160 - IUGR Induces Sex-Divergent Changes in PC-DHA, LPC-DHA, and Mfsd2a in the Rat Lung

Poster Number: 160
Publication Number: 160.311

Adrienne Cohen, University of Utah, Salt Lake City, UT, United States; Ryan Gage, University of Utah School of Medicine, Springville, UT, United States; Trey Benally, The University of New Mexico, Albuquerque, NM, United States; Haimei Wang, university of utah, Holladay, UT, United States; James Cox, University of Utah School of Medicine, Salt Lake City, UT, United States; John A. Maschek, University of Utah School of Medicine, Salt Lake City, UT, United States; lisa Joss-Moore, UNIVERSITY OF UTAH, Salt Lake City, UT, United States

Background: Human neonates rely on adequate docosahexaenoic acid (DHA) for appropriate lung development. Low circulating neonatal DHA is associated with the development of bronchopulmonary dysplasia (BPD). BPD is characterized by impaired lung development. Both BPD and impaired fetal DHA acquisition are exacerbated by intrauterine growth restriction (IUGR). Lung uptake of DHA from the neonatal circulation is primarily as phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) DHA. Cellular uptake of PC-DHA and LPC-DHA is facilitated by the omega-3 fatty acid transporter MFSD2A. In a rat model, we previously demonstrated that IUGR 1) impairs lung development, and 2) decreases circulating DHA in male, but not female, rat pups. However, the effect of IUGR on serum and lung PC-DHA and LPC-DHA and lung Mfsd2a mRNA levels is currently unknown.

Objective: To test the hypothesis that IUGR causes sex-divergent changes in serum and lung PC-DHA and LPC-DHA and lung Mfsd2a mRNA in the rat.

Design/Methods: IUGR was induced by bilateral uterine artery ligation in Sprague Dawley rats. Control dams received anesthesia only. Rat pups were euthanized at term c-section delivery, and serum and lung tissue collected. Male and female rats were treated as separate groups. PC-DHA and LPC-DHA were measured using GC/MS. Mfsd2a mRNA was measured using real-time RT PCR. Statistical differences were determined using 1-way ANOVA with post hoc unpaired t-test.

Results: Results are IUGR as % of sex-matched control±SD, *P < .05. In serum, IUGR decreased PC-DHA (64±7%*) and LPC-DHA (65±30%*) in male rat pups, with no change in female rat pups. Within the lung, IUGR also decreased PC-DHA (85±8%*) and LPC-DHA (79±23%*) in males, with no change in females. Conversely, IUGR increased lung Mfsd2a mRNA in female but not male rat lungs (159±76%*).Conclusion(s): IUGR causes sex-divergent changes in serum and lung PC-DHA, LPC-DHA, and lung Mfsd2a mRNA. In male rats, IUGR reduces serum and lung PC-DHA and LPC-DHA. While in female rats, IUGR increases lung Mfsd2a mRNA. We speculate that reduced serum and lung DHA in IUGR male rats may contribute to previously observed impaired lung development. We further speculate that upregulation of Mfsd2a mRNA in female rat lungs may be a compensatory mechanism to maximize lung DHA uptake in IUGR females.