Is neonatal uterine bleeding responsible for early-onset endometriosis?

Kanae Ogawa, Khaleque N Khan, Khaleque Newaz Khan, Haruo Kuroboshi, Akemi Koshiba, Koki Shimura, Tatsuro Tajiri, Shigehisa Fumino, Hiroyuki Fujita, Tomoharu Okubo, Yoichiro Fujiwara, Go Horiguchi, Satoshi Teramukai, Akira Fujishita, Kyoko Itoh, Sun-Wei Guo, Sun‐Wei Guo, Jo Kitawaki, Taisuke Mori
Reproductive biology and endocrinology : RB&E · 2023 · vol. 21(1) , pp. 56 · doi:10.1186/s12958-023-01099-1 · PMID:37337237 · PMC10278367 · W4381137502
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

This study found no evidence of endometrial cells or eMSCs in neonatal uterine blood and suggests low immunocompetent cell accumulation in neonatal endometria may explain early endometriosis development.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-10 ⓘ

Ogawa et al. investigated whether neonatal uterine bleeding (NUB) and/or neonatal endometrium could mechanistically contribute to early-onset endometriosis by hypothesizing that NUB might contain endometrial mesenchymal stem cells (eMSCs) capable of surviving and later differentiating after pubertal estrogen exposure. They performed immunohistochemical analyses of postmortem neonatal endometria (n=15) for ovarian steroid receptors, decidual/pre-decidual markers, proliferation/angiogenesis, and immunocompetent cell infiltration, and they prospectively collected overt NUB (n=18) to look for eMSCs/endometrial cells using immunocytochemistry and cell-transfer approaches; variable ER/PGR signaling and substantial proliferation/angiogenic activity were observed in neonatal endometrium, but no eMSCs or endometrial cells were detected in NUB, and neonatal endometria had significantly lower accumulation of CD56+, CD45+, and CD68+ cells than adult tissue. A limitation explicitly noted is the need for larger sample sizes and improved technologies to further test the NUB hypothesis. This paper is centrally about endometriosis — it directly tests the neonatal uterine bleeding (NUB) hypothesis as a mechanistic origin for early-onset endometriosis and reports no supporting evidence.

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Abstract

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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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometrium Endometrium Endometrium Endometrium

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