Altered blood plasma and follicular fluid lipid profiles predict alterations in cell signaling, metabolism, and immune function in cows with androgen excess

Authors: NEILSON, MEGAN - University Of Nebraska; SPURI GOMES, RENATA - University Of Nebraska; ROMEREIM, SARAH - University Of Nebraska; SUMMERS, ADAM - New Mexico State University; ABEDAL-MAJED, MOHAMED - University Of Nebraska; TENLEY, SARAH - University Of Nebraska; KURZ, SCOTT - University Of Nebraska; BERGMAN, JEFF - University Of Nebraska; Cushman, Robert - Bob; DAVIS, JOHN - Nebraska Medical Center; WOOD, JENNIFER - University Of Nebraska; CUPP, ANDREA - University Of Nebraska

Submitted to: Society for the Study of Reproduction Annual Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 5/1/2018
Publication Date: 7/2/2018
Citation: Neilson, M.A., Spuri Gomes, R., Romereim, S.M., Summers, A.F., Abedal-Majed, M.A., Tenley, S.C., Kurz, S.G., Bergman, J.W., Cushman, R.A., Davis, J.S., Wood, J.R., Cupp, A.S. 2018. Altered blood plasma and follicular fluid lipid profiles predict alterations in cell signaling, metabolism, and immune function in cows with androgen excess [abstract]. Society for the Study of Reproduction Annual Meeting. Abstract Program p. 323-324. Available: https://www.ssr.org/sites/ssr.org/files/2018_annual_meeting_abstracts_updated.pdf

Interpretive Summary:

Technical Abstract: We have previously described cows in the UNL physiology herd with excess androstenedione (A4; High A4 > 40 ng/ml; control < 20 ng/ml) in follicular fluid of dominant follicles, reduced Sex Hormone Binding Globulin, alterations in liver hormone metabolism, and arrested follicular development leading to anovulation and reduced fertility. Our objective was to determine potential differences in blood plasma and follicular fluid lipid profiles in High A4 cows and controls. Our hypothesis was that altered lipid profiles in plasma and follicular fluid in High A4 cows compared to controls would identify metabolic, signal transduction or biological process contributing to altered follicular development resulting in anovulation. Blood plasma samples were collected at day 7 and 15 of a non-stimulated cycle where cows were synchronized to initiate a new follicular wave. Blood plasma and follicular fluid was collected at ovariectomy after FSH stimulation (20ng/ml every 12 hours ending with a Prostaglandin F2alpha (PG) injection at last FSH injection; ovariectomy 36-42 hours afterlast PG). A total of 863 lipid compounds were identified in the follicular fluid and plasma samples via HPLC mass spectrometry but only 115 of the lipid compounds were annotated, so some lipids are designated by compound number. The top 4 lipid compounds per sample were chosen in High A4 compared to control cows using the Random Forest Algorithm for each sample. At day 7 of the non-stimulated cycle, lysophosphatidylethanolamine 22:4 (LysoPE(22:4)), which induces the MAPK signal transduction pathway, mediating cell growth and differentiation and C760 was significantly reduced in plasma from High A4 cows (P<0.05). On day 15 of the non-stimulated cycle, blood plasma had greater concentrations of C272, lysophosphatidylcholine (LPC) 22:4 (LPC( (22:4)) and lysophosphatidylcholine 22:5 (LPC(22:5)) in the High A4 cows (P<0.05). The LPCs interact with G protein-coupled receptors, which distinguish them as novel ligands of orphan receptors, and are involved in carbohydrate and lipid metabolism suggestive of increased metabolic rate in High A4 cows. The follicular fluid collected at ovariectomy in the FSH-stimulated cycle was different across all 4 lipids, with C825, C600 and 1-(1Z-octadecenyl)-2-oleoyl-sn-glycero-3-phosphocholine (Plg-SOPC) being increased and Sphingomyelin (SM(d18:0/16:1(9Z))) decreased in High A4 cows compared to controls (P<0.05). Not much is known about Plg-SOPC; however, it is produced in response to oxidative stress. Sphingomylin helps form lipid rafts regulating signal transduction thus a reduction may inhibit these processes. Taken together, these data indicate that altered lipids in the blood plasma of High A4 cows may increase MAPK and G-protein receptor signaling to increase metabolic rate while lipids in the follicular fluid decrease oxidative stress and inhibit G-protein receptor signaling compared to controls. Thus, variations in lipid profiles of High A4 and control cows suggests potential differences in metabolic, immune and cell signaling of the High A4 cows which may contribute to their follicular arrest, anovulation and infertility. This research was funded through USDA grant 2013-67015-20965.