ROLE OF MOESIN IN DEVELOPMENT OF ADENOMYOSIS AND POSSIBLE ASSOCIATION WITH OXIDATIVE STRESS
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Turkish Journal of Physiotherapy and Rehabilitation; 32(3)
ISSN 2651-4451 | e-ISSN 2651-446X
ROLE OF MOESIN IN DEVELOPMENT OF ADENOMYOSIS AND POSSIBLE
ASSOCIATION WITH OXIDATIVE STRESS
Tuqa Hazim Alajresh 1, Abdulsamie H. Alta'ee 1, Nadia Mudhar Al-Hilli 1
1
College of Medicine, University of Babylon, Hilla , Iraq
ABSTRACT
Adenomyosis is a commonly encountered benign uterine disease, affecting 19.5% of women of reproductive
age. Histopathologically it is characterized by the presence of ectopic endometrial tissue (endometrial glands
and/or stroma) in the myometrium, surrounded by hyperplastic and hypertrophic smooth muscle. This study
aims to determine if moesin (MSN) is a useful biomarker for detecting of women with adenomyosis and if
there possible association with oxidative stress. The study included 90 women divided into two groups (45)
healthy and (45) patients, and experimental research work was conducted during the period (from first of
October 2020 to the end of January 2021) ELISA technique was used to measures human MSN and total
antioxidant capacity (TAOC) in the blood. The current study found a highly significant difference between
patients and control groups in concentration of MSN where (p = 0.002) the level being higher in patients group.
and there was no significant difference between patients and control groups in concentration of total antioxidant
capacity where (p = 0.644). The conclusion of this study MSN may be use as biomarker aid in the diagnosis of
Adenomyosis and There is no oxidative stress associated with adenomyosis.
Keyword: Adenomyosis, moesin, total antioxidant capacity, oxidative stress, Iraq.
I. INTRODUCTION
Adenomyosis is defined as the presence of ectopic endometrial glands and stroma surrounded by hyperplastic
smooth muscle within the myometrium. It is a uterine disorder clinically presented with pelvic pain, abnormal
uterine bleeding (AUB) and infertility. Dysmenorrhoea and heavy menstrual bleeding is the most common
symptom) ; however, the clinical presentation of adenomyosis is often mixed and occasionally it may even be
asymptomatic (1).
Before the advancement of imaging techniques such as transvaginal ultrasound scan (TVUS) and magnetic
resonance imaging (MRI), adenomyosis could only be diagnosed by histology after hysterectomy. Two different
pathological aspects of adenomyosis are described: diffuse and focal forms (when a defined nodule is found, the
term adenomyoma is also used). Nevertheless, they are considered as two distinct entities because many differences
have been observed in pathogenesis, risk factors and clinical presentation (2).
Despite all these differences, the two conditions have many similarities in definition, symptomology and molecular
aberrations (3). A large number of women are affected by adenomyosis, which can adversely affect quality of life
(4).
Moesin, a protein encoded in human by the MSN gene, has been proposed as a biomarker for adenomyosis, and a
higher expression of moesin was noted in adenomyosis versus normal endometrium. An association between
moesin as a marker for EMT has been already proposed and may contribute to our understanding of the
pathophysiology of adenomyosis. Adenomyosis development mimics the process of tumor metastasis, which is
characterized by progressive transmyometrial invasion of endometrial cells and neovascularization in ectopic
lesions (5).
Moesin is a well conserved gene in many species and is present in many tissues, exerting various molecular actions,
such as regulation of the actin cytoskeleton and control of cell shape, cell adhesion or motility. Phosphorylation is
required for activation of moesin, and different activation signals regulate the functions of moesin by modulating
these intramolecular interactions. Phosphorylation of moesin acts as a switch to trigger cell motility (6).
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ISSN 2651-4451 | e-ISSN 2651-446X
Oxidative stress (OS) is defined as an imbalance situation for pro-oxidants and antioxidants (7). OS leads to
endothelial cell dysfunction. In the uterus, endothelial cell dysfunction results in many diseases, such as
preeclampsia and endometriosis and Adenomyosis. The aberrant expression of GPX in the eutopic endometrium
throughout the cycle suggests a pathological role in endometriosis and adenomyosis (8,9).
II. MATERIALS AND METHODS
This study was performed at the laboratory of Chemistry and Biochemistry Department, College of Medicine
University of Babylon. The subjects in this prospective case-control study, included a total of 90 subjects, 45 these
subjects suffering from Adenomyosis (45 female) and 45 apparently healthy control subjects. All samples were
collected during the period from the first of October 2020 to the end of January 2021 Samples were collected from
Maternity and Children Teaching Hospital in Hilla city , Babylon Province, Iraq.
Inclusion Criteria
All reproductive age women, newly diagnosed with adenomyosis before starting treatment, or during the course of
treatment.
Exclusion Criteria
1. Patients with endometeriosis.
2. patients with uterine fibroids.
3. patients with other uterus diseases
Body Mass Index (BMI)
Body mass index (BMI) is a ratio of a person weight to a height; it commonly used to classify weight as healthy or
unhealthy . BMI calculated by below equation as follow (10):
Serum Moesin levels were measured using commercially available enzyme-linked immunosorbent assay (ELISA)
kits according to manufacturers' instructions (Bioassay Technology Laboratory, respectively Moesin levels ranged
from 0.1to 40 ng/ml).
Total antioxidant capacity using ELISA technology is used to determination was supplied with the kit provided by
Bioassay-china.
Results and Discussion
Demographic characteristics of the subject of study
This study involved 45 patients with adenomyosis and 45 healthy subjects (control group) in different areas of
Babylon Province in Iraq.
The comparison of mean age between patients and control group and the frequency distribution of
patients and control subjects according to age
The comparison of mean age between patients and control group and the frequency distribution of patients and
control subjects according to age is shown in Table 3-1. The mean age of patients’ group was 44.80 ± 5.76 years
and that of control group was 42.53 ± 7.39 years and there was no significant difference in mean age between
patients and control groups (p = 0.108). The frequency distribution of patients and control subjects is also shown
in Table 1. Regarding patients group, there were 10 (22.2 %) between 35 and 39 years of age, 26 (57.8 %) between
40 and 49 years of age and 9 (20.0 %) between 50 and 60 years.
Adenomyosis is a common disease, but its etiology is not fully understood (11,12). Dysmenorrhea, menorrhagia,
and chronic pelvic pain are common symptoms (13,14).
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ISSN 2651-4451 | e-ISSN 2651-446X
It affects women of all age groups. Approximately 20% of cases of Adenomyosis involve women younger than 40
and 80% are aged 40 to 50 (15,16).
Table 1: The comparison of mean age between patients and control group and the frequency distribution of patients and
control subjects according to age
Characteristic Control Patients P
n= 45 n = 45
Age (years)
Mean ±SD 42.53 ±7.39 44.80 ±5.76 0.108 I
Range 35 -60 35 -57 NS
35-39, n (%) 22 (48.9 %) 10 (22.2 %)
40-49, n (%) 15 (33.3 %) 26 (57.8 %)
50-60, n (%) 8 (17.8 %) 9 (20.0 %)
n: number of cases; SD: standard deviation; I: independent samples t- test; NS: not significant at p > 0.05
The comparison of mean body mass index (BMI) between patients and control group and the frequency
distribution of patients and control subjects according to BMI
The comparison of mean BMI between patients and control group and the frequency distribution of patients and
control subjects according to age is shown in Table 2. The mean BMI of patients’ group was 31.20 ±2.76 kg/m2
and that of control group was 29.91 ±4.38 kg/m2 and there was no significant difference in mean BMI between
patients and control groups (p = 0.097). The frequency distribution of patients and control subjects according to
BMI is also shown in Table 2. Regarding patients group, there were 1 (2.2 %) as normal eight, 14 (31.1 %) as
overweight, 27 (60.0 %) as class I obesity, 3 (6.7 %) as class II obesity and no one as class III obesity.
Adenomyosis and obesity connection are mentioned. Trabert et al.(17) compared normal and overweight women
in their study and found that the risk of adenomyosis in overweight/obese patients increased compared to normal
weight patients and there was a strong link between obesity and adenomyosis. Similarly, Koike et al.(18) and
Templeman et al.(19) emphasized that obesity plays a role in the etiology of adenomyosis. Ferenczy (20) and
Benson and Sneeden (21) suggested that obesity is not associated with adenomyosis.
Table 2: The comparison of mean body mass index (BMI) between patients and control group and the frequency distribution
of patients and control subjects according to BMI.
Characteristic Control Patients P
n= 45 n = 45
BMI (kg/m2)
Mean ±SD 29.91 ±4.38 31.20 ±2.76 0.097 I
Range 23.1 -41 24.7 -37.3 NS
Normal, n (%) 5 (11.1 %) 1 (2.2 %)
Overweight, n (%) 21 (46.7 %) 14 (31.1 %)
Class I obesity, n (%) 13 (28.9 %) 27 (60.0 %)
Class II obesity, n (%) 5 (11.1 %) 3 (6.7 %)
Class III obesity, n (%) 1 (2.2 %) 0 (0.0 %)
n: number of cases; SD: standard deviation; I: independent samples t-test; NS: not significant at p > 0.05
Past Obstetric History
Comparison of past obstetric history characteristics between patients and control group including parity, abortion
and previous cesarean section is shown in Table 3. The mean parity of patients was 4.42 ± 1.252 and that of control
group was 3.76 ± 1.54 and the difference was significant (p = 0.027); mean parity being more in patients. A high
percentage of women with Adenomyosis are multiparous(22). Pregnancy might facilitate the formation of
adenomyosis by allowing adenomyotic foci to be included in the myometrium due to the invasive nature of the
trophoblast on the extension of the myometrial fibers (23).
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In addition, Adenomyotic tissue may have a higher ratio of estrogen receptors and the hormonal milieu of pregnancy
may favor the development of islands of ectopic Endometrium (24). Alternatively, there may be an increased
acceptance of hysterectomy in multiparous women. Many studies (25) reported that adenomyosis is common in
multiparous women in parallel with the results of our study. In the study conducted by Lee et al. (26) it was stated
that 90% of the patients with adenomyosis were multiparous. Bergholt et al.(27) suggested that there was no
significant difference between the number of parity and adenomyosis in their study, and this result is not compatible
with the results of our study.
With respect to rate of abortion, the median was 2 in both groups and there was no significant difference (p =
0.117). Regarding number of previous cesarean sections, the median was higher in patients group in comparison
with control group, 2 versus 0, respectively and the difference was highly significant (p = 0.009). Evidence
regarding a significantly increased risk of prior uterine surgery in women with adenomyosis is inconsistent. Clinical
data have supported the hypothesis that adenomyosis results when endometrial glands invade the myometrial layer,
with surgical disruptions of the endometrial-myometrial border increasing the risk of adenomyosis in some studies
(28).
Levgur et al. and Parazzini et al. reported that patients who had undergone pregnancy termination via dilation and
curettage demonstrated higher rates of adenomyosis than women without pregnancy terminations (29) and this
studies not compatible with our study. Whitted et al. observed an increased prevalence of adenomyosis in subjects
who had prior cesarean section(30). Another group of patients with increased risk of adenomyosis is patients with
previous cesarean section (31) and this compatible with our study.
Table 3: Comparison of past obstetric history characteristics between patients and control group including parity, abortion
and previous cesarean section.
Characteristic Control Patients P
n= 45 n = 45
Parity
Mean ±SD 3.76 ± 1.54 4.42 ± 1.252 0.027 I
Range 1 -7 2 -7 S
Abortion
Median (IQR) 1 (2) 1 (2) 0.117 M
Range 0 -3 0 -3 NS
Cesarean section
Median (IQR) 0 (2) 2 (4) 0.009 M
Range 0 -4 0 -5 HS
n: number of cases; SD: standard deviation; I: independent samples t-test; M: Mann Whitney U test; S: significant at p ≤
0.05; NS: not significant at p > 0.05; HS: highly significant at p ≤ 0.01.
Comparison of mean serum total anti-oxidant capacity (TAOC) and mean serum MSN between patients
and control groups
The comparison of mean serum TAOC and mean serum MSN between patients and control groups is shown in
Table 4. Mean serum TAOC of patients group was 72.68 ±18.76 and that of control groups was 74.29 ±13.73 and
there was no significant difference between patients and control groups (p = 0.644). Mean serum MSN of patients
group was 48.37 ±7.65 and that of control group was 41.85 ±11.09 and there was highly significant difference
between patients and control groups (p = 0.002); the level being higher in patients group. Moesin, a protein encoded
in human by the MSN gene, has been proposed as a biomarker for adenomyosis. Using proteomic analysis, a higher
expression of moesin was noted in adenomyosis versus normal endometrium. Adenomyosis development mimics
the process of tumor metastasis, which is characterized by progressive trans myometrial invasion of endometrial
cells and neovascularization in ectopic lesions. To explain the invasiveness seen in adenomyosis, the authors
propose a further review of the phosphorylation of moesin in women with adenomyosis, as in certain tumors such
as invasive gastric adenocarcinoma, the extent of invasiveness correlates with moesin expression. ‘Moesin’ has
been proved as a unique biomarker of adenomyosis by Ohara R et al. in 2014, have proved they found that moesin
was overexpressed significantly in the stromal cells of adenomyotic foci compared to normal endometrium (32)
this compatible with our study.
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Table 4: Comparison of mean serum TAOC and mean serum MSN between patients and control groups.
Characteristic Control Patients P
n= 45 n = 45
TAOC
Mean ±SD 74.29 ±13.73 72.68 ±18.76 0.644 I
Range 37.26 -96.63 26.88 -108.65 NS
MSN
Mean ±SD 41.85 ±11.09 48.37 ±7.65 0.002 I
Range 4.38 -57.67 31.02 -63.12 HS
n: number of cases; SD: standard deviation; I: independent samples t-test; NS: not significant at p > 0.05; HS: highly
significant at p ≤ 0.01
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