Telomere Length and Telomerase Activity of Granulosa Cells and Follicular Fluid in Women Undergoing In Vitro Fertilization
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients, Pretreatment Investigation and Superovulation Protocols
2.2. Collection of Follicular Fluid and Granulosa Cells
2.3. Fertilization Methods
2.4. Laboratory Measurements
2.5. Telomere Length and Telomerase Activity Analysis
2.5.1. DNA Isolation
2.5.2. Telomere Length
2.5.3. Telomerase Activity
2.6. Ethical Approval and Consent to Participate
2.7. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
6. Study Limitations
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | Mean Value | Standard Deviation |
---|---|---|
Age (years) | 35.11 | 4.89 |
Body Mass Index (kg/m2) | 26.08 | 6.45 |
No. of previously performed IVF cycles | 2.1 | 1.08 |
Infertility diagnosis (%) | ||
Male factor (n = 52) | 50.98 | |
Tubal occlusion (n = 31) | 30.39 | |
Endometriosis (n = 14) | 13.73 | |
Advanced maternal age (n = 10) | 9.80 | |
Unexplained (n = 10) | 9.80 | |
Other female factors (n = 7) | 6.86 | |
Serum estradiol (pmol/L) | 1749 | 1745 |
Total dose of gonadotropin (IU) | 2601 | 834 |
Protocol of controlled ovarian stimulation (%) | ||
Antagonist | 57.84 | |
Short agonist | 12.75 | |
Long agonist | 29.41 | |
No. of retrieved oocytes | 10.03 | 6.34 |
Metaphase II oocytes—matured | 6.52 | 4.93 |
Metaphase I oocytes—immature | 1.47 | 1.58 |
Oocytes with germinal vesicle—immature | 1.2 | 1.76 |
Fertilization method (%) | ||
Intracytoplasmatic Sperm Injection—ICSI | 100 | |
Conventional IVF + ICSI | 8.91 | |
Fertilized oocytes with two pronuclei—2PN cell | 3.35 | 3.16 |
Grade 1 embryos at day 3 (cleavage stage embryo) | 3.42 | 2.71 |
Grade 1 embryos at day 5 (blastocyst) | 2.23 | 2.3 |
Chemical pregnancies | 27 | |
hCG mean value in case of chemical pregnancies (IU) | 1283 | 1010 |
No. of subjects (n) | 102 |
Reference genomic DNA sample | 1 μL |
Primer stock solution (Telomere or SCR) | 2 μL |
2x GoldNStart TaqGreen qPCR master mix (Cat #MB6018a-1) | 10 μL |
Nuclease-free H2O (Cat #8918c) | 7 μL |
Total volume | 20 μL |
Genomic DNA template | 1 μL |
Primer stock solution (Telomere or SCR) | 2 μL |
2x GoldNStart TaqGreen qPCR master mix (Cat #MB6018a-1) | 10 μL |
Nuclease-free H2O (Cat #8918c) | variable |
Total volume | 20 μL |
Step | Temperature | Time | Number of Cycles |
---|---|---|---|
Initial denaturation | 95 °C | 10 min | 1 |
Denaturation | 95 °C | 20 s | 32 |
Annealing | 52 °C | 20 s | |
Extension | 72 °C | 45 s | |
Data acquisition | Plate read | ||
Melting curve analysis | 1 | ||
Hold | 20 °C | Indefinite | 1 |
Cell lysate sample or cell lysis buffer | 0.5 μL |
5xTelomerase reaction buffer | 4 μL |
Nuclease-free H2O (Cat #8928d) | 15.5 μL |
Total volume | 20 μL |
Post-telomerase reaction sample or H2O | 1 μL |
Primer stock solution (TPS) | 2 μL |
2x qPCR master mix | 10 μL |
Nuclease-free H2O (Cat #8928d) | 7 μL |
Total volume | 20 μL |
Step | Temperature | Time | Number of Cycles |
---|---|---|---|
Initial denaturation | 95 °C | 10 min | 1 |
Denaturation | 95 °C | 20 s | 40 |
Annealing | 52 °C | 20 s | |
Extension | 72 °C | 45 s | |
Data acquisition | Plate read | ||
Melting curve analysis | 1 | ||
Hold | 20 °C | Indefinite | 1 |
Parameters | Granulosa Cell | Follicular Fluid | p-Value |
---|---|---|---|
Total Patients | |||
Telomere length (bp) (n = 89) | 11.7 (0–69.6) | 9.9 (0–48.3) | 0.991 |
Telomerase activity (no dimension) (n = 90) | 0.0007 (0.0007–0.2) | 0.000001 (0.0000001–0.005) | <0.001 |
8-OHdG level/retrieved oocyte (ng/mL) (n = 72) | 0.2 (0.04–1.7) | 2.2 (0.6–12.05) | <0.001 |
Pregnant patients | |||
Telomere length (bp) (n = 24) | 12.9 (0–69.6) | 7.0 (1–28.1) | 0.136 |
Telomerase activity (no dimension) (n = 26) | 0.0009 (0.0007–0.03) | 0.000001 (0.0000001–0.005) | <0.001 |
8-OHdG level/retrieved oocyte (ng/mL) (n = 22) | 0.2 (0.04–0.6) | 1.7 (0.7–12.1) | <0.001 |
Non-pregnant patients | |||
Telomere length (bp) (n = 65) | 10.4 (0–37.1) | 10.5 (0–48.3) | 0.325 |
Telomerase activity (no dimension) (n = 64) | 0.0007 (0.0007–0.2) | 0.000001 (0.0000001–0.003) | <0.001 |
8-OHdG level/retrieved oocyte (ng/mL) (n = 50) | 0.3 (0.06–1.7) | 2.6 (0.6–10.3) | <0.001 |
Parameters | Non Pregnant | Pregnant | p-Value |
---|---|---|---|
Telomere length in granulosa cell (bp) | |||
Under median | 38 (54.3%) | 10 (38.5%) | 0.168 |
Equal to or higher than median | 32 (45.7%) | 16 (61.5%) | |
Total | 70 (100%) | 26 (100%) | |
Telomere length in follicular fluid (bp) | |||
Under median | 31 (45.6%) | 16 (64.0%) | 0.115 |
Equal to or higher than median | 37 (54.4%) | 9 (36.0%) | |
Total | 68 (100%) | 27 (100%) | |
Telomerase activity in granulosa cell (no dimension) | |||
Under median | 34 (53.1%) | 13 (50.0%) | 0.788 |
Equal to or higher than median | 30 (46.9%) | 13 (50.0%) | |
Total | 64 (100%) | 26 (100%) | |
Telomerase activity in follicular fluid (no dimension) | |||
Under median | 30 (48.3%) | 16 (62.5%) | 0.207 |
Equal to or higher than median | 34 (51.6%) | 10 (37.5%) | |
Total | 64 (100%) | 26 (100%) | |
8-OHdG/oocyte in granulosa cell (ng/mL) | |||
Under median | 22 (42.0%) | 11 (50.0%) | 0.638 |
Equal to or higher than median | 28 (58.0%) | 11 (50.0%) | |
Total | 50 (100%) | 22 (100%) | |
8-OHdG/oocyte in follicular fluid (ng/mL) | |||
Under median | 21 (42.0%) | 15 (68.2%) | 0.041 |
Equal to or higher than median | 29 (58.0%) | 7 (31.8%) | |
Total | 50 (100%) | 22 (100%) |
Parameters | No. of Retrieved Oocytes | Immature Oocyte | MII Oocyte | 2PN Cell (Day 1) | Cleavage Stage Embryo (Day 3) | Blastocyst (Day 5) | ||
---|---|---|---|---|---|---|---|---|
GV Oocyte | MI Oocyte | |||||||
Telomere length | GC | 0.09 | 0.05 | 0.01 | 0.07 | −0.02 | −0.02 | 0.01 |
FF | −0.03 | 0.02 | 0.06 | −0.04 | −0.05 | −0.02 | −0.14 | |
Telomerase activity | GC | 0.19 | 0.04 | 0.21 * | 0.09 | 0.04 | −0.04 | 0.01 |
FF | −0.19 | −0.01 | −0.06 | −0.19 | −0.05 | 0.05 | −0.07 | |
8-OHdG/no. of retrieved oocytes | GC | −0.49 ** | −0.20 | −0.11 | −0.36 ** | −0.21 | −0.10 | −0.11 |
FF | −0.65 ** | −0.20 | −0.19 | −0.64 ** | −0.34 ** | 0.06 | −0.32 ** |
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Péntek, S.; Várnagy, Á.; Farkas, B.; Mauchart, P.; Gödöny, K.; Varjas, T.; Kőszegi, T.; Kaltenecker, P.; Jakabfi-Csepregi, R.; Kovács, K.; et al. Telomere Length and Telomerase Activity of Granulosa Cells and Follicular Fluid in Women Undergoing In Vitro Fertilization. Antioxidants 2023, 12, 419. https://doi.org/10.3390/antiox12020419
Péntek S, Várnagy Á, Farkas B, Mauchart P, Gödöny K, Varjas T, Kőszegi T, Kaltenecker P, Jakabfi-Csepregi R, Kovács K, et al. Telomere Length and Telomerase Activity of Granulosa Cells and Follicular Fluid in Women Undergoing In Vitro Fertilization. Antioxidants. 2023; 12(2):419. https://doi.org/10.3390/antiox12020419
Chicago/Turabian StylePéntek, Sándor, Ákos Várnagy, Bálint Farkas, Péter Mauchart, Krisztina Gödöny, Tímea Varjas, Tamás Kőszegi, Péter Kaltenecker, Rita Jakabfi-Csepregi, Kálmán Kovács, and et al. 2023. "Telomere Length and Telomerase Activity of Granulosa Cells and Follicular Fluid in Women Undergoing In Vitro Fertilization" Antioxidants 12, no. 2: 419. https://doi.org/10.3390/antiox12020419