Analysis of Membrane Type-1 Matrix Metalloproteinase (MT1-MMP, MMP14) in Eutopic and Ectopic Endometrium and in Serum and Endocervical Mucus of Endometriosis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients and Sample Collection
2.2. Immunohistochemical Analysis and Quantification
2.3. MT1-MMP ELISA
2.4. Statistics
3. Results
3.1. Identification of MT1-MMP Localization in the Human Uterus and Ovarian Endometriosis
3.2. Quantification of MT1-MMP in Serum and Endocervical Mucus Samples of Patients with and without Endometriosis
4. Discussion
4.1. Localization of MT1-MMP in the Uterus
4.2. Localization of MT1-MMP in Adenomyosis and Endometriosis
4.3. Serum Levels of MT1-MMP in Cases with Endometriosis
4.4. Endocervical Mucus Samples of MT1-MMP in Endometriosis
4.5. Correlation of Serum/Endocervical Mucus Levels of MT1-MMP with Clinical Parameters and Clinical Implications
4.6. Strengths and Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Tissues | EM/EN−/AM− | EM/EN−/AM+ | EM EN+/AM− | EM EN+/AM+ | OV |
---|---|---|---|---|---|
All samples | n = 3 | n = 12 | n = 5 | n = 8 | n = 6 |
Median age ± SD | 45 ± 4.4 | 41.5 ± 4.7 | 43 ± 2.8 | 46.5 ± 3.8 | 38 ± 8.4 |
Proliferative | n = 2 | n = 7 | n = 2 | n = 6 | |
Secretory | n = 1 | n = 2 | n = 2 | n = 1 | |
Unknown | n = 3 | n = 1 | n = 1 |
Serum Samples | Mucus Samples | |||
---|---|---|---|---|
EN− | EN+ | EN− | EN+ | |
(n) | 61 | 71 | 87 | 106 |
Median age ± SD | 27 ± 7.9 | 34 ± 7.1 | 28 ± 8.2 | 33 ± 7.1 |
BMI (kg/m2) | 21.8 ± 6.3 | 23.7 ± 5.2 | 21.8 ± 4.6 | 22.9 ± 4.4 |
Smoking n (%) | n = 12 (19.7) | n = 17 (23.9) | n = 23 (26.4) | n = 24 (22.6) |
Allergy n (%) | n = 31 (50.8) | n = 34 (47.9) | n = 44 (50.6) | n = 58 (54.7) |
Menstrual phase (n) | ||||
Proliferative | 19 | 15 | 34 | 37 |
Secretory | 28 | 16 | 47 | 48 |
Menstruation | 8 | 9 | - | - |
Unknown | 6 | 31 | 6 | 21 |
Contraception use (n) | ||||
Yes | 28 | 35 | 22 | 36 |
No | 33 | 36 | 65 | 70 |
Fertility | ||||
Yes | 12 | 26 | 24 | 39 |
No | 8 | 19 | 14 | 30 |
Unknown | 41 | 26 | 49 | 37 |
Pain (n) | ||||
Dysmenorrhea | ||||
Yes | 48 | 44 | 70 | 83 |
No | 13 | 25 | 17 | 22 |
Unknown | - | 2 | - | 1 |
Dyspareunia | ||||
Yes | 26 | 39 | 40 | 62 |
No | 32 | 30 | 41 | 44 |
Unknown | 3 | 2 | 6 | - |
Dyschezia | ||||
Yes | 18 | 26 | 27 | 44 |
No | 43 | 45 | 56 | 62 |
Unknown | - | - | 4 | - |
Dysuria | ||||
Yes | 11 | 15 | 19 | 29 |
No | 50 | 56 | 68 | 77 |
Unknown | - | - | - | - |
EM a | OV b | Adenomyosis c | |
---|---|---|---|
HSCORE | |||
Mean | 91 | 31 | 149 |
SEM | 15.9 | 10.2 | 15.5 |
p-values | 0.0325 a,b | 0.0003 b,c | 0.024 a,c |
N | 16 | 6 | 20 |
Age | 45 ± 6.6 | 38 ± 8.4 | 44.5 ± 5.0 |
Percentage of stained glands | |||
Mean | 65 | 32 | 92 |
SEM | 9.2 | 3.0 | 10.5 |
p-values | n.s. a,b | 0.0002 b,c | 0.037 a,c |
N | 16 | 6 | 20 |
Age | 45 ± 6.6 | 38 ± 8.4 | 44.5 ± 5.0 |
Without Endometriosis | With Endometriosis | |||||
---|---|---|---|---|---|---|
Phases | Menstrual a | Proliferative b | Secretory c | Menstrual d | Proliferative e | Secretory f |
Samples (n) | 8 | 18 | 29 | 9 | 15 | 16 |
Median age | 26.5 ± 10.4 | 27 ± 8.7 | 28 ± 7.6 | 31 ± 6.3 | 37 ± 6.3 | 32 ± 6.6 |
Mean (ng/mL) | 0.7 | 0.6 | 0.8 | 0.7 | 4.1 | 0.6 |
SEM | 0.3 | 0.2 | 0.3 | 0.3 | 3.7 | 0.4 |
Range (ng/mL) | 0.1–2.9 | 0–3.3 | 0–7.7 | 0–2.2 | 0–57.2 | 0–5.7 |
p-values | n.s. a,b | n.s. a,c n.s. b,c | n.s. a,d | ≤0.05 d,e 0.042 b,e | ≤0.05 e,f n.s. d,f n.s. c,f |
A | Without Endometriosis | With Endometriosis | ||
---|---|---|---|---|
Samples (n) | 61 | 71 | ||
Median age | 27 ± 7.9 | 34 ± 7.1 | ||
Mean (ng/mL) | 0.7 | 1.3 | ||
SEM | 0.2 | 0.8 | ||
Range (ng/mL) | 0–7.7 | 0–57.2 | ||
p-value | 0.0016 | |||
B | Contraception | |||
w/o EN, w/o c a | w/o EN, w c b | w EN, w/o c c | w EN, w c d | |
Samples (n) | 33 | 28 | 36 | 35 |
Median age | 28 ± 9.2 | 25 ± 4.9 | 34 ± 7.3 | 34 ± 6.9 |
Mean (ng/mL) | 0.8 | 0.5 | 0.7 | 2.0 |
SEM | 0.3 | 0.2 | 0.2 | 1.6 |
Range (ng/mL) | 0–7.7 | 0–3.3 | 0–5.7 | 0–57.2 |
p-values | n.s. a,b | n.s. b,c 0.043 a,c | n.s. c,d 0.030 b,d |
Without Endometriosis | With Endometriosis | |||
---|---|---|---|---|
Proliferative a | Secretory b | Proliferative c | Secretory d | |
Samples (n) | 32 | 49 | 34 | 51 |
Median age | 31 ± 9.1 | 27 ± 7.4 | 30.5 ± 6.4 | 34 ± 6.5 |
Mean (ng/mL) | 4.1 | 2.8 | 4.6 | 3.5 |
SEM | 0.3 | 0.2 | 0.4 | 0.3 |
Range (ng/mL) | 0–7.6 | 0–6.9 | 0–14 | 0–9.3 |
p-values | 0.0006 a,b | n.s. b,c n.s. a,c | 0.01 c,d n.s. b,d |
A | Without Endometriosis | With Endometriosis | ||
---|---|---|---|---|
Samples (n) | 87 | 106 | ||
Median age | 28 ± 8.2 | 33 ± 7.1 | ||
Mean (ng/mL) | 3.2 | 3.6 | ||
SEM | 0.2 | 0.2 | ||
Range (ng/mL) | 0–7.6 | 0–14 | ||
p-value | n.s. | |||
B | Contraception | |||
w/o EN, w/o c a | w/o EN, w c b | w EN, w/o c c | w EN, w c d | |
Samples (n) | 65 | 22 | 70 | 36 |
Median age | 30 ± 8.5 | 27 ± 7.2 | 32.5 ± 7.2 | 33 ± 6.8 |
Mean (ng/mL) | 3.4 | 2.7 | 3.8 | 3.2 |
Range (ng/mL) | 0–7.6 | 0–5.4 | 0–9.3 | 0–14 |
SEM | 0.2 | 0.4 | 0.2 | 0.4 |
p-values | n.s. a,b | n.s. a,c n.s. b,c | 0.003 c,d n.s. b,d |
A | Serum MT1-MMP Levels | |||||
---|---|---|---|---|---|---|
Mean (ng/mL) ± SEM | ||||||
W/o EN | W EN | p-Values | Without Pain | With Pain | p-Values | |
BMI (kg/m2) | 23.9 ± 0.8 | 24.4 ± 0.6 | n.s. | |||
Age | 28.9 ± 1.0 | 34.8 ± 0.8 | 0.0001 | |||
Dysmenorrhea | n = 130 | 0.97 ± 0.3 | 1.10 ± 0.7 | n.s. | ||
Dysuria | n = 131 | 1.18 ± 0.5 | 0.22 ± 0.1 | n.s. | ||
Dyschezia | n = 132 | 1.24 ± 0.6 | 0.52 ± 0.2 | n.s. | ||
Dyspareunia | n = 127 | 0.77 ± 0.2 | 1.46 ± 1.1 | n.s. | ||
B | Endocervical Mucus MT1-MMP Levels | |||||
Mean (ng/mL) ± SEM | ||||||
W/o EN | W EN | p-Values | Without Pain | With Pain | p-Values | |
BMI (kg/m2) | 22.9 ± 0.5 | 23.4 ± 0.4 | n.s. | |||
Age | 30.8 ± 0.9 | 33.9 ± 0.7 | n.s. | |||
Dysmenorrhea | n = 192 | 3.18 ± 0.3 | 3.49 ± 0.2 | n.s. | ||
Dysuria | n = 193 | 3.39 ± 0.2 | 3.52 ± 0.3 | n.s. | ||
Dyschezia | n = 189 | 3.46 ± 0.2 | 3.50 ± 0.2 | n.s. | ||
Dyspareunia | n = 187 | 3.56 ± 0.2 | 3.39 ± 0.2 | n.s. |
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Maoga, J.B.; Riaz, M.A.; Mwaura, A.N.; Mecha, E.; Omwandho, C.O.A.; Scheiner-Bobis, G.; Meinhold-Heerlein, I.; Konrad, L. Analysis of Membrane Type-1 Matrix Metalloproteinase (MT1-MMP, MMP14) in Eutopic and Ectopic Endometrium and in Serum and Endocervical Mucus of Endometriosis. Biomedicines 2023, 11, 2730. https://doi.org/10.3390/biomedicines11102730
Maoga JB, Riaz MA, Mwaura AN, Mecha E, Omwandho COA, Scheiner-Bobis G, Meinhold-Heerlein I, Konrad L. Analysis of Membrane Type-1 Matrix Metalloproteinase (MT1-MMP, MMP14) in Eutopic and Ectopic Endometrium and in Serum and Endocervical Mucus of Endometriosis. Biomedicines. 2023; 11(10):2730. https://doi.org/10.3390/biomedicines11102730
Chicago/Turabian StyleMaoga, Jane B., Muhammad A. Riaz, Agnes N. Mwaura, Ezekiel Mecha, Charles O. A. Omwandho, Georgios Scheiner-Bobis, Ivo Meinhold-Heerlein, and Lutz Konrad. 2023. "Analysis of Membrane Type-1 Matrix Metalloproteinase (MT1-MMP, MMP14) in Eutopic and Ectopic Endometrium and in Serum and Endocervical Mucus of Endometriosis" Biomedicines 11, no. 10: 2730. https://doi.org/10.3390/biomedicines11102730