endometriosis basic science - prof tz jacoeb

8/10/2019 Endometriosis Basic Science - Prof TZ Jacoeb

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ENDOMETRIOSIS:FROM BASIC SCIENCE TO

CLINICAL APPLICATION

T.Z. Jacoeb

Division of Reproductive Immunoendocrinology

Department of Obstetrics and GynecologyFaculty of Medicine University of Indonesia

Jakarta



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WHAT IS

ENDOMETRIOSIS?

15 September 2012 Endometriosis: Basic Science and Clinical Application 2



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What is endometriosis?

• Endometriosis is the implantation of endometrium-likeglandular and stromal cells outside their normal location in theuterus.

• Varma R, Rollason T, Gupta JK and Maher ER. Endometriosis and the neoplastic process. Reproduction2004;127: 293 –304

• The presence of endometrium-like tissue outside the uterus,

which induces a chronic, inflammatory reaction • Kennedy et al, 2005; Falconer, 2008

• Endometriosis is a chronic benign gynecological diseasecharacterized by the presence of abnormally located tissue(outside the uterine cavity) resembling the endometrium withglands and stroma (endometrial epithelial and stromal cells).

• Zasheva D, Dimitrov R, Stamenova M. Endometriosis and the role of the integrins in the pathogenesis of theendometriosis. Akush Ginekol (Sofiia). 2007;46(5):37-48 .

• Endometriosis is a benign, estrogen-dependent disease withan obscure etiology.

• Contemporary genetic technologies and female reproduction. The Evian Annual Reproduction (EVAR)Workshop Group 2010. Hum. Reprod. Update (November-December 2011) 17 (6): 829-847. doi:10.1093/humupd/dmr033




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What is endometriosis?

• Endometriosis has been considered an enigmatic

„disease‟ because it is often identified when investigating

women with infertility, chronic pelvic pain, dyspareunia

and dysmenorrhea.

• Women with endometriosis have an increased risk of

different types of malignancies, especially ovarian cancer

and non-Hodgkin's lymphoma.

• Contemporary genetic technologies and female reproduction. The Evian Annual Reproduction (EVAR) Workshop

Group 2010. Hum. Reprod. Update (November-December 2011) 17 (6): 829-847. doi: 10.1093/humupd/dmr033




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Basic Sciences Involved in Endometriosis

• Anatomy and Embryology

• Physiology

• Medical Physics

• Biology and MolecularBiology

• Genetics

• Rheology

• Histology, Pathology, andCytology

• Angiology and Angiogenesis

• Biochemistry

• Pharmacology

• Immunology• Reproductive

Immunoendocrinology

• Endocrinology and

Metabolic Diseases• Oncology




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Applied Sciences Involved in

Endometriosis

• Ultrasonography

• Radio-Imaging

• Endoscopy

• Surgery

• Pharmacy

• Informational

Technology

• Bioengineering




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ANATOMY




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Female Genital System




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Typical Locations of Endometriosis Sites




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Blood Supply to the Female Internal Genitalia




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Pathogenesis of Endometriosis

• It is likely to be polygenic and multifactorial, but the exact pathogenicmechanisms are still not entirely clear.

• The most widely accepted theory is that of retrograde menstruation inthe context of:• an abnormal immune response, and

• a genetic predisposition to developing endometriotic lesions;• this possibly occur after exposure to an unidentified environmental factor.

• Sasson and Taylor, 2008.

• Zasheva D, Dimitrov R, Stamenova M. Endometriosis and the role of the integrins in the pathogenesis of the endometriosis. Akush Ginekol (Sofiia). 2007;46(5):37-48.

• A better understanding of the pathogenesis of endometriosis mayhelp to identify new pharmacological targets and facilitate thedevelopment of new treatments.

• Contemporary genetic technologies and female reproduction. The Evian AnnualReproduction (EVAR) Workshop Group 2010. Hum. Reprod. Update (November-December2011) 17 (6): 829-847. doi: 10.1093/humupd/dmr033




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Pathogenesis of Endometriosis

Genetic SusceptibilityEnvironmental Factors

Dioxin

Immunological & Cellular Alterations

ENDOMETRIUM FRAGMENTSAngiogenesis

VEGF

Retrograde

Menstruation

IL-8MCP1

Aromatase

E2




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A theoretical model of the development of endometriosis.

Fauser B et al. Hum. Reprod. Update 2011;17:829-847

© The Author 2011. Published by Oxford University Press on behalf of the European Society of

Human Reproduction and Embryology. For Permissions, please email: [email protected].




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17



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1 S b 2012 E d i i B i S i d Cli i l A li i 18



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15 S t b 2012 E d t i i B i S i d Cli i l A li ti 19



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Critical factors in the pathogenesis of

endometriosis

• Attachment of endometrial cells to the mesothelial cells

• Invasion of endometrial cells into the mesothelium

• Angiogenesis near nascent endometriosis implants

• Proliferation of ectopic endometrial cells

• Recruitment of inflammatory cells that support persistenceof the implants

• Mahutte et.al. In: Olive DL. Endometriosis in Practice (2005:82)




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Obstacles in the Study of Endometriosis

• The study of endometriosis is complicated by a number of factors:

• the presence of different cell types within endometriotic lesions, and

• the involvement of different pathogenic mechanisms in the formation of distinct

types of endometriotic lesion (such as peritoneal, ovarian and rectovaginal)• (Nisolle and Donnez, 1997).

• It may be difficult to distinguish between cause and effect:

• differences in eutopic endometrium between patients with and without

endometriosis, or in eutopic versus ectopic endometrium. • Contemporary genetic technologies and female reproduction. The Evian Annual Reproduction (EVAR)

Workshop Group 2010. Hum. Reprod. Update (November-December 2011) 17 (6): 829-847. doi:

10.1093/humupd/dmr033





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EMBRYOLOGY• Development of Peritoneum• Development of Edometrium





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Three Main Layers in Embryogenesis

• Endoderm

• Mesoderm

• Ectoderm





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The initial stages of human embyogenesis.http://www.digplanet.com/wiki/Human_embryogenesis





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Blastocyst with an inner cell mass and trophoblast.http://www.digplanet.com/wiki/Human_embryogenesis

Nidation and Implantation of Embryo





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Development of female genital organs and tract





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Embryological Development Overview of

Female Genital OrgansDevelopmental Age Feature

Day 28 first primordial germ cells observed

Week 4-7 germ cell proliferation and migration

Week 4-5 (day 28-30) mesonephric tubules form

Week 4-5 (day 28-30) mesonephric ducts (Wolffian) forms

Week 5 (day 31-35)genital ridge forms from coelomic

epithelium thickening

Week 6 (day 35-42) germ cells migrate to dorsal mesentry

Week 6 (day 38-42) budding indifferent gonad

Week 6 (day 40-42)paramesonephric duct (Mullerian)

forms

Week 7 (day 42-48)germ cells migrate into indifferent

gonad

(Table modified from: Kavlock R, Cummings A., 2004. Data originally from Parrott JA, Skinner MK., 1999)





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Development of genital ducts: Indifferent stage

7th week 9th week

p pp 31




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p pp




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Embryology of the Female Genital Tract

Paramesonephric ducts

(Müllerian ducts)

http://embryology.med.unsw.edu.au/notes/genitalxxuterus.htm#Movies

Müllerian refers to Johannes Peter Müller (1801-1858) a German scientist who specialized in comparative anatomy.

He was the first in 1830 to described the duct named after him, the "Müllerian duct" also called the paramesonephric duct.

Two paramesonephric ducts form from coelomic

epithelium extending beside the mesonephric ducts.

These ducts initially form and then degenerate in the

male.

In the absence of Müllerian Inhibitory Factor theseducts proliferate and grow extending from the vaginal

plate on the wall of the urogenital sinus to lie beside

the developing ovary.

The paired ducts begin to fuse from the vaginal plate

end, forming the primordial body of the uterus and theunfused lateral arms form the uterine tubes.

p pp




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Early Fetal Structure


The Müllerian duct (=

paramesonephric duct, preferred

terminology) paired ducts that form

the epithelial lining of female

reproductive organs: uterine tube,uterus, upper vaginal canal.

The term "paramesonephric" duct

means beside the mesonephric

(Wolffian) duct, which is itsanatomical location in early

development.Urogenital sinus of female human embryo of 8.5 to 9 weeks old(From model by Keibel) (Image: Gray's Anatomy)

p pp




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Drews U, Sulak O, Schenck PA. Androgens and the development of the vagina. Biol Reprod. 2002 Oct;67(4):1353-9.

PMID: 12297555)




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Genital duct development in female

• Paramesonephric ducts develop into the main genitalducts

• Initially 3 parts can berecognized in each duct:

Cranial vertical portion thatopens into the abdominalcavity....develop into uterinetube

Horizontal part that crossesthe mesonephricduct...develop into uterine

tubeCaudal vertical part that

fuses with its partner fromthe opposite side...fuse toform uterine canal




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• A recent study using both chicken and mouseembryos has shown that these initially paired tubular

structures derive from the coelomic epithelium.

• Müllerian ducts have three elements:

1) a canalized epithelial tube2) mesenchymal cells surrounding the tube

3) coelomic epithelial cells.


Guioli S, Sekido R, Lovell-Badge R. The origin of the Müllerian duct in chick and mouse. Dev Biol. 2006 Oct 3


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17070514&dopt=Abstract

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17070514&dopt=Abstract



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Vagina Development

• The vagina arising by downward growth of Wolffian and

Müllerian ducts.

• The sinovaginal bulbs are the caudal ends of the

Wolffian ducts.• Vaginal development is also under negative control of

androgens.




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Development of the peritoneum

• The peritoneum develops ultimately from the mesoderm

of the trilaminar embryo.

• As an embryo develops, the various abdominal organs

grow into the abdominal cavity from structures in the

abdominal wall.

• In this process they become enveloped in a layer of

peritoneum.




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Peritoneum

• Parietal peritoneum:

• lines the inner surfaces of the walls of the abdominopelvic cavity

peritoneum.

• has same a/v/n/lymphatics, as the region of wall that it covers

• is sensitive to pressure, pain, heat+ cold+ laceration.

• Visceral peritoneum:

• lies on the surfaces of the abdominal and pelvic organs.

• covers visceral organs like the stomach and intestines.

• has same a/v/n/lymphatics, as the organ it covers.• stimulated primarily by stretching and chemical irritation.

• http://anatomy.uams.edu/anatomyhtml/peritoneum.html




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ENDOMETRIUM




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Graph illustrating the Noyes method of endometrial dating, which highlights the uncertainty

in timing introduced during the post-ovulatory period, the mid-luteal phase and by measuring

the LH surge.

Diedrich K et al. Hum. Reprod. Update 2007;13:365-377


Human Reproduction and Embryology. All rights reserved. For Permissions, please email:

[email protected]




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The roles of progesterone and estrogen (E2; E3, estriol) and estrogen receptors (ER) during

endometrial development.



Human Reproduction and Embryology. All rights reserved. For Permissions, please email:

[email protected]




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Factors regulated during the early stages of implantation.



Human Reproduction and Embryology. All rights reserved. For Permissions, please email: [email protected]




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GENETICS, HORMONAL, AND

IMMUNOLOGICAL ASPECTS



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Genetics of endometriosis

• First degree relatives of patients with endometriosis have a 6.9%

incidence of endometriosis in comparison with a 1% risk in controls.

• Susceptibility to endometriosis has focused mainly on genes involved

in inflammation, steroid hormone regulation, metabolism,

biosynthesis, detoxification, vascular function and tissue remodelling.

• Specific miRNAs have a function in the pathophysiology of

endometriosis.• Contemporary genetic technologies and female reproduction. The Evian Annual

Reproduction (EVAR) Workshop Group 2010. Hum. Reprod. Update (November-

December 2011) 17 (6): 829-847. doi: 10.1093/humupd/dmr033



Endometriosis: Basic Science and Clinical Application 50



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Attar E and S.E. Bulun, Hum Reprod Update.2005; 0: 341

Aromatase Inhibitors: complete inhibition in estrogen synthesis

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Endometriosis: immunologic abnormality

Systemic

• Increased immunoglobulin production

• Increased in T-helper (CD4 ) cells

• Lymphocyte-mediated cytotoxicity deficiency to the

endometrium

• Embryotoxic serum

• Suppressing serum to the NK cell activity

• Cellular immunity deficiency

• Defect in NK cell activity

• Abnormal autoimmune function

• Decrease in suppressor cell activity



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FETAL ENDOMERIOSIS




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Müllerianosis and Fetal Endometriosis

• Sampson's classification of heterotopic or misplaced

endometrial tissue is based on pathogenesis:

1. direct invasion or primary endometriosis [adenomyosis];

2. a similar condition occurs in the wall of the tube from its invasion

by the tubal mucosa [endosalpingiosis];3. peritoneal or implantation endometriosis;

4. transplantation endometriosis;

5. metastatic endometriosis;

6. developmentally misplaced endometrial tissue [Müllerianosis]

(Sampson, 1925).

• Batt RE, Smith RA, Buck Louis GM, Martin DC, Chapron C, Koninckx

PR, Yeh J. Müllerianosis. Histol Histopathol. 2007 Oct;22(10):1161-6.




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• Müllerianosis may be defined as an organoid structure of

embryonic origin.

• A choristoma composed of Müllerian rests – (normal

endometrium, normal endosalpinx, and normal

endocervix) - singly or in combination, incorporated withinother normal organs during organogenesis.

• A choristoma is a mass of histologically normal tissue that

is "not normally found in the organ or structure in which it

is located” (Choristoma, 2006).

• Batt RE, Smith RA, Buck Louis GM, Martin DC, Chapron C, Koninckx PR, Yeh J.

Müllerianosis. Histol Histopathol. 2007 Oct;22(10):1161-6.




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• Müllerian choristomas are a subset of non-Müllerian

choristomas found throughout the body.

• Histologically, endometrial-Müllerianosis and

endometriosis are both composed of endometrial glands

and stroma, but there the similarity ends. Their

pathogenesis is different.

• Batt RE, Smith RA, Buck Louis GM, Martin DC, Chapron C,Koninckx PR, Yeh J. Mülleriano sis . Histol Histopathol. 2007

Oct;22(10):1161-6.




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• Researchers remain unsure as to the definitive cause of

endometriosis.

• Theory of Müllerianosis for endometriosis, that is the

misplacing of primitive endometrial tissue along the

migratory pathway of fetal organogenesis.• Signorile PG, Baldi F, Bussani R, D'Armiento M, De Falco M, Baldi A.

Ectopic endometrium in human fetuses is a common event and sustains

the theory of müllerianosis in the pathogenesis of endometriosis, a

disease that predisposes to cancer. J Exp Clin Cancer Res. 2009 Apr

9;28:49


http://www.ncbi.nlm.nih.gov/pubmed/19358700




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• Autopsy 36 human female fetuses at different gestational age.• Morphological and immunohistochemical study (expression of estrogen

receptor and CA125) on the pelvic organs of the 36 fetuses included en-blockand totally analyzed.

• In 4 out of 36 fetuses we found presence of misplaced endometrium in fivedifferent ectopic sites, in the:

• recto-vaginal septum,• proximity of the Douglas pouch,

• mesenchimal tissue close to the posterior wall of the uterus,

• rectal tube at the level of muscularis propria, and

• wall of the uterus. All these sites are common location of endometriosis in women.

• A cause of endometriosis is proposed as the dislocation of primitive

endometrial tissue outside the uterine cavity during organogenesis.• Signorile PG, Baldi F, Bussani R, D'Armiento M, De Falco M, Baldi A. Ectopic

endometrium in human fetuses is a common event and sustains the theory ofmüllerianosis in the pathogenesis of endometriosis, a disease that predisposesto cancer. J Exp Clin Cancer Res. 2009 Apr 9;28:49






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COELOMIC METAPLASIA AND

ADHESION MOLECULES




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Rokitansky Endometriosis = Coelomic

Metaplasia• Retrograde menstruation required the existence of a uterine

structure and endometrial tissue.

• A 20-year-old with Mayer-Rokitansky-Küster-Hauser syndromepresented with increasing pelvic pain and underwentlaparoscopy.

• Uterine, cervical, vaginal, and tubal agenesis was confirmed.• Stage I endometriosis was visualized in the posterior cul-de-sac anddestroyed.

• She received medical therapy for 5 years until she represented withpain and underwent another laparoscopy, at which endometriosis wasagain identified and destroyed.

• This case of endometriosis in a patient with complete uterineagenesis supports the theory of coelomic metaplasia.• Mok-Lin EY, Wolfberg A, Hollinquist H, Laufer MR. Endometriosis in a

Patient with Mayer-Rokitansky-Küster-Hauser Syndrome and CompleteUterine Agenesis: Evidence to Support the Theory of Coelomic Metaplasia.J Ped Adolescent Gynecol. 2010;23 (1 ): e35-e37


http://www.jpagonline.org/issues?issue_key=S1083-3188(09)X0008-2

http://www.jpagonline.org/issues?issue_key=S1083-3188(09)X0008-2



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Adhesion Molecules in Endometriosis

• A dynamic relationship between the endometrium and

peritoneum because both tissues may participate in the

spontaneous development of endometriosis.

• Various adhesion molecules, pro-inflammatory cytokines

and chemoattractants cytokines have emerged as centralcoordinators of endometrial-peritoneal interactions.

• Kyama CM, Mihalyi A, Simsa P, Falconer H, Fulop V, Mwenda JM,

Peeraer K, Tomassetti C, Meuleman C, D'Hooghe TM. Role of cytokinesin the endometrial-peritoneal cross-talk and development of

endometriosis. Front Biosci (Elite Ed). 2009 Jun 1;1:444-54.






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Adhesion Molecules in Endometriosis

• Menstrual endometrium has the ability to bond and invadethe peritoneal tissue.

• In baboons intrapelvic injection of menstrual endometrium

permits the study of early endometrial-peritoneal

interaction in an in vivo culture microenvironment and canlead to important insight in the early development of

endometriotic lesions.

• Kyama CM, Mihalyi A, Simsa P, Falconer H, Fulop V, Mwenda JM,

Peeraer K, Tomassetti C, Meuleman C, D'Hooghe TM. Role ofcytokines in the endometrial-peritoneal cross-talk and development

of endometriosis. Front Biosci (Elite Ed). 2009 Jun 1;1:444-54.





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Integrins in the Pathogenesis of

Endometriosis• Cell surface receptors with glycoprotein structure.

• Have part in process of adhesion of the endometrial cells

to the proteins from extra-cellular matrix (ECM) outside

the uterus.

• Have part like signal molecules in the processes ofproliferation and invasion of endometrial implants.

• Very essential molecules influencing the viability of

endometrial implants as well as the angiogenesis in the

new forming endometrial implants.

• Zasheva D, Dimitrov R, Stamenova M. Endometriosis and the role of the

integrins in the pathogenesis of the endometriosis. Akush Ginekol (Sofiia).

2007;46(5):37-48.




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Matrix Metalloproteinase in Endometriosis

• Participate in the histologic changes of the endometriumduring the menstrual cycle

• Higher expression during the menstrual and proliferative

phase of the endometrium

• Decreased expression during the secretory phase.

• Degradation of extracellular matrix is essential for the

endometrial cells to invade the peritoneum and to develop

an endometriotic lesion as well.

• Pitsos M, Kanakas N. The role of matrix metalloproteinases in the

pathogenesis of endometriosis. Reprod Sci. 2009 Aug;16(8):717-26.

Epub 2009 Apr 7.




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MALIGNANT POTENCY OFENDOMETRIOSIS

Cli i th l i l i il iti f




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Clinicopathological similarities of

endometriosis and cancer• (i) endometriotic implants may directly undergo malignant

transformation, perhaps through an atypical

endometriosis transition phase;

• (ii) both endometriosis and cancer share common

antecedent mechanisms and/or predisposing factors (e.g.genetic susceptibility, immune/ angiogenic dysregulation,

environmental toxin exposure), with obvious divergence in

molecular pathways downstream.




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Malignant Potencies of Endometriosis:

Histopathology

• Endometriosis displays features of:• Atypia,

• Adherence,

• Invasion and

• Metastases.

• Atypical endometriosis:

• endometrial glands with cytological or architectural atypia

• (LaGrenade & Silverberg 1988),

• observed in 12 –35% of ovarian endometriosis

• (Seidman 1996, Nishida et al. 2000, Bayramoglu & Duzcan 2001).




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Malignant Potencies of Endometriosis:

Histopathology

• 60 –80% of cases of endometriosis-associated ovariancancer (EAOC) occur in the presence of atypical ovarian

endometriosis.• (Fukunaga et al. 1997, Ogawa et al. 2000, Oral et al. 2003).

• 25% show direct continuity of the atypical ovarianendometriosis with ovarian cancer.

• (Fukunaga et al. 1997)




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Malignant Potencies of Endometriosis: Ovarian malignancy may

arise directly from ovarian endometriosis

• Around 60% of EAOCs (endometriosis-associated ovariancancer) occur with the cancer adjacent to endometriosis

or arising directly from ovarian endometriosis, with the

remaining 40% occurring with distant endometriotic

disease• (Erzen & Kovacic 1998, Modesitt et al. 2002).

• Clear-cell and endometrioid carcinomas are the

commonest EAOCs with ovarian endometriosis, whileclear-cell adenocarcinoma and adenosarcoma are the

commonest EAOCs in extra-ovarian endometriosis• (Erzen & Kovacic 1998, Stern et al. 2001, Zaino et al. 2001).



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CLINICAL PRESENTATIOSOF ENDOMETRIOSIS




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3 Clinical Forms of Pelvic Endometriosis

• 1) peritoneal endometriosis,• 2) ovarian endometriosis,

• 3) rectovaginal septum endometriosis.

• These three entities are distinct and have a differenthistopathogenesis (Nisolle, 1996).



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Endometriosis manifestation [1]

Vesicle

Spider nevi

Ecchymosis

Light brown



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Yellowish brown

Red vesicle

Dark red

Laser-cystectomy

Endometriosis manifestation [1]

Th t f d t i l d t i i




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Three types of deep rectovaginal endometriosis

(Adamyan classification, 1993)

1) Retrocervical endometriosis (in which the rectum isusually free of disease)

2) Rectovaginal septum

3) Bowel endometriosis (with infiltrative characteristics

over the bowel thickness)• This type of classification may be more compatible with the

surgical approach of this disease




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Types of deep retrocervical endometriosis

(Adamyan and Martin classification, 2001)




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Types of deep retrocervical endometriosis





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Types of deep rectovaginal endometriosis

(Adamyan classification, 1993)



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Basics of treatment for Pelvic

Endometriosis: Basic Science and Clinical Application 86



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Basics of treatment for Pelvic

endometriosis:

• All foci have to be eliminated: destruction of

tissue, cytoreduction (‘benign cancer’), elimination

of antigen.

• There is no single method of treatment for all type

of endometriosis: medical (hormonal) and surgical

intervention are always necessary.

• Operative laparoscopy is the current choice:clean, less traumatic, prompt recovery.




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Classic Medical Treatments of Endometriosis

Intracrine and Rational Treatment of




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Intracrine and Rational Treatment of

Endometriosis

A = Androgen Arom = aromataseE1 = Estron E2 = EstradiolGnRHa= GnRH agonist

Th ti l di l t t t




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The optimal medical treatment No menopausal symptoms

No proliferation

Menopausal

SymptomsProliferation of implants

Estradiol level

pg/ml

TherapeuticWindow




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Lunenfeld on Endometriosis

• “........back in 1958, I wasn‟t working on implantation onlyto prevent pregnancies; I also wanted to study

implantation because I wanted to prevent metastasis

implanting anywhere in the body”

• Six years later in Chicago when he met Professor Melvyn Cohen, whowas doing the first laparoscopies and showed him endometriotic tissue

in the pelvis, Lunenfeld commented:

• “Listen! This is a very interesting thing, maybe we should

work on implantation and then we could probably prevent

implantation of endometriosis wherever it comes from?”




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Lunenfeld on Endometriosis

• I am sure that working on factors which can controlangiogenesis and factors which can prevent implantation

have a future.

• We are learning to control pain through certain

progestogen agents and GnRH analogues, … but for thetime being the only thing that we really have, and which

really works, is surgical removal of the disease.

• Through laparoscopy you can diagnose and treat at the

same time, removing lesions as good as you can.• But it is still surgery and I only hope in the very near future

endometriosis can be treated medically”.




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FUTURE TREATMENT OFENDOMETRIOSIS




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Stem Cells in Endometriosis

• Adult stem cells have been identified in several tissues,including the endometrium.

• These cells are probably involved in the regenerative

ability of the endometrial cycle, and also in the

pathogenesis of proliferative gynecological diseases, suchas endometriosis.

• Flávia R. Oliveira, Cynthia Dela Cruz, Helen L. Del Puerto, Quésia

T.M.F. Vilamil, Fernando M. Reis and Aroldo F. Camargos. Stem cells:

Are they the answer to the puzzling etiology of endometriosis? Histol

Histopathol 27, 23-29 (2012)



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Stem cells in Endometriosis: a new perspective

• Human endometrium can be reconstructed inimmunodeficient mice upon injection with human

endometrial SP cells• (Cervelló et al., 2010).

• The retrograde menstruation of SP cells and subsequent

implantation onto the surface of ectopic sites are

responsible for the establishment of endometriotic lesions• (Sasson and Taylor, 2008; Masuda et al., 2010).




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Stem cells in Endometriosis: a new perspective

• An initial genetic mutation may cause aberrant behavior ofa subpopulation of endometrial stem cells;

• Clonal expansion of such cells may then occur and result

in development of endometriosis.

• Peritoneal cells could undergo de-differentiation back toendometrial cells, which take on an altered activity.

• (Gargett et al ., 2009).




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Summary

• Endometriosis is an enigmatic disease.• It can emerge at the earliest time in the fetal life.

• The knowledge of human implantation and

embryogenesis is a coined and basic science to

understand the pathogenesis of endometriosis.

• Stem cell is expected to be the future therapy of

endometriosis.




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THANK YOU

©T.Z. Jacoeb15 September 2012

endometriosis basic science - prof tz jacoeb

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