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EVIDENCE FOR GENETIC SIGNATURE OF ADENOMYOSIS / ENDOMETRIOSIS :
First report of adenomyosis in monozygotic twin fetuses
SEUD, 2015
J.Martinovic, D. Rambaud, J. Gogusev, C. Bergeron, A.Benachi
Fetal Pathology Department Hôpital Antoine Béclère
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ENDOMETRIOSIS: BACKGROUND
* affects approx. 10% of the female population * F increases up to 35-60% in women with pain
and/or infertility * one of the most common human diseases * still unknown etiology
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ENDOMETRIOSIS: PATHOGENESIS
• Retrograde menstruation implants (Sampson, 1927) • Vascular migration of endometrium (Sampson,
1927) • Metaplastic theory (Nissole, 1997) • Defects of embryogenesis (Signorille, 2010) • Circulating stem cells’ ectopic impl. (Gargett, 2014)
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ENDOMETRIOSIS: PATHOGENESIS
Sampson’s classification of heterotopic endometrial tissue :
1) direct or primary endometriosis [adenomyosis] 2) peritoneal or implantation endometriosis 3) transplantation endometriosis 4) metastatic endometriosis 5) developmentally misplaced endometrial tissue
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ENDOMETRIOSIS: PATHOGENESIS
• Retrograde menstruation implants (Sampson, 1927) • Vascular migration of endometrium (Sampson,
1927) • Metaplastic theory (Nissole, 1997) • Defects of embryogenesis (Signorille, 2010) • Circulating stem cells’ ectopic impl. (Gargett, 2014)
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ENDOMETRIOSIS: PATHOGENESIS
• Retrograde menstruation implants (Sampson, 1927) • Vascular migration of endometrium (Sampson,
1927) • Metaplastic (coelomic) theory (Nissole, 1997) • Defects of embryogenesis (Signorille, 2010) • Circulating stem cells’ ectopic impl. (Gargett, 2014)
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ENDOMETRIOSIS: PATHOGENESIS
• Retrograde menstruation implants (Sampson, 1927) • Vascular migration of endometrium (Sampson,
1927) • Metaplastic (coelomic) theory (Nissole, 1997) • Defects of embryogenesis (Signorille, 2010) • Circulating stem cells’ ectopic impl. (Gargett, 2014)
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ENDOMETRIOSIS: PATHOGENESIS
• Retrograde menstruation implants (Sampson, 1927) • Vascular migration of endometrium (Sampson,
1927) • Metaplastic (coelomic) theory (Nissole, 1997) • Defects of embryogenesis (Signorille, 2010) • Circulating stem cells’ ectopic impl. (Gargett, 2014)
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ENDOMETRIOSIS: Prospective study
• * designed in 2000 • * informed, written consents for research • * cohort : TOPs, IUFDs • * 420 serial histological serial sections of fetal uteri • * GA: 18-37,4w • * 10 cases (2,4%) of adenomyosis
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ENDOMETRIOSIS: Prospective study : Clinical features
K
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a, b, c : EMA d, e: RO f: RP
X1,6 X 10 X 20
X 10 X 10 X 10
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a, b: EMA c: SMA d: RO
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ADENOMYOSIS: MZ twins
• TTTS / IUFD @ 28w • G2P1, 29 year-old
FP examination: • MCDA placenta TTTS concordant: * 1AVA (J2 J1) * unequal sharing (J1>J2) * vellamentous cord of J2 • No visceral malformations
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ADENOMYOSIS: MZ twins
HES, x0,5 HES, x0,5
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ADENOMYOSIS: MZ twins
HES, x0,5 HES, x0,5
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ADENOMYOSIS: MZ twins
HES, x10 HES, x10
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FETAL ADENOMYOSIS: Conclusion
• In our series of 420 fetal uteri: 2,4% of ectopic endometrial glands • Confirmation of previous reports (4/36 Signorille 2009; 1/13 Signorille 2010, 4/52 Signorille 2011) *Study design / understimated F of adenomyosis
• Concept of fetaly established pre-endometriotic lesions in some cases+++
• Ontogenesis hypothesis: *Aberrant epithelium-mesenchyme signaling dialogue (transition) leading to erroneus endometrial displacement during histogenesis *Aberrant migration of the Mullerian ducts : spreading of cells in the migratory pathway of fetal organogenesis across the physiological bounderies (ie neuronal over migration in CDG disorders )
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FETAL ADENOMYOSIS: Conclusion
*Genetic determination of fetal adenomyosis?
• First report of identical lesions in MZ twin fetuses * Genetic control of endometriosis already suggested on twins’ studies (Hadfield et al., 1997; Kennedy et al., 1996) * high penetrance of adenomyosis/endometriosis gene(s)? • Ongoing study…
• Recent introduction of new genomic tools (NGS) will certainly enhance unravelling of adenomyosis / endometriosis puzzle in the foreseable future
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THANK YOU! :