The supplementation of a high dose of fish oil during pregnancy and lactation led to an elevation in Mfsd2a expression without any changes in docosahexaenoic acid levels in the retina of healthy 2-month-old mouse offspring

Irena Jovanovic Macura; Ivana Djuricic; Tamara Major; Desanka Milanovic; Sladjana Sobajic; Selma Kanazir; Sanja Ivkovic

doi:10.3389/fnut.2023.1330414

The supplementation of a high dose of fish oil during pregnancy and lactation led to an elevation in Mfsd2a expression without any changes in docosahexaenoic acid levels in the retina of healthy 2-month-old mouse offspring

Front Nutr. 2024 Jan 24:10:1330414. doi: 10.3389/fnut.2023.1330414. eCollection 2023.

Authors

Irena Jovanovic Macura¹, Ivana Djuricic², Tamara Major², Desanka Milanovic¹, Sladjana Sobajic², Selma Kanazir¹, Sanja Ivkovic³

Affiliations

¹ Institute for Biological Research "Sinisa Stankovic", National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia.
² Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
³ Vinca Institute for Nuclear Sciences, National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia.

Abstract

Introduction: During fetal development, the proper development of neural and visual systems relies on the maternal supplementation of omega-3 fatty acids through placental transfer. Pregnant women are strongly advised to augment their diet with additional sources of omega-3, such as fish oil (FO). This supplementation has been linked to a reduced risk of preterm birth, pre-eclampsia, and perinatal depression. Recently, higher doses of omega-3 supplementation have been recommended for pregnant women. Considering that omega-3 fatty acids, particularly docosahexaenoic acid (DHA), play a crucial role in maintaining the delicate homeostasis required for the proper functioning of the retina and photoreceptors the effects of high-dose fish oil (FO) supplementation during pregnancy and lactation on the retina and retinal pigmented epithelium (RPE) in healthy offspring warrant better understanding.

Methods: The fatty acid content and the changes in the expression of the genes regulating cholesterol homeostasis and DHA transport in the retina and RPE were evaluated following the high-dose FO supplementation.

Results: Our study demonstrated that despite the high-dose FO treatment during pregnancy and lactation, the rigorous DHA homeostasis in the retina and RPE of the two-month-old offspring remained balanced. Another significant finding of this study is the increase in the expression levels of major facilitator superfamily domain-containing protein (Mfsd2a), a primary DHA transporter. Mfsd2a also serves as a major regulator of transcytosis during development, and a reduction in Mfsd2a levels poses a major risk for the development of leaky blood vessels.

Conclusion: Impairment of the blood-retinal barrier (BRB) is associated with the development of numerous ocular diseases, and a better understanding of how to manipulate transcytosis in the BRB during development can enhance drug delivery through the BRB or contribute to the repair of central nervous system (CNS) barriers.

Keywords: DHA; EPA; Mfsd2a; RPE; fish oil; lactation; pregnancy; retina.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia (contract nos. 451-03-9/2021-14/200007, 451-03-9/2021-14/200017, and 451-03-47/2023-01/200161).