Uterine peristalsis-induced stresses within the uterine wall may sprout adenomyosis

Shaked, Sivan; Jaffa, Ariel J.; Grisaru, Dan; Elad, David

doi:10.1007/s10237-014-0614-4

Cited by 41 publications

(27 citation statements)

References 28 publications

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“…Apart from its important role as an estrogen moderator, Sprr2a has wound healing and inflammation regulatory functions48 We found that Tff1 and Sprr2a1 were downregulated in the adenomyosis mouse model, implying that an increased estrogen level is associated with adenomyosis, and that an impaired wound healing ability of the endometrium may be involved in the development of adenomyosis. These findings are consistent with a recent study that identified a “tissue injury and repair” mechanism in the development of adenomyosis, in which uterine peristalsis led to the invasion of endometrial tissue into the myometrium, resulting in adenomyosis49 In the present study, Tff1 and Sprr2a1 were upregulated following GnRH agonist treatment, suggesting that GnRH agonists may decrease the production of estrogen and improve the repair capacity of the endometrium. Few studies have been carried out into the role of Aldh3b2 , and these are limited to neuroblastomas50 and keratinocytes,51 not adenomyosis.…”

Section: Discussionsupporting

confidence: 93%

Transcriptome analysis of endometrial tissues following GnRH agonist treatment in a mouse adenomyosis model

Guo

et al. 2017

DDDT

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PurposeAdenomyosis is a common, benign gynecological condition of the female reproductive tract characterized by heavy menstrual bleeding and dysmenorrhea. Gonadotropin-releasing hormone (GnRH) agonists are one of the medications used in adenomyosis treatment; however, their underlying mechanisms are poorly understood. Moreover, it is difficult to obtain endometrial samples from women undergoing such treatment. To overcome this, we generated an adenomyosis mouse model, which we treated with an GnRH agonist to determine its effect on pregnancy outcomes. We also analyzed endometrial gene expression following GnRH agonist treatment to determine the mechanisms that may affect pregnancy outcome in individuals with adenomyosis.MethodsNeonatal female mice were divided into a control group, an untreated adenomyosis group, and an adenomyosis group treated with a GnRH agonist (n=6 each). The pregnancy outcome was observed and compared among the groups. Then, three randomly chosen transcriptomes from endometrial tissues from day 4 of pregnancy were analyzed between the adenomyosis group and the GnRH agonist treatment group by RNA sequencing and quantitative reverse transcription polymerase chain reaction (PCR).ResultsThe litter size was significantly smaller in the adenomyosis group than in the control group (7±0.28 vs 11±0.26; P<0.05). However, the average live litter size was increased (10±0.28 vs 7±0.28; P<0.05) after GnRH agonist treatment. Three hundred and fifty-nine genes were differentially expressed in the GnRH agonist-treated group compared with the untreated group (218 were downregulated and 141 were upregulated). Differentially expressed genes were related to diverse biological processes, including estrogen metabolism, cell cycle, and metabolite biosynthesis.ConclusionGnRH agonist treatment appears to improve the pregnancy outcome of adenomyosis in a mouse model. Besides pituitary down-regulation, other possible mechanisms such as the regulation of cell proliferation may play a role in this. These new insights into GnRH agonist mechanisms will be useful for future adenomyosis treatment.

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Section: Discussionsupporting

confidence: 93%

Transcriptome analysis of endometrial tissues following GnRH agonist treatment in a mouse adenomyosis model

Guo

et al. 2017

DDDT

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“…[ 5 ] The frequency, amplitude, duration, and direction of muscle contractions were observed to change during the menstrual cycle in hormone-dependent ways. [ 6 ] Bulletti et al . [ 7 ] compared the UC patterns of women with or without endometriosis (EM) and found that patients with EM had UCs with higher frequency and greater basal muscle tone.…”

Section: Discussionmentioning

confidence: 99%

Expression of Potassium Channels in Uterine Smooth Muscle Cells from Patients with Adenomyosis

Shi

Jin

Leng

et al. 2016

Chinese Medical Journal

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Background:Adenomyosis (AM) has impaired contraction. This study aimed to explore the expression of potassium channels related to contraction in myometrial smooth muscle cells (MSMCs) of AM.Methods:Uterine tissue samples from 22 patients (cases) with histologically confirmed AM and 12 (controls) with cervical intraepithelial neoplasia were collected for both immunohistochemistry and real-time polymerase chain reaction to detect the expression of large conductance calcium- and voltage-sensitive K+ channel (BKCa)-α/β subunits, voltage-gated potassium channel (Kv) 4.2, and Kv4.3. Student's t-test was used to compare the expression.Results:The BKCa-α/β subunits, Kv4.2, and Kv4.3 were located in smooth muscle cells, glandular epithelium, and stromal cells. However, BKCa-β subunit expression in endometrial glands of the controls was weak, and Kv4.3 was almost undetectable in the controls. The expression of BKCa-α messenger RNA (mRNA) (0.62 ± 0.19-fold decrease, P < 0.05) and Kv4.3 mRNA (0.67 ± 0.20-fold decrease, P < 0.05) decreased significantly in the MSMCs of the control group compared with the AM group. However, there were no significant differences in BKCa-β subunit mRNA or Kv4.2 mRNA.Conclusions:The BKCa-α mRNA and the Kv4.3 mRNA are expressed significantly higher in AM than those in the control group, that might cause the abnormal uterus smooth muscle contractility, change the microcirculation of uterus to accumulate the inflammatory factors, impair the endometrium further, and aggravate the pain.

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“…However, increased production of estrogen leads to chronic hyperperistalsis with further damage at the JZ and progression of the pathology. Recently, computational modeling of physical stresses with the uterine wall in response to uterine hyperperistalsis revealed relatively large stresses with high gradients in space and time in the vicinity of the JZ . This simulation provided support to the basic cause for the TIAR hypothesis.…”

Section: Uterine Disease Development and Infertilitymentioning

confidence: 62%

Biomechanics of the human uterus

Myers

Elad

2017

WIREs Mechanisms of Disease

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The appropriate biomechanical function of the uterus is required for the execution of human reproduction. These functions range from aiding the transport of the embryo to the implantation site, to remodeling its tissue walls to host the placenta, to protecting the fetus during gestation, to contracting forcefully for a safe parturition and postpartum, to remodeling back to its nonpregnant condition to renew the cycle of menstruation. To serve these remarkably diverse functions, the uterus is optimally geared with evolving and contractile muscle and tissue layers that are cued by chemical, hormonal, electrical, and mechanical signals. The relationship between these highly active biological signaling mechanisms and uterine biomechanical function is not completely understood for normal reproductive processes and pathological conditions such as adenomyosis, endometriosis, infertility and preterm labor. Animal studies have illuminated the rich structural function of the uterus, particularly in pregnancy. In humans, medical imaging techniques in ultrasound and magnetic resonance have been combined with computational engineering techniques to characterize the uterus in vivo, and advanced experimental techniques have explored uterine function using ex vivo tissue samples. The collective evidence presented in this review gives an overall perspective on uterine biomechanics related to both its nonpregnant and pregnant function, highlighting open research topics in the field. Additionally, uterine disease and infertility are discussed in the context of tissue injury and repair processes and the role of computational modeling in uncovering etiologies of disease. WIREs Syst Biol Med 2017, 9:e1388. doi: 10.1002/wsbm.1388 For further resources related to this article, please visit the WIREs website.

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Uterine peristalsis-induced stresses within the uterine wall may sprout adenomyosis

Cited by 41 publications

References 28 publications

Transcriptome analysis of endometrial tissues following GnRH agonist treatment in a mouse adenomyosis model

Transcriptome analysis of endometrial tissues following GnRH agonist treatment in a mouse adenomyosis model

Expression of Potassium Channels in Uterine Smooth Muscle Cells from Patients with Adenomyosis

Biomechanics of the human uterus

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