International Journal of Molecular Sciences

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27 pages, 5670 KiB

Open AccessArticle

Environmental Enrichment Promotes Transgenerational Programming of Uterine Inflammatory and Stress Markers Comparable to Gestational Chronic Variable Stress

by Nayara A. Lopes, Mirela Ambeskovic, Stephanie E. King, Jamshid Faraji, Nasrin Soltanpour, Erin A. Falkenberg, Taylor Scheidl, Mansi Patel, Xin Fang, Gerlinde A. S. Metz and David M. Olson

Int. J. Mol. Sci. 2023, 24(4), 3734; https://doi.org/10.3390/ijms24043734 - 13 Feb 2023

Cited by 4 | Viewed by 2424

Abstract

Prenatal maternal stress is linked to adverse pregnancy and infant outcomes, including shortened gestation lengths, low birth weights, cardio-metabolic dysfunction, and cognitive and behavioural problems. Stress disrupts the homeostatic milieu of pregnancy by altering inflammatory and neuroendocrine mediators. These stress-induced phenotypic changes can [...] Read more.

Prenatal maternal stress is linked to adverse pregnancy and infant outcomes, including shortened gestation lengths, low birth weights, cardio-metabolic dysfunction, and cognitive and behavioural problems. Stress disrupts the homeostatic milieu of pregnancy by altering inflammatory and neuroendocrine mediators. These stress-induced phenotypic changes can be passed on to the offspring epigenetically. We investigated the effects of gestational chronic variable stress (CVS) in rats using restraint and social isolation stress in the parental F0 generation and its transgenerational transmission across three generations of female offspring (F1–F3). A subset of F1 rats was housed in an enriched environment (EE) to mitigate the adverse effects of CVS. We found that CVS is transmitted across generations and induces inflammatory changes in the uterus. CVS did not alter any gestational lengths or birth weights. However, inflammatory and endocrine markers changed in the uterine tissues of stressed mothers and their offspring, suggesting that stress is transgenerationally transmitted. The F2 offspring reared in EE had increased birth weights, but their uterine gene expression patterns remained comparable to those of stressed animals. Thus, ancestral CVS induced changes transgenerationally in fetal programming of uterine stress markers over three generations of offspring, and EE housing did not mitigate these effects. Full article

(This article belongs to the Special Issue Molecular Research in Uterine Biology and Pathophysiology)

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19 pages, 3996 KiB

Open AccessArticle

Detection of Circulating Tumor Cell-Related Markers in Gynecologic Cancer Using Microfluidic Devices: A Pilot Study

by Kim-Seng Law, Chung-Er Huang and Sheng-Wen Chen

Int. J. Mol. Sci. 2023, 24(3), 2300; https://doi.org/10.3390/ijms24032300 - 24 Jan 2023

Cited by 8 | Viewed by 3511

Abstract

The detection of circulating tumor cells (CTCs) is an emerging strategy for the early detection, prognostication, and identification of recurrent cancer. The clinical utility of CTC detection has been established, but few studies have employed this strategy for the detection of gynecologic cancers. [...] Read more.

The detection of circulating tumor cells (CTCs) is an emerging strategy for the early detection, prognostication, and identification of recurrent cancer. The clinical utility of CTC detection has been established, but few studies have employed this strategy for the detection of gynecologic cancers. Here, we present a novel, biochip-based microfluidic device for the detection of CTCs in gynecologic cancers. The study cohort included three patients with cervical cancer, eight with endometrial cancer, two with ovarian cancer, two with breast cancer, and one with vaginal small cell carcinoma. Four cancer type-specific molecular markers (PanCK, GATA3, HER2, and HE4), as well as CD13, were used for prognostication and recurrence detection, along with downstream genomic analysis. GATA3 and HER2 were markedly expressed in the patients with cervical cancer, and this expression was strongly correlated with the early detection of recurrent disease. All four molecular markers were expressed preoperatively in the patients with endometrial cancer, and the re-expression of different markers was observed at follow-up before recurrence was confirmed. CD13 was identified as an alternative prognostic marker for both cervical and endometrial cancer. Our pilot study indicated that the novel CTC detection system can be used for prognostication and early detection of disease recurrence, which needed further investigation. Full article

(This article belongs to the Special Issue Molecular Research in Uterine Biology and Pathophysiology)

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18 pages, 5233 KiB

Open AccessArticle

The N6-Methyladenosine Regulator ALKBH5 Mediated Stromal Cell–Macrophage Interaction via VEGF Signaling to Promote Recurrent Spontaneous Abortion: A Bioinformatic and In Vitro Study

by Yongbo Zhao, Jiani Sun and Liping Jin

Int. J. Mol. Sci. 2022, 23(24), 15819; https://doi.org/10.3390/ijms232415819 - 13 Dec 2022

Cited by 10 | Viewed by 2238

Abstract

Successful conception requires the synchrony of multiple systems and organs. Dysregulation of stromal cell–immune cell interactions has been proposed to be associated with recurrent spontaneous abortion. However, the mechanism of this regulation has not been well elucidated. N6-methyladenosine is one of the most [...] Read more.

Successful conception requires the synchrony of multiple systems and organs. Dysregulation of stromal cell–immune cell interactions has been proposed to be associated with recurrent spontaneous abortion. However, the mechanism of this regulation has not been well elucidated. N6-methyladenosine is one of the most common RNA modifications, and is involved in many pathological processes. Our group has demonstrated that abnormal patterns of m6A modification inhibit trophoblast invasion and contribute to adverse pregnancy outcomes. The association between m6A regulators and stromal cell–immune cell interactions is unclear. We obtained RNA-seq profiles from a GEO dataset and identified differentially expressed m6A regulators between healthy controls and patients with a recurrent spontaneous abortion history. ROC curves, functional enrichment and subclassification analysis were applied to elucidate the role of m6A regulators in pregnancy. We verified the expression of m6A regulators and constructed an overexpression cell line in a coculture system to reveal ALKBH5 function in stromal cell–macrophage interactions. We identified 11 differentially expressed m6A regulators between healthy controls and patients with a recurrent spontaneous abortion history. Then, we identified the correlation between “eraser” genes and “writer” genes. We tested the predictive abilities of the 11 m6A regulators based on another dataset and verified their expression in primary human endometrial stromal cells. We then subclassified three distinct patterns using the 11 genes and visualized genes related to immune infiltration and macrophage function in each cluster. ALKBH5 was proven to be correlated with recurrent spontaneous abortion. To verify the role of ALKBH5 in RSA, we constructed an ALKBH5-overexpression cell line. Finally, we cocultured the overexpression cell line with THP-1 cells. A decrease in M2 differentiation was observed, and this bias could be attributed to the hyposecretion of VEGF in stromal cells. N6-methyladenosine regulators play a pivotal role in stromal cell–immune cell interactions at the maternal–fetal interface. Overexpression of the m6A “eraser” gene ALKBH5 in stromal cells resulted in the hyposecretion of VEGF. Dysregulation of VEGF might impair macrophage recruitment and M2 differentiation, which could be the potential cause of recurrent spontaneous abortion. Full article

(This article belongs to the Special Issue Molecular Research in Uterine Biology and Pathophysiology)

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13 pages, 1307 KiB

Open AccessArticle

An Assessment of Metallothionein–Cadmium Binding in Rat Uterus after Subchronic Exposure Using a Long–Term Observation Model

by Marzenna Nasiadek, Joanna Stragierowicz and Anna Kilanowicz

Int. J. Mol. Sci. 2022, 23(23), 15154; https://doi.org/10.3390/ijms232315154 - 2 Dec 2022

Cited by 3 | Viewed by 1478

Abstract

Cadmium (Cd) is an environmental pollutant known to pose a public health issue. The mechanism of Cd toxicity on the uterus, including the protective role of metallothionein (MT), is still not fully understood. The aim of the study was to evaluate the degree [...] Read more.

Cadmium (Cd) is an environmental pollutant known to pose a public health issue. The mechanism of Cd toxicity on the uterus, including the protective role of metallothionein (MT), is still not fully understood. The aim of the study was to evaluate the degree of MT-Cd binding in the uterus of rats exposed per os to Cd at daily doses of 0.09, 0.9, 1.8 and 4.5 mg Cd/kg b.w. for 90 days. To assess the permanence of the bond, the rats were observed over long observation periods: 90 and 180 days after termination of exposure. Additionally, uterine concentration of Zn, Cu, Ca, Mg was determined. Cd leads immediately after exposure to a max. 30-fold increase in the concentration of Cd in the uterus, with only small amounts being bound to MT. After 90 days following termination of exposure, and especially after 180 days, an increase in MT-Cd concentration was noted for the three highest doses; even so, the degree of Cd binding by MT was still small. Additionally, the accumulation of Cd in the uterus disturbs the homeostasis of determined essential elements, manifested by a significant increase in Cu concentration and a decrease in Zn, Mg and Ca, especially 180 days after termination of exposure. The obtained results indicate that MT has only a slight protective role in the uterus and that Cd ions may have harmful effects not related to MT: directly on the uterine tissue, and indirectly by disturbing the homeostasis of its essential elements. Full article

(This article belongs to the Special Issue Molecular Research in Uterine Biology and Pathophysiology)

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16 pages, 3393 KiB

Open AccessArticle

Effects of Substance P and Neurokinin A on the Contractile Activity of Inflamed Porcine Uterus

by Marta Brzozowska, Marta Romaniewicz, Jarosław Całka and Barbara Jana

Int. J. Mol. Sci. 2022, 23(21), 13184; https://doi.org/10.3390/ijms232113184 - 29 Oct 2022

Viewed by 1536

Abstract

Disturbances in uterine contractile activity contribute to the development of inflammation, and recent evidence indicates that tachykinins, including substance P (SP) and neurokinin A (NKA), are involved in controlling uterine function. Here, we determined the effect of Escherichia coli (E. coli)-induced [...] Read more.

Disturbances in uterine contractile activity contribute to the development of inflammation, and recent evidence indicates that tachykinins, including substance P (SP) and neurokinin A (NKA), are involved in controlling uterine function. Here, we determined the effect of Escherichia coli (E. coli)-induced inflammation on expression of protein receptor subtypes for substance P (NK1R) and neurokinin A (NK2R) in the pig myometrium as well as their role in contractility of inflamed uterus. The severe acute endometritis developed in the E. coli group and the expression of NK1R and NK2R proteins increased in the myometrium. Compared to the pre-administration period, SP (10⁻⁶ M) reduced the amplitude and frequency in the myometrium of the E. coli group and the amplitude was higher and the frequency was lower versus other groups. NKA reduced the amplitude and increased the frequency in endometrium/myometrium of the E. coli group. In this group, the amplitude was lower and the frequency was higher than in the CON and SAL groups. Our research showed that NK2R (10⁻⁶ M) antagonist application abolished the NKA inhibitory effect on uterine amplitude. The application of the NK1R (10⁻⁵ M) antagonist together with SP revealed that the inhibitory effect of SP on uterine contractility is achieved independently of the NKR1. Additionally, taking into account the fact that NKA shows an inhibitory effect with the use of NK2R on uterine amplitude suggests the possibility of therapeutic use of the antagonist as a drug increasing uterine contractility in inflammation. Full article

(This article belongs to the Special Issue Molecular Research in Uterine Biology and Pathophysiology)

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9 pages, 1296 KiB

Open AccessArticle

Dystocic Labor and Adrenergic and Noradrenergic Neurotransmitters: A Morphological Experimental Study

by Antonio Malvasi, Antonella Vimercati, Ilaria Ricci, Nico Picardi, Ettore Cicinelli, Ioannis Kosmas, Giorgio Maria Baldini and Andrea Tinelli

Int. J. Mol. Sci. 2022, 23(19), 11379; https://doi.org/10.3390/ijms231911379 - 27 Sep 2022

Cited by 6 | Viewed by 1889

Abstract

Authors investigated the catecholaminergic neurotransmitters (chNs) quantitative modifications in pregnant uterine Lower Uterine Segment (LUS) during prolonged labor (PL) with the fetus in an occiput-posterior position (OPP), in occiput transverse position (OTP) and in fetal head asynclitism, all diagnosed by Intrapartum Ultrasonography (IU). [...] Read more.

Authors investigated the catecholaminergic neurotransmitters (chNs) quantitative modifications in pregnant uterine Lower Uterine Segment (LUS) during prolonged labor (PL) with the fetus in an occiput-posterior position (OPP), in occiput transverse position (OTP) and in fetal head asynclitism, all diagnosed by Intrapartum Ultrasonography (IU). The chNs neurotransmitters, particularly adrenaline (or epinephrine-A) and noradrenaline (or norepinephrine-N), were evaluated in LUS fragments sampled during CS of 34 patients undergoing urgent cesarean section (CS) in PL, compared to chNs fibers in the LUS of 36 women submitted to elective CS. All results were statistically analyzed to understand the differences in neurotransmitters morphological analysis by scanning electronic microscopy examination (SEM). The LUS fragments analysis revealed a reduction of A and N fibers in LUS during PL, compared with the expression of A and N fibers in LUS during elective CS. The PL for OPP, the OTP and asynclitism, all positions causing dystocia in labor lead to a reduction in neurotransmitters in LUS, with a uterine vascularization modification and a reduction in the contractility of smooth uterine cells. The A and N neurotransmitters reduction observed in PL negatively interferes with uterine contraction during labor. Full article

(This article belongs to the Special Issue Molecular Research in Uterine Biology and Pathophysiology)

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16 pages, 7960 KiB

Open AccessArticle

Transient and Prolonged Activation of Wnt Signaling Contribute Oppositely to the Pathogenesis of Asherman’s Syndrome

by Xiang Xue, Xiaoli Li, Jinmeng Yao, Xue Zhang, Xu Ren and Shan Xu

Int. J. Mol. Sci. 2022, 23(15), 8808; https://doi.org/10.3390/ijms23158808 - 8 Aug 2022

Cited by 2 | Viewed by 2383

Abstract

Asherman’s Syndrome (AS) is caused by dysfunction of endometrial regenerative ability, which is controlled by adult stem cells and their niche. The Wnt signaling pathway has been demonstrated to be implicated in this process. This study aimed to clarify the relationship between the [...] Read more.

Asherman’s Syndrome (AS) is caused by dysfunction of endometrial regenerative ability, which is controlled by adult stem cells and their niche. The Wnt signaling pathway has been demonstrated to be implicated in this process. This study aimed to clarify the relationship between the Wnt signaling pathway and the progression of AS after initial endometrial damage. Endometria with and without adhesion as well as from the intrauterine devices three months after the surgery were collected to compare the area of fibrosis. The area% of fibrosis did not vary significantly. Significantly higher expression of non-phosphorylated β-catenin, Wnt5a and Wnt7a was identified in the endometria with adhesion. The CD140b⁺CD146⁺ endometrial stem-like cells were present in the endometria with adhesion. Both Wnt5a and Wnt7a promoted stem cell proliferation. However, only Wnt7a preserved stem cell population by stimulating self-renewal. A rat endometrial injury model was established to investigate the effect of the activated Wnt/β-catenin signaling pathway on endometrial healing. We found that a transient activation of the Wnt/β-catenin signaling pathway promoted angiogenesis and increased the number of glands. In conclusion, transient activation of the Wnt/β-catenin signaling pathway during the acute endometrial damage may help the tissue regeneration, while prolonged activation may correlate to fibrosis formation. Full article

(This article belongs to the Special Issue Molecular Research in Uterine Biology and Pathophysiology)

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16 pages, 24353 KiB

Open AccessArticle

Increased Angiogenesis and Lymphangiogenesis in Adenomyosis Visualized by Multiplex Immunohistochemistry

by Marissa J. Harmsen, Arda Arduç, Maaike C. G. Bleeker, Lynda J. M. Juffermans, Arjan W. Griffioen, Ekaterina S. Jordanova and Judith A. F. Huirne

Int. J. Mol. Sci. 2022, 23(15), 8434; https://doi.org/10.3390/ijms23158434 - 29 Jul 2022

Cited by 6 | Viewed by 2304

Abstract

There is evidence for increased angiogenesis in the (ectopic) endometrium of adenomyosis patients under the influence of vascular endothelial growth factor (VEGF). VEGF stimulates both angiogenesis and lymph-angiogenesis. However, information on lymph vessels in the (ectopic) endometrium of adenomyosis patients is lacking. In [...] Read more.

There is evidence for increased angiogenesis in the (ectopic) endometrium of adenomyosis patients under the influence of vascular endothelial growth factor (VEGF). VEGF stimulates both angiogenesis and lymph-angiogenesis. However, information on lymph vessels in the (ectopic) endometrium of adenomyosis patients is lacking. In this retrospective matched case-control study, multiplex immunohistochemistry was performed on thirty-eight paraffin embedded specimens from premenopausal women who had undergone a hysterectomy at the Amsterdam UMC between 2001 and 2018 to investigate the evidence for (lymph) angiogenesis in the (ectopic) endometrium or myometrium of patients with adenomyosis versus controls with unrelated pathologies. Baseline characteristics of both groups were comparable. In the proliferative phase, the blood and lymph vessel densities were, respectively, higher in the ectopic and eutopic endometrium of patients with adenomyosis than in the endometrium of controls. The relative number of blood vessels without α-smooth muscle actinin (α SMA) was higher in the eutopic and ectopic endometrium of adenomyosis patients versus controls. The level of VEGF staining intensity was highest in the myometrium but did not differ between patients with adenomyosis or controls. The results indicate increased angiogenesis and lymphangiogenesis in the (ectopic) endometrium affected by adenomyosis. The clinical relevance of our findings should be confirmed in prospective clinical studies. Full article

(This article belongs to the Special Issue Molecular Research in Uterine Biology and Pathophysiology)

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26 pages, 1867 KiB

Open AccessArticle

Social Isolation Stress Modulates Pregnancy Outcomes and the Inflammatory Profile of Rat Uterus

by Nayara A. Lopes, Erin A. Falkenberg, Camille Wiley, Vaishvi Patel, Jesus Serrano-Lomelin, Xin Fang, Amanda M. Weiler, J. Keiko McCreary, Gerlinde A. S. Metz and David M. Olson

Int. J. Mol. Sci. 2022, 23(11), 6169; https://doi.org/10.3390/ijms23116169 - 31 May 2022

Cited by 6 | Viewed by 2854

Abstract

Prenatal stressors have been linked to adverse pregnancy outcomes; including preterm birth (PTB). Recent work demonstrates that social isolation in mothers represents a silent stressor contributing to PTB risk. Here; we investigate the association of inflammatory and stress markers with PTB risk in [...] Read more.

Prenatal stressors have been linked to adverse pregnancy outcomes; including preterm birth (PTB). Recent work demonstrates that social isolation in mothers represents a silent stressor contributing to PTB risk. Here; we investigate the association of inflammatory and stress markers with PTB risk in Long–Evans rats exposed to social isolation stress (SIS) during preconception and pregnancy across four generations (F0-F3). Gestational length; blood glucose; corticosterone levels; and maternal and offspring weights were assessed in two SIS paradigms: transgenerational (TG) and multigenerational (MG) exposure. Maternal uterine tissues were collected 21 days after the dams gave birth. Exposure to SIS reduced pregnancy lengths in the parental generation and neonatal birth weights in the F1 and F2 generations. Interleukin (IL)-1β (Il1b) mRNA levels increased in F0 animals but decreased in the offspring of both stress lineages. Protein levels of IL-1β decreased in the TG lineage. Corticotrophin-releasing hormone receptor 1 (Crhr1) expression decreased in SIS-exposed F0 animals and increased in the TG-F2 and MG-F1 offspring. Expression of enzyme 11-β hydroxysteroid dehydrogenase-2 (11bHSD2) was enhanced in F1 animals. These findings suggest SIS has adverse consequences on the F0 mothers; but their F1–F3 progeny may adapt to this chronic stress; thus supporting the fetal programming hypothesis. Full article

(This article belongs to the Special Issue Molecular Research in Uterine Biology and Pathophysiology)

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29 pages, 7107 KiB

Open AccessArticle

Integrative Genomic and Transcriptomic Profiling Reveals a Differential Molecular Signature in Uterine Leiomyoma versus Leiomyosarcoma

by Alba Machado-Lopez, Roberto Alonso, Victor Lago, Jorge Jimenez-Almazan, Marta Garcia, Javier Monleon, Susana Lopez, Francisco Barcelo, Amparo Torroba, Sebastian Ortiz, Santiago Domingo, Carlos Simon and Aymara Mas

Int. J. Mol. Sci. 2022, 23(4), 2190; https://doi.org/10.3390/ijms23042190 - 16 Feb 2022

Cited by 15 | Viewed by 3093

Abstract

The absence of standardized molecular profiling to differentiate uterine leiomyosarcomas versus leiomyomas represents a current diagnostic challenge. In this study, we aimed to search for a differential molecular signature for these myometrial tumors based on artificial intelligence. For this purpose, differential exome and [...] Read more.

The absence of standardized molecular profiling to differentiate uterine leiomyosarcomas versus leiomyomas represents a current diagnostic challenge. In this study, we aimed to search for a differential molecular signature for these myometrial tumors based on artificial intelligence. For this purpose, differential exome and transcriptome-wide research was performed on histologically confirmed leiomyomas (n = 52) and leiomyosarcomas (n = 44) to elucidate differences between and within these two entities. We identified a significantly higher tumor mutation burden in leiomyosarcomas vs. leiomyomas in terms of somatic single-nucleotide variants (171,863 vs. 81,152), indels (9491 vs. 4098), and copy number variants (8390 vs. 5376). Further, we discovered alterations in specific copy number variant regions that affect the expression of some tumor suppressor genes. A transcriptomic analysis revealed 489 differentially expressed genes between these two conditions, as well as structural rearrangements targeting ATRX and RAD51B. These results allowed us to develop a machine learning approach based on 19 differentially expressed genes that differentiate both tumor types with high sensitivity and specificity. Our findings provide a novel molecular signature for the diagnosis of leiomyoma and leiomyosarcoma, which could be helpful to complement the current morphological and immunohistochemical diagnosis and may lay the foundation for the future evaluation of malignancy risk. Full article

(This article belongs to the Special Issue Molecular Research in Uterine Biology and Pathophysiology)

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Review

Jump to: Research, Other

13 pages, 1355 KiB

Open AccessReview

Biomechanical Forces Determine Fibroid Stem Cell Transformation and the Receptivity Status of the Endometrium: A Critical Appraisal

by Onder Celik, Nilufer Celik, Nur Dokuzeylul Gungor, Sudenaz Celik, Liya Arslan, Andrea Morciano and Andrea Tinelli

Int. J. Mol. Sci. 2022, 23(22), 14201; https://doi.org/10.3390/ijms232214201 - 17 Nov 2022

Cited by 4 | Viewed by 2384

Abstract

Myometrium cells are an important reproductive niche in which cyclic mechanical forces of a pico-newton range are produced continuously at millisecond and second intervals. Overproduction and/or underproduction of micro-forces, due to point or epigenetic mutation, aberrant methylation, and abnormal response to hypoxia, may [...] Read more.

Myometrium cells are an important reproductive niche in which cyclic mechanical forces of a pico-newton range are produced continuously at millisecond and second intervals. Overproduction and/or underproduction of micro-forces, due to point or epigenetic mutation, aberrant methylation, and abnormal response to hypoxia, may lead to the transformation of fibroid stem cells into fibroid-initiating stem cells. Fibroids are tumors with a high modulus of stiffness disturbing the critical homeostasis of the myometrium and they may cause unfavorable and strong mechanical forces. Micro-mechanical forces and soluble-chemical signals play a critical role in transcriptional and translational processes’ maintenance, by regulating communication between the cell nucleus and its organelles. Signals coming from the external environment can stimulate cells in the format of both soluble biochemical signals and mechanical ones. The shape of the cell and the plasma membrane have a significant character in sensing electro-chemical signals, through specialized receptors and generating responses, accordingly. In order for mechanical signals to be perceived by the cell, they must be converted into biological stimuli, through a process called mechanotransduction. Transmission of fibroid-derived mechanical signals to the endometrium and their effects on receptivity modulators are mediated through a pathway known as solid-state signaling. It is not sufficiently clear which type of receptors and mechanical signals impair endometrial receptivity. However, it is known that biomechanical signals reaching the endometrium affect epithelial sodium channels, lysophosphatidic acid receptors or Rho GTPases, leading to conformational changes in endometrial proteins. Translational changes in receptivity modulators may disrupt the selectivity and receptivity functions of the endometrium, resulting in failed implantation or early pregnancy loss. By hypermethylation of the receptivity genes, micro-forces can also negatively affect decidualization and implantation. The purpose of this narrative review is to summarize the state of the art of the biomechanical forces which can determine fibroid stem cell transformation and, thus, affect the receptivity status of the endometrium with regard to fertilization and pregnancy. Full article

(This article belongs to the Special Issue Molecular Research in Uterine Biology and Pathophysiology)

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14 pages, 2270 KiB

Open AccessReview

Molecular Insights in Uterine Leiomyosarcoma: A Systematic Review

by Radmila Sparić, Mladen Andjić, Ivana Babović, Lazar Nejković, Milena Mitrović, Jelena Štulić, Miljan Pupovac and Andrea Tinelli

Int. J. Mol. Sci. 2022, 23(17), 9728; https://doi.org/10.3390/ijms23179728 - 27 Aug 2022

Cited by 13 | Viewed by 4127

Abstract

Uterine fibroids (UFs) are the most common benign tumors of female genital diseases, unlike uterine leiomyosarcoma (LMS), a rare and aggressive uterine cancer. This narrative review aims to discuss the biology and diagnosis of LMS and, at the same time, their differential diagnosis, [...] Read more.

Uterine fibroids (UFs) are the most common benign tumors of female genital diseases, unlike uterine leiomyosarcoma (LMS), a rare and aggressive uterine cancer. This narrative review aims to discuss the biology and diagnosis of LMS and, at the same time, their differential diagnosis, in order to distinguish the biological and molecular origins. The authors performed a Medline and PubMed search for the years 1990–2022 using a combination of keywords on the topics to highlight the many genes and proteins involved in the pathogenesis of LMS. The mutation of these genes, in addition to the altered expression and functions of their enzymes, are potentially biomarkers of uterine LMS. Thus, the use of this molecular and protein information could favor differential diagnosis and personalized therapy based on the molecular characteristics of LMS tissue, leading to timely diagnoses and potential better outcomes for patients. Full article

(This article belongs to the Special Issue Molecular Research in Uterine Biology and Pathophysiology)

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9 pages, 646 KiB

Open AccessHypothesis

Uterine Fibroids Causing Preterm Birth: A New Pathophysiological Hypothesis on the Role of Fibroid Necrosis and Inflammation

by Emma E. Don, Anadeijda J. E. M. C. Landman, Guus Vissers, Ekaterina S. Jordanova, Emiel D. Post Uiterweer, Christianne J. M. de Groot, Marjon A. de Boer and Judith A. F. Huirne

Int. J. Mol. Sci. 2022, 23(15), 8064; https://doi.org/10.3390/ijms23158064 - 22 Jul 2022

Cited by 6 | Viewed by 5722

Abstract

According to recent studies and observations in clinical practice, uterine fibroids increase the risk of preterm birth. There are several theories on the pathogenesis of preterm birth in the presence of fibroids. One theory proclaims that fibroid necrosis leads to preterm birth, though [...] Read more.

According to recent studies and observations in clinical practice, uterine fibroids increase the risk of preterm birth. There are several theories on the pathogenesis of preterm birth in the presence of fibroids. One theory proclaims that fibroid necrosis leads to preterm birth, though pathophysiological mechanisms have not been described. Necrotic tissue secretes specific cytokines and proteins and we suggest these to be comparable to the inflammatory response leading to spontaneous preterm birth. We hypothesize that fibroid necrosis could induce preterm parturition through a similar inflammatory response. This new hypothesis generates novel perspectives for future research and the development of preventative strategies for preterm birth. Moreover, we emphasize the importance of the recognition of fibroids and especially fibroid necrosis by clinicians during pregnancy. Full article

(This article belongs to the Special Issue Molecular Research in Uterine Biology and Pathophysiology)

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