Age‐dependent phenotypes of ovarian endometriomas

Benagiano, Giuseppe; Guo, Sun‐Wei

doi:10.1002/rmb2.12438

Cited by 6 publications

(4 citation statements)

References 150 publications

(251 reference statements)

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“…It is hypothesized that there is a different mechanism in early-onset endometriosis in pre-menarcheal girls [ 33 ]. The presence of eMSCs in NUB has been thought to be the origin of early-onset endometriosis [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Is neonatal uterine bleeding responsible for early-onset endometriosis?

Ogawa

Khan

Kuroboshi

et al. 2023

Reprod Biol Endocrinol

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Background It has been hypothesized that the origin of early-onset endometriosis could be from endometrial mesenchymal stem cells (eMSCs) in neonatal uterine blood (NUB). There is no information on the possible mechanistic basis linking an association between NUB/neonatal endometrium and development of early-onset endometriosis. In this study we performed a series of experiments to clarify the mechanistic link between NUB and/or neonatal endometrium and development of early-onset endometriosis. Methods We retrospectively collected postmortem neonatal endometria (n = 15) and prospectively collected NUB (n = 18) of female babies for the analysis of different biological markers including eMSCs. Immunohistochemical analysis of neonatal endometria was performed to examine the expression patterns of ovarian steroid receptors (ER/PGR), decidualization (prolactin, IGFBP1), pre-decidualization (Glycodelin A, α-SMA), proliferation (Ki-67 index), vascularity (CD31 + cells), immunocompetent CD68+, CD45+, CD56 + cells and some putative markers of eMSCs. Cell transfer method and immunocytochemistry were used to investigate the eMSCs and/or endometrial cells in NUB. Results Immunohistochemical analysis of postmortem neonatal endometria revealed variable staining response to ER/PGR, decidual markers, and substantial proliferative and angiogenic activity. A moderate to strong immunoexpression of Glycodelin-A was found in both neonatal and adult endometria. The tissue infiltration of CD56+, CD45 + and CD68 + immunocompetent cells was significantly low in neonatal endometria than that in adult endometria (p = 0.0003, p < 0.0001, p = 0.034, respectively). No eMSCs or even endometrial cells were detected in NUB. However, a variable expression of some phenotypes of eMSCs (CD90/CD105) was found in neonatal endometria. Conclusions Based on our serial experiments we did not find any supporting evidence for the role of NUB in early-onset endometriosis. Neonatal endometria showed variable expression of ovarian steroid receptors, decidualization, and a substantial amount of proliferative and angiogenic activity. As an alternative mechanism, a significantly less tissue accumulation of immunocompetent cells in neonatal endometria may explain the survival of ER + and PGR + cells should they make entry into the pelvis and consequent development of early endometriosis with the onset of ovarian function. Future study with large sample size and application of modified technological tools is warranted to test the NUB hypothesis and to clarify their biological or clinical significance. Trial registration not applicable.

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Section: Discussionmentioning

confidence: 99%

Is neonatal uterine bleeding responsible for early-onset endometriosis?

Ogawa

Khan

Kuroboshi

et al. 2023

Reprod Biol Endocrinol

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“…Although pain scores decreased with age, we did not observe an association between age and endometrioma size. Moreover, Benagiano and Guo [ 10 ] reported that the presentation of endometriosis differs with age, suggesting that the pathophysiology of endometriosis may vary with age and may have an impact on pain.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Characteristics of Ovarian Endometriomas in Patients with Endometriosis: Efficacy of a Low-Dose Estrogen/Progestogen Combination

Komatsu,

Sunada,

Endo

et al. 2023

Gynecol Obstet Invest

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Objectives: Approximately 17–44% of women diagnosed with endometriosis have ovarian endometriomas (cysts). Although ovarian endometriomas may adversely affect quality of life and work performance, no reports have been published on the relationship between patient characteristics, cyst size, and pain associated with ovarian endometriomas. The objective of this study was to assess the association between age, cyst size, and pain in women with ovarian endometriomas. Design: Retrospective secondary analysis of pooled data from six randomized clinical trials of the use of low-dose estrogen/progestogen drugs for endometriosis. Participants/Materials, Setting, Methods: Data on 491 patients enrolled in four randomized and two non-randomized trials between 2003 and 2017, who had not undergone surgical treatment prior to trial participation, were pooled. We examined differences in the dysmenorrhea score, menstrual pain score, analgesic score, and visual analog scale (VAS) by age and endometrioma size. Results The mean dysmenorrhea, menstrual pain, and analgesic scores were 4.2, 2.2, and 2.0, respectively. The mean VAS for pelvic pain was 55, which decreased significantly with increasing age. There was no correlation between age and endometrioma size, the dysmenorrhea score and the endometrioma volume or maximum diameter. In addition, there was no correlation between menstrual pain, analgesic score, or VAS and the endometrioma volume or maximum diameter. Limitations The details of past treatment history were not available; therefore, these could not be considered in the analysis. In addition, the assessment of pain is heavily influenced by psychological aspects, making it difficult to assess the true extent of pain. Conclusions Endometrioma size was unrelated to dysmenorrhea or pelvic pain measured using the VAS.

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“…Postmenopausal endometriosis is less active and less extensive than premenopausal endometriosis [ 158 ]. The disease is likely to present as ovarian endometriomas or deep infiltrating endometriosis, and the pattern of superficial peritoneal endometriosis is rarely seen in this age group [ 161 ].…”

Section: Postmenopausal Endometriosis and The Risk Of Malignant Trans...mentioning

confidence: 99%

“…However, these cells remained morphologically benign with no evidence of atypia or malignant transformation [ 168 ]. There is no doubt that time is an essential factor in cancer development, hence postmenopausal endometriosis has a greater predisposition to malignant transformation [ 161 ].…”

Section: Postmenopausal Endometriosis and The Risk Of Malignant Trans...mentioning

confidence: 99%

The “Road” to Malignant Transformation from Endometriosis to Endometriosis-Associated Ovarian Cancers (EAOCs): An mTOR-Centred Review

Hablase,

Kyrou,

Randeva

et al. 2024

Cancers

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Ovarian cancer is an umbrella term covering a number of distinct subtypes. Endometrioid and clear-cell ovarian carcinoma are endometriosis-associated ovarian cancers (EAOCs) frequently arising from ectopic endometrium in the ovary. The mechanistic target of rapamycin (mTOR) is a crucial regulator of cellular homeostasis and is dysregulated in both endometriosis and endometriosis-associated ovarian cancer, potentially favouring carcinogenesis across a spectrum from benign disease with cancer-like characteristics, through an atypical phase, to frank malignancy. In this review, we focus on mTOR dysregulation in endometriosis and EAOCs, investigating cancer driver gene mutations and their potential interaction with the mTOR pathway. Additionally, we explore the complex pathogenesis of transformation, considering environmental, hormonal, and epigenetic factors. We then discuss postmenopausal endometriosis pathogenesis and propensity for malignant transformation. Finally, we summarize the current advancements in mTOR-targeted therapeutics for endometriosis and EAOCs.

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Age‐dependent phenotypes of ovarian endometriomas

Cited by 6 publications

References 150 publications

Is neonatal uterine bleeding responsible for early-onset endometriosis?

Is neonatal uterine bleeding responsible for early-onset endometriosis?

Evaluation of the Characteristics of Ovarian Endometriomas in Patients with Endometriosis: Efficacy of a Low-Dose Estrogen/Progestogen Combination

The “Road” to Malignant Transformation from Endometriosis to Endometriosis-Associated Ovarian Cancers (EAOCs): An mTOR-Centred Review

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