Abstract
Polycystic ovarian syndrome (PCOS) symptoms include excessive body or facial hair, irregular periods, reduced fertility, and reoccurring pregnancy loss. Hyperandrogenism and chronic inflammation are hallmarks of PCOS, which is diagnosed by analysing steroid hormones in the blood. Studies suggest that bioactive lipids are contributing to chronic inflammation. To research PCOS, animal models, such as letrozole- and dihydrotestosterone-treated rats, are used. They display similar ovarian and metabolic characteristics, although plasma lipid profiles have not been determined. Therefore, in order to validate the use of these models for PCOS, we have optimised a mass spectrometry based targeted lipidomics workflow which increases the sensitivity of measuring these lipids in rat plasma. Our analysis shows that letrozole caused a significant elevation of 5α-androstene-3,17-dione and testosterone. Dihydrotestosterone treatment resulted in increased dehydroepiandrosterone-sulphate and allopregnanolone but a reduction in testosterone, progesterone, pregnenolone, and D-sphingosine. In both models 25-hydroxycholesterol and leukotriene C4 were significantly diminished and 4-cholesten-3-one was significantly increased, and these particular metabolites are not known to be changed in human PCOS. These results suggest that the plasma lipids of these rodent models have some changes akin to human PCOS and other changes that are not.
Competing Interest Statement
The authors have declared no competing interest.
Abbreviations
- γ-LA
- γ-linolenic acid
- 3αAP/AP
- 3α-Hydroxy-5α-Pregnane-20-one
- 3β-HSD
- 3β-hydroxysteroid dehydrogenase
- 5-HPETE
- 5-hydroperoxyeicosatetraenoic acid
- A4
- 4-Androstene-3,17-dione
- Aα5
- 5α-Androstane-3,17-dione
- AA
- Arachidonic acid
- AKR1C1/2/4
- 3α-hydroxysteroid dehydrogenase class 1/2/4
- ALOX5
- Arachidonate 5-lipoxygenase
- ASAH1/2/ ACER1/2
- neutral ceramidase
- AUC
- Area under the curve
- CE
- collisional energy
- CH25H
- Cholesterol 25-hydroxylase b
- choD
- cholesterol oxidase
- COX-2
- Cyclooxygenase 2
- CV
- coefficient of variation
- CYP11
- Steroid 11β-monooxygenase
- CYP11A
- Cytochrome P450 family 11 subfamily A
- CYP11B1
- Steroid 11β-monooxygenase
- CYP142
- cholest-4-en-3-one 26-monooxygenase
- CYP17A
- Steroid 17α-monooxygenase
- CYP19A1
- Cytochrome P450 aromatase
- CYP21A
- Steroid 21-monooxygenase
- CYP2E1
- Cytochrome P450 family 2 subfamily E1
- DHCR7
- 7-Dehydrocholesterol reductase
- DHEA
- Dehydroepiandrosterone
- DHEA-S
- Dehydroepiandrosterone-sulphate
- DHT/5α-DHT
- 5α-Dihydrotestosterone
- DHT-C
- Dihydrotestosterone control
- diOHchol
- Dihydrocholesterol
- D-Sph/Sph
- D-Sphingosine
- dMRM
- Dynamic multiple reaction monitoring
- E1
- Estrone
- E1.1.1.51
- 3 (or 17) β-Hydroxysteroid dehydrogenase
- E2
- β-Estradiol
- E3
- Estriol
- E5.3.3.1
- steroid Δ-isomerase
- GABAA
- γ-Aminobutyric acid type A
- GALC
- Galactosylceramidase
- GBA
- non-lysosomal glucosylceramidase
- GGT1/5
- leukotriene-C4 hydrolase
- GPX4
- phospholipid-hydroperoxide glutathione peroxidase
- H2O
- Water
- HSD3B
- 3β-Hydroxysteroid dehydrogenase
- HSD11B1/2
- Hydroxysteroid 11-β-dehydrogenase isozyme 1/2
- HSD17B1/2
- 17β-Estradiol 17-dehydrogenase 1/2
- HSD17B3
- Testosterone 17β-dehydrogenase (NADP+)
- HSD17B11
- Hydroxysteroid 17β-dehydrogenase 11
- IM
- ion mobility
- IPA
- Isopropanol
- LC-dMRM-MS
- Liquid chromatography-dynamic multiple reaction monitoring-mass spectrometry
- LET
- Letrozole
- LET-C
- Letrozole control
- LLOD
- Lower limit of detection
- LLOQ
- Lower limit of quantification
- LTA4
- Leukotriene A4
- LTA4H
- Leukotriene A4 hydrolase
- LTB4
- Leukotriene B4
- LTC4
- Leukotriene C4
- LTC4S
- Leukotriene C4 synthase
- MAGL
- Monoacylglycerol lipase
- MeOH
- Methanol
- MRM
- Multiple reaction monitoring
- MTBE
- Methyl tert-butyl ether
- o.c.
- on-column
- PCOS
- Polycystic ovarian syndrome
- PLGA
- poly-lactic-glycolic acid
- PLPP1/2/3
- Phosphatidate phosphatase 1/2/3
- Preg
- Pregnenolone
- Prog
- Progesterone
- PTGR1/2
- Prostaglandin reductase 1/2
- PTGS1/2
- prostaglandin-endoperoxide synthase 1
- QC
- Quality control
- Qual
- qualifier ion
- Quant
- Quantifier ion
- RF
- Response factor
- S/N
- Signal-to-noise ratio
- SGMS1/2
- sphingomyelin synthase
- SGPP1/2
- Sphingosine-1-phosphate phosphatase 1/2
- SMPD1-4/ENPP7
- ectonucleotide pyrophosphatase/phosphodiesterase family member 7
- SPHK1/2
- Sphingosine kinase 1/2
- SRD5A1
- 3-Oxo-5α-steroid 4-dehydrogenase 1
- STD
- standard
- STS
- Stearyl-sulfatase
- SULT1E1
- estrone sulfotransferase
- SULT2B
- Sulfotransferase family 2B member 1
- TesI
- 3-Oxo-5α-steroid 4-dehydrogenase
- TIR
- Transition Ion Ratios
- UGT
- uridine diphosphoglucuronosyltransferase
- UGT8
- Ceramide galactosyltransferase
- ZADH2
- Zinc binding alcohol dehydrogenase domain containing 2.
