Pig Pregnancies after Transfer of Allogeneic Embryos Show a Dysregulated Endometrial/Placental Cytokine Balance: A Novel Clue for Embryo Death?
Abstract
:1. Introduction
2. Materials and Methods
2.1. Experimental Design
2.2. Animals
2.3. Estrus Detection and Artificial Insemination
2.4. Embryo Recovery and Embryo Transfer
2.5. Embryo and Corpora Lutea Evaluation
2.6. Tissue Collection and Preparation
2.7. Cytokine Analysis
2.8. Protein Measurement
2.9. Statistical Analysis
3. Results
3.1. Reproductive Performance at Day 18 or 24 of Pregnancy after AI or ET
3.2. Variations on the Levels of Cytokines During the Peri-Implantation Period of Pregnancy
3.2.1. Pro-Inflammatory Cytokines
3.2.2. Anti-Inflammatory Cytokines
3.3. The IL-10:TNF-α Ratio
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Group | Corpora Lutea (n, mean ± sem) | Transferred Morulae/ET (n) | Total Recovered Embryos n (%) * | Normal Recovered Embryos n (%) * | Delayed Recovered Embryos n (%) ** |
---|---|---|---|---|---|
C+ | 94 (23.5 ± 1.0) | - | 76 (80.9) a | 72 (76.6) a | 4 (5.3) c |
ET | 90 (22.5 ± 1.6) | 92 | 54 (58.7) b | 42 (45.6) b | 12 (22.2) d |
Day 18 | Day 24 | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
CK | C− | C+ | C+ PL | ET | ET PL | C− | C+ IPA | C+ PL | C+ NIPA | ET IPA | ET PL | ET NIPA |
GM-CSF | 40 ± 9.1 | 75.7 ± 19.2 | 52.3 ± 11.6 | 41.48 ± 13.5 | 42.1 ± 9.5 | 128.6 ± 74.5 | 47.2 ± 21.3 | 108.3 ± 13.1 | 113.0 ± 51 | 25.8 ± 6.2 | 84.1 ± 13.1 | 17.7± 5.7 |
IFN-γ | 20,899.9 ± 5552.5 | 33,831.3 ± 9468.4 | 22,930.4 ± 5044.1 | 13,246.1 ± 2992.2 | 12,487.8 ± 2810 | 11,582.9 ± 2623.8 | 14,606.5 ± 634.5 | 21,030 ± 3019.4 | 30,452.2 ± 14,028.2 | 16,247.2 ± 5057.7 | 27,062.1 ± 7529.8 | 7820.2 ± 1636.2 |
IL-12 | 37.5 ± 30.7 | 23.3 ± 6.5 | 23.7 ± 4.5 | 29.9 ± 2.5 | 19.7 ± 2.5 | 187.4 ± 99.5 | 41.3 ± 15.7 | 0.0 ± 0.0 | 150.1 ± 101.5 | 28.3 ± 7.6 | 0.0 ± 0.0 | 30.3 ± 5.6 |
IL-18 | 3961.9 ± 778.3 | 13,493.9 ± 5363.5 | 6785.1 ± 482.5 | 11,497.2 ± 1106.5 | 8027.5 ± 1299.7 | 8914.1 ± 2895.4 | 7225.7 ± 2657.5 | 10,320.4 ± 2786.1 | 9367.8 ± 1691.2 | 8990.7 ± 2252 | 13,509.3 ± 3322.1 | 3403.2 ± 738.3 |
IL-1α | 91.6 ± 20.2 | 113.2 ± 24.4 | 112.3 ± 26.5 | 147.2 ± 15.7 | 97 ± 31.2 | 98.05 ± 30.7 | 96.7 ± 17.9 | 37.4 ± 7.9 | 118.6 ± 38.8 | 168.6 ± 24.5 | 147.5 ± 38.5 | 88.7 ± 13.4 |
IL-1β | 103.6 ± 21.7 | 363.3 ± 129.1 | 6170.5 ± 2716.6 | 253.5 ± 38.2 | 7674.7 ± 1759.4 | 454.3 ± 138.1 | 98.2 ± 31.7 | 15.6 ± 15.6 | 242.3 ± 156.7 | 202.4 ± 37.8 | 49.3 ± 13.6 | 73.9 ± 18.6 |
IL-1RA | 719.5 ± 272.1 | 2042 ± 801.2 | 1749.2 ± 299.6 | 1575.6 ± 179.7 | 1682.7 ± 367.2 | 914.5 ± 95.3 | 2344.1 ± 647.4 | 5775.5 ± 1973.9 | 1714.2 ± 320.3 | 1279.8 ± 289.9 | 14,924.7 ± 3739.3 | 462.8 ± 135.5 |
IL-2 | 33.9 ± 13.5 | 153.2 ± 53.7 | 61.2 ± 16.6 | 30 ± 6.2 | 24.1 ± 1.6 | 519.7 ± 174.3 | 70.9 ± 15.1 | 268.3 ± 59.3 | 250.4 ± 169.5 | 30.2 ± 9.8 | 300.2 ± 83.1 | 29.1 ± 8.3 |
IL-4 | 49.7 ± 16.2 | 34.3 ± 13.9 | 20.9 ± 4.6 | 14 ± 3.8 | 20.4 ± 7.2 | 81.1 ± 49.3 | 103.1 ± 13.9 | 28.7 ± 1.7 | 333.2 ± 228.2 | 41.3 ± 18.3 | 19.5 ± 5.1 | 33.8 ± 12.2 |
IL-6 | 0.0 ± 0.0 | 0.0 ± 0.0 | 0.0 ± 0.0 | 0.0 ± 0.0 | 0.0 ± 0.0 | 0.0 ± 0.0 | 56.4 ± 13.3 | 40.9 ± 18.4 | 35.7 ± 20 | 85.8 ± 25.4 | 136.2 ± 34.2 | 11.7 ± 5.4 |
IL-8 | 0.8 ± 0.1 | 0.5 ± 0.1 | 0.7 ± 0.1 | 0.5 ± 0.04 | 0.6 ± 0.0 | 0.8 ± 0.8 | 1.1 ± 0.1 | 0.6 ± 0.1 | 0.7 ± 0.2 | 0.9 ± 0.06 | 0.6 ± 0.1 | 1.1 ± 0.1 |
TGF- β 1 | 888.3 ± 162.6 | 2300.4 ± 563.9 | 1739.5 ± 192.5 | 2092.4 ± 300.1 | 1995.1 ± 153.5 | 2062.3 ± 417.9 | 1358.2 ± 211.1 | 2936.9± | 2848.5 ± 987.7 | 1387.5 ± 230.3 | 1856.1 ± 327.8 | 1208.1 ± 82.3 |
TGF- β 2 | 764 ± 195.6 | 1584.9 ± 147.6 | 2887.6 ± 688.1 | 1650.5 ± 294.1 | 3652.3 ± 552.1 | 1158.7 ± 228.5 | 1012.8 ± 237.3 | 1549.9 ± 397.4 | 1642.4 ± 631.9 | 842.8 ± 150.7 | 1343.9 ± 145.7 | 1217 ± 274.4 |
TGF- β 3 | 14.5 ± 5.1 | 21.4 ± 3.1 | 15.7 ± 3.3 | 22.8 ± 2.6 | 25.3 ± 7.4 | 16.9 ± 3.8 | 16.3 ± 2.5 | 15.9 ± 4.5 | 31.9 ± 10.8 | 18.1 ± 3.5 | 17.6 ± 3.4 | 22.6 ± 3.8 |
IL-10 | 110.9 ± 30.7 | 31.5 ± 10.1 | 62.0 ± 14.3 | 30.4 ± 5.4 | 76.3 ± 11.7 | 769.2 ± 359.6 | 230.6 ± 50.5 | 146.2 ± 17.3 | 608.6 ± 396.4 | 71.7 ± 16.1 | 41.2 ± 18.7 | 63.5 ± 24 |
TNF-α | 375 ± 113.3 | 557.9 ± 178.4 | 444.1 ± 82.5 | 713.9 ± 402.2 | 244 ± 41.1 | 168.7 ± 27.2 | 189.8 ± 32.2 | 459.8 ± 85.7 | 305.3 ± 123.8 | 105.4 ± 26.6 | 548.9 ± 124.7 | 63.8 ± 13.3 |
IL-10:TNF-α (ratio) | 0.4 ± 0.1 | 0.07 ± 0.02 | 0.15 ± 0.04 | 0.08 ± 0.02 | 0.36 ± 0.1 | 4.8 ± 2.6 | 1.21 ± 0.2 | 0.36 ± 0.09 | 1.58 ± 0.4 | 0.89 ± 0.2 | 0.2 ± 0.05 | 1.59 ± 0.2 |
Treatment-Day 18 | Treatment-Day 24 | Endometrial Area-Day 24 | Day of Pregnancy | |||||||
---|---|---|---|---|---|---|---|---|---|---|
CK | C+ vs. C− EN | C+ vs. ET EN | C+ vs. ET PL | C+ vs. C− EN | C+ vs. ET EN | C+ vs. ET PL | IPA vs. NIPA C+ | IPA vs. NIPA ET | D18 vs. D24 C+ | D18 vs. D24 ET |
GM-CSF | 0.149 | 0.248 | 0.564 | 0.248 | 0.234 | 0.126 | 0.248 | 0.561 | 0.149 | 0.308 |
IFN-γ | 0.248 | 0.043 | 0.149 | 0.021 | 0.174 | 0.865 | 0.773 | 0.105 | 0.021 | 1 |
IL-12 | 0.386 | 0.564 | 0.386 | 0.149 | 0.496 | 1 | 0.248 | 0.908 | 0.386 | 0.865 |
IL-18 | 0.021 | 0.773.5 | 0.248 | 0.773 | 0.61 | 0.496 | 0.386 | 0.081 | 0.386 | 0.496 |
IL-1α | 0.564 | 0.248 | 0.564 | 1 | 0.062 | 0.007 | 0.773 | 0.01 | 0.773 | 0.734 |
IL-1β | 0.043 | 0.564.1 | 0.564 | 0.083 | 0.126 | 0.078 | 0.564 | 0.024 | 0.083 | 0.396 |
IL-1RA | 0.083 | 0.773 | 0.564 | 0.149 | 0.174 | 0.042 | 0.386 | 0.015 | 0.773 | 0.308 |
IL-2 | 0.043 | 0.021 | 0.043 | 0.021 | 0.06 | 0.734 | 0.386 | 0.814 | 0.149 | 0.864 |
IL-4 | 0.386 | 0.248 | 0.773 | 0.248 | 0.04 | 0.307 | 0.564 | 0.765 | 0.043 | 0.494 |
IL-6 | 1 | 1 | 1 | 0.014 | 0.61 | 0.173 | 0.248 | 0.045 | 0.014 | 0.03 |
IL-8 | 0.386 | 0.248 | 0.248 | 0.248 | 0.126 | 0.497 | 0.083 | 0.045 | 0.083 | 0.007 |
TGF- β 1 | 0.021 | 0.773 | 0.564 | 0.083 | 0.497 | 0.174 | 0.083 | 0.2 | 0.083 | 0.126 |
TGF- β 2 | 0.021 | 0.564 | 0.248 | 0.564 | 0.61 | 0.497 | 0.564 | 0.183 | 0.149 | 0.042 |
TGF- β 3 | 0.248 | 0.773 | 0.248 | 1 | 0.497 | 0.734 | 0.149 | 0.563 | 0.149 | 0.234 |
IL-10 | 0.043 | 0.773 | 0.564 | 0.386 | 0.026 | 0.016 | 0.773 | 0.952 | 0.021 | 0.494 |
TNF-α | 0.564 | 0.773 | 0.021 | 0.773 | 0.062 | 0.734 | 0.773 | 0.024 | 0.021 | 0.007 |
IL-10:TNF-α (ratio) | 0.234 | 0.631 | 0.3 | 0.112 | 0.1 | 0.564 | 0.126 | 0.105 | 0.002 | 0.009 |
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Martinez, C.A.; Rubér, M.; Rodriguez-Martinez, H.; Alvarez-Rodriguez, M. Pig Pregnancies after Transfer of Allogeneic Embryos Show a Dysregulated Endometrial/Placental Cytokine Balance: A Novel Clue for Embryo Death? Biomolecules 2020, 10, 554. https://doi.org/10.3390/biom10040554
Martinez CA, Rubér M, Rodriguez-Martinez H, Alvarez-Rodriguez M. Pig Pregnancies after Transfer of Allogeneic Embryos Show a Dysregulated Endometrial/Placental Cytokine Balance: A Novel Clue for Embryo Death? Biomolecules. 2020; 10(4):554. https://doi.org/10.3390/biom10040554
Chicago/Turabian StyleMartinez, Cristina A., Marie Rubér, Heriberto Rodriguez-Martinez, and Manuel Alvarez-Rodriguez. 2020. "Pig Pregnancies after Transfer of Allogeneic Embryos Show a Dysregulated Endometrial/Placental Cytokine Balance: A Novel Clue for Embryo Death?" Biomolecules 10, no. 4: 554. https://doi.org/10.3390/biom10040554
APA StyleMartinez, C. A., Rubér, M., Rodriguez-Martinez, H., & Alvarez-Rodriguez, M. (2020). Pig Pregnancies after Transfer of Allogeneic Embryos Show a Dysregulated Endometrial/Placental Cytokine Balance: A Novel Clue for Embryo Death? Biomolecules, 10(4), 554. https://doi.org/10.3390/biom10040554