A View on Uterine Leiomyoma Genesis through the Prism of Genetic, Epigenetic and Cellular Heterogeneity

Koltsova, Alla S.; Efimova, Olga A.; Pendina, Anna A.

doi:10.3390/ijms24065752

IJMS

2023

DOI: 10.3390/ijms24065752

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A View on Uterine Leiomyoma Genesis through the Prism of Genetic, Epigenetic and Cellular Heterogeneity

Alla S. Koltsova

Olga A. Efimova

Anna A. Pendina

Abstract: Uterine leiomyomas (ULs), frequent benign tumours of the female reproductive tract, are associated with a range of symptoms and significant morbidity. Despite extensive research, there is no consensus on essential points of UL initiation and development. The main reason for this is a pronounced inter- and intratumoral heterogeneity resulting from diverse and complicated mechanisms underlying UL pathobiology. In this review, we comprehensively analyse risk and protective factors for UL development, UL cellular … Show more

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Cited by 4 publications

References 360 publications

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Bipedalism and the dawn of uterine fibroids

Vilos,

Burbank

2024

Human Reproduction

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The high prevalence and burden of uterine fibroids in women raises questions about the origin of these benign growths. Here, we propose that fibroids should be understood in the context of human evolution, specifically the advent of bipedal locomotion in the hominin lineage. Over the ≥7 million years since our arboreal ancestors left their trees, skeletal adaptations ensued, affecting the pelvis, limbs, hands, and feet. By 3.2 million years ago, our ancestors were fully bipedal. A key evolutionary advantage of bipedalism was the freedom to use hands to carry and prepare food and create and use tools which, in turn, led to further evolutionary changes such as brain enlargement (encephalization), including a dramatic increase in the size of the neocortex. Pelvic realignment resulted in narrowing and transformation of the birth canal from a simple cylinder to a convoluted structure with misaligned pelvic inlet, mid-pelvis, and pelvic outlet planes. Neonatal head circumference has increased, greatly complicating parturition in early and modern humans, up to and including our own species. To overcome the so-called obstetric dilemma provoked by bipedal locomotion and encephalization, various compensatory adaptations have occurred affecting human neonatal development. These include adaptations limiting neonatal size, namely altricial birth (delivery of infants at an early neurodevelopmental stage, relative to other primates) and mid-gestation skeletal growth deceleration. Another key adaptation was hyperplasia of the myometrium, specifically the neomyometrium (the outer two-thirds of the myometrium, corresponding to 90% of the uterine musculature), allowing the uterus to more forcefully push the baby through the pelvis during a lengthy parturition. We propose that this hyperplasia of smooth muscle tissue set the stage for highly prevalent uterine fibroids. These fibroids are therefore a consequence of the obstetric dilemma and, ultimately, of the evolution of bipedalism in our hominin ancestors.

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Bipedalism and the dawn of uterine fibroids

Vilos,

Burbank

2024

Human Reproduction

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Vaginal leiomyoma in a goat expressing the nuclear progesterone receptor (PGR): a case report

Trzebiatowski,

Kowalewski,

Schmid

et al. 2024

BMC Vet Res

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Background The risk of developing tumorous diseases in the genital tract also increases with age in animals. One of the classified tumor types is genital leiomyoma. Presently, our understanding of the pathogenesis of this tumor in goats is, however, limited. This accounts also for the information regarding the presence of steroid hormone receptors and, thus, possible responsiveness to circulating steroids. Case presentation This study describes the case of a vaginal tumor in a seven-year-old Anglo-Nubian goat. The goat was presented due to blood mixed vaginal discharge. Per vaginal examination a singular pedunculated mass in the dorsum of the vagina measuring approximately 3 cm x 4 cm x 4 cm was revealed. After administering epidural anesthesia, the mass was removed electrothermally. There were no postoperative complications. The histopathological examination identified the mass as a leiomyoma. The immunohistochemical examination revealed the presence of the nuclear progesterone receptor (PGR) in the tumor tissue. One year after the surgery, during the follow-up examination, the goat was in good overall health, and the owners had not observed any recurrence of vaginal discharge. Conclusions When observing vaginal discharge in goats, it is important to consider the possibility of genital tract tumors. These tumors may express sex steroid receptors. In the future, it is worth considering the investigation of potential approaches for preventing tumorigenesis or treating the tumor, such as castration or the administration of antiprogestogens.

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Differential effect of estrogen and progesterone on <i>in vitro</i> growth of uterine leiomyoma cells with chromosome 7 deletions

Koltsova,

Efimova,

Baranov

et al. 2024

Ecological genetics

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Background: The studies on how sex steroid hormones affect growth of uterine leiomyoma (UL) cells with chromosomal abnormalities is highly relevant for development of personalized tumor therapy. Aim: To study in vitro the isolated and combined effects of estrogen and progesterone on UL cells with chromosomal aberrations deletions in 7q. Materials and Methods: The study was performed on 15 ULs, excised from 15 women of 26-44 years of age who were not treated with hormones. UL cells were cultured in hormone-free medium, in the medium supplemented with estrogen, progesterone or both hormones. The chromosome preparations were made and stained with QFH/AcD to perform conventional karyotyping and fluorescence in situ hybridization (FISH) to accurately describe chromosomal rearrangements. The frequency of UL cells with chromosomal aberrations was assessed by interphase FISH. Results: Deletions in 7q were identified in 6 out of 15 karyotyped ULs; four of them had one clone with deletion in 7q whereas two others comprised two clones with 7q deletions of different length. The frequency of cells carrying deletions in 7q greatly varied in UL samples cultured in hormone-free medium: from 3.5 to 93.6 %. Exposure of cell cultures to estrogen and progesterone resulted in a fold change frequency increase in some of the ULs and decrease in the others. The most significant changes in the frequency of cells with deletions in 7q were registered in response to the isolated estrogen and, to a lesser extent, to progesterone exposure; less significant changes were observed after combined hormonal effect. Conclusions: In ULs with deletions in 7q, the frequency of abnormal cells may either increase or decrease in response to estrogen and progesterone in vitro supplementation. The isolated effect of estrogen or progesterone on the frequency of UL cells with deletion in 7q is more pronounced compared to the combined one.

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A View on Uterine Leiomyoma Genesis through the Prism of Genetic, Epigenetic and Cellular Heterogeneity

Cited by 4 publications

References 360 publications

Bipedalism and the dawn of uterine fibroids

Bipedalism and the dawn of uterine fibroids

Vaginal leiomyoma in a goat expressing the nuclear progesterone receptor (PGR): a case report

Differential effect of estrogen and progesterone on <i>in vitro</i> growth of uterine leiomyoma cells with chromosome 7 deletions

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