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Topical Area: Energy and Macronutrient Metabolism

Energy and Macronutrient Metabolism (Poster Session)

(P16-012-23) The Role of Omega-3 Derived Specialized Pro-Resolving Mediators in the Mitochondria of the Hypertensive Placenta

Sunday, July 23, 2023
12:45 PM – 1:45 PM ET
Location: Poster Board 176
Disclosure(s):
Taija M. Hahka, MS, BS: No relevant financial relationship(s) with ineligible companies to disclose.
Rebecca Slotkowski, B.S.: No relevant financial relationship(s) with ineligible companies to disclose.
Anum Akbar, MBBS: No relevant financial relationship(s) with ineligible companies to disclose.


Objectives: Hypertensive Disorders of Pregnancy (HDP) is characterized by poor placental trophoblast invasion and a maternal systemic inflammatory response. Inflammation results in mitochondrial dysfunction or uncontrolled mitochondrial replication, promoting placental stiffness in preeclampsia. Mitochondrial transcription factor A (TFAM), a controller of mitochondrial DNA replication, is a key player. Omega-3 (n-3) fatty acid-derived specialized pro-resolving mediators (SPMs) promote anti-inflammatory and pro-repair processes; however, the mechanism between SPMs regulating inflammation and mitochondrial dysfunction during HDP is unclear.

We hypothesize that SPMs mitigate pro-inflammatory cytokine (TNFa) and mitochondrial dysfunction in the placental trophoblasts by modulation of TFAM and oxygen consumption rates in artificial tissue stiffnesses.

Methods: Human normotensive and hypertensive placenta samples underwent RNA-seq to obtain relative mRNA expression (n=4 per group). Human-derived trophoblast cells were subjected to pro-inflammatory cytokine (TNFa, 10 ng/mL) or Bio-Engineered Adhesive Siloxane Substrate with Tunable Stiffness (BEASTS) to mimic in vivo placental stiffness for 8, 25, and 55 kPa. SPM, resolvin D2 (RvD2, 100nM) was applied to mitigate inflammation and mitochondrial dysfunction. RTqPCR and WB was used to measure TFAM mRNA and protein levels, and Seahorse® was used to measure OCR (n=3-4 per group). One-way ANOVA or student t-test was performed; mean ± SD.

Results: Our RNA-seq data showed that TFAM is increased in hypertensive human placenta compared to normotensive placenta (p=0.0036). Trophoblasts subjected to TNFa demonstrated increased TFAM expression levels; treatments with RvD2 mitigated this (p=0.0258). Trophoblasts exposed to 55kPa and treated with RvD2 decreased TFAM expression by 2.5-fold (p=0.0021). Seahorse® measurements of trophoblasts exposed to TNFa+RvD2 demonstrated trends of improved maximal respiratory rate ranges (TNFa:48-194 vs. TNFa+RvD2:97-231; pmol/min/mg/ml) and ATP mean production (p=0.0697).

Conclusions: RvD2 exhibits a protective role through modulation of TFAM in the mitochondria of human-derived trophoblasts during inflammatory insult or tissue stiffness.

Funding Sources: Trainee CHRI-mini grant, CHRI and Hobel Grant, John and Patty Sparks Chair Funding