408

Funders: Danone, National Institute for Health and Care Research, European Commission, National Research Foundation, Agency for Science, Technology and Research, National University of Singapore, National Institute for Health Research Southampton Biomedical Research Centre, Medical Research Council

OpenAlex ID: W4289833814