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A novel third mesh-like myometrial layer connects the longitudinal and circular muscle fibers -A potential stratum to coordinate uterine contractions.

ABSTRACT: Periodic myometrial contraction is one of the important uterine functions to achieve embryo implantation and parturition. Although it is well-known that the mammalian myometrium is composed of longitudinal (outer) and circular (inner) layers, the precise mechanisms that coordinate both muscular contractions to produce peristaltic movements remain unclear. Recently, by treatment with our modified Clear Unobstructed Brain Imaging Cocktails and Computational analysis (CUBIC) tissue-clearing method, we obtained well-contrasted three-dimensional images of the transparent murine ovary using enhanced green fluorescent protein (EGFP) transgenic mice and light-sheet microscopy. Consequently, to investigate accurate anatomical connections between outer and inner myometrial fibers, we observed whole structures of the myometrium using a transparent murine uterus. By this method, we identified a novel muscle layer, a middle layer of the myometrium, which anatomically connects the conventional outer longitudinal and inner circular muscles. This new layer was visualized as a mesh-like structure and this structure was observed throughout the whole uterus from proximal to distal sites. In this area, CD31-positive vessels were abundantly localized around the mesh-like muscle fibers. In addition, CD34-positive uterine telocytes and tubulin ?-3-positive nerve fibers were closely located in this middle layer. These findings indicate the presence of a novel mesh-like stratum that connects longitudinal and circular muscle layers, and suggest its coordinating role in myometrial contractions.

SUBMITTER: Kagami K

PROVIDER: S-EPMC7237439 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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A novel third mesh-like myometrial layer connects the longitudinal and circular muscle fibers -A potential stratum to coordinate uterine contractions.

Kagami Kyosuke K Ono Masanori M Iizuka Takashi T Matsumoto Takeo T Hosono Takashi T Sekizuka-Kagami Naomi N Shinmyo Yohei Y Kawasaki Hiroshi H Fujiwara Hiroshi H

Scientific reports 20200519 1

Periodic myometrial contraction is one of the important uterine functions to achieve embryo implantation and parturition. Although it is well-known that the mammalian myometrium is composed of longitudinal (outer) and circular (inner) layers, the precise mechanisms that coordinate both muscular contractions to produce peristaltic movements remain unclear. Recently, by treatment with our modified Clear Unobstructed Brain Imaging Cocktails and Computational analysis (CUBIC) tissue-clearing method, ...[more]

PMID: 32427986

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Project description:The mechanisms used to coordinate uterine contractions are not known. We develop a new model based on the proposal that there is a maximum distance to which action potentials can propagate in the uterine wall. This establishes "regions", where one action potential burst can rapidly recruit all the tissue. Regions are recruited into an organ-level contraction via a stretch-initiated contraction mechanism (myometrial myogenic response). Each uterine contraction begins with a regional contraction, which slightly increases intrauterine pressure. Higher pressure raises tension throughout the uterine wall, which initiates contractions of more regions and further increases pressure. The positive feedback synchronizes regional contractions into an organ-level contraction. Cellular automaton (CA) simulations are performed with Mathematica. Each "cell" is a region that is assigned an action potential threshold. An anatomy sensitivity factor converts intrauterine pressure to regional tension through the Law of Laplace. A regional contraction occurs when regional tension exceeds regional threshold. Other input variables are: starting and minimum pressure, burst and refractory period durations, enhanced contractile activity during an electrical burst, and reduced activity during the refractory period. Complex patterns of pressure development are seen that mimic the contraction patterns observed in laboring women. Emergent behavior is observed, including global synchronization, multiple pace making regions, and system memory of prior conditions. The complex effects of nifedipine and oxytocin exposure are simulated. The force produced can vary as a nonlinear function of the number of regions. The simulation directly links tissue-level physiology to human labor. The concept of a uterine pacemaker is re-evaluated because pace making activity may occur well before expression of a contraction. We propose a new classification system for biological CAs that parallels the 4-class system of Wolfram. However, instead of classifying the rules, biological CAs should classify the set of input values for the rules that describe the relevant biology.

Project description:ObjectiveInfection triggers inflammation that, in turn, enhances the expression of contractile-associated factors in myometrium and increases the risk of preterm delivery. In this study, we assessed vitamin D regulation of inflammatory markers, contractile-associated factors, steroid hormone receptors, and NFκB pathway proteins in human uterine myometrial smooth muscle (UtSM) cells that were cultured in an inflammatory environment.Study designInflammatory environment was simulated for UtSM cells by coculturing them with monocyte lineage (THP1) cells. We measured the expression of inflammatory markers, contractile-associated factors, steroid hormone receptors, and NFκB pathway proteins in UtSM cells that were cultured with THP1 cells in the presence and absence of vitamin D by real time polymerase chain reaction and Western blot analysis.ResultsMonocytes secreted monocyte inflammatory protein-1α and -1β, interleukin (IL)-1β and 6, and tumor necrosis factor-α into the conditioned medium. In the UtSM cells that had been cocultured with THP1 cells, there was a significant (P < .05) increase in the expression of inflammatory markers IL-1β, -6, and -13 and tumor necrosis factor-α; the contractile-associated factors connexin-43, Cox-2, and prostaglandin F2α receptor; the estrogen receptor α, and progesterone receptors A and B. Vitamin D treatment of cocultures decreased (P < .05) the expression of inflammatory markers and contractile-associated factors in UtSM cells. Similarly, vitamin D decreased estrogen receptor α and progesterone receptors A-to-B ratio in UtSM cells that were cocultured with THP1 cells. In addition, vitamin D treatment significantly (P < .05) decreased monocyte-induced p-IκBα in cytosol and NFκB-p65 in the nucleus and increased IκBα in cytosol in UtSM cells.ConclusionOur results suggest that vitamin D treatment decreases inflammation-induced cytokines and contractile-associated factors in the uterine myometrial smooth muscle cells through the NFκB pathway.

Dataset Information

A novel third mesh-like myometrial layer connects the longitudinal and circular muscle fibers -A potential stratum to coordinate uterine contractions.

Publications

A novel third mesh-like myometrial layer connects the longitudinal and circular muscle fibers -A potential stratum to coordinate uterine contractions.

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