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Anticoagulant heparan sulfates in female reproduction

- New functions for anticoagulant heparan sulfates in female reproduction : study of the mechanism involved in ovulation and in placentation

Major tissue remodeling occurs in hormone-responsive tissues of the female genital tract, at ovulation and during gestation, involving proteolysis and tightly controlled inflammation. Disorders of tissue remodeling events are associated with female infertility in women with ovarian dysfunction and with gestational pathologies as pre-eclampsia.

Like heparin, anticoagulant heparan sulfate proteoglycans (aHSPG) bind and activate the coagulation inhibitor antithrombin III (AT). aHSPG are present in the vasculature and in the genital tract. The role of aHSPG in reproduction is demonstrated by the reduced fertility of mice harbouring an inactivated gene of 3-O-sulfotransferase, a key synthetic enzyme of aHSPG. These aHSPG deficient mice display multiple reproductive phenotypes, in the female ovulation is defective and gestation is hampered by inflammation around the placenta.

Beyond their anticoagulant activity in the vascular bed, aHSPG seem to play novel and unsuspected functions in the reproductive system. Ovulation and placenta development during gestation require extensive tissue remodeling. aHSPG seem to be involved in the control of the limited inflammation associated to this remodeling and the aim or our current research is to establish the mechanism of aHSPG action and to determine which inflammation mediators are involved in this process (AT, cytokines). We use in vivo transgenic mice models as well as cell culture models (murine and human ovarian, uterine and trophoblastic cells). These models are manipulated by hormones and inflammation mediators to reveal the action mechanism of aHSPG.

Recognition of the importance of aHSPG in reproductive physiology should allow to better understand the pathologies linked to the control of hemostasis and inflammation in the context of tissue remodeling during ovulation and gestation.

Group's publications

Removal of spermatozoa with externalized phosphatidylserine from sperm preparation in human assisted medical procreation: effects on viability, motility and mitochondrial membrane potential.
REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY
2009 vol. 8 pp. 1-1
DE VANTERY ARRIGHI C, LUCAS H, CHARDONNENS D, DE AGOSTINI A

Human follicular fluid heparan sulfate contains abundant 3-O-sulfated chains with anticoagulant activity.
JOURNAL OF BIOLOGICAL CHEMISTRY
2008 vol. 283(42) pp. 28115-28124
DE AGOSTINI A AND AL

An unexpected role for anticoagulant heparan sulfate proteoglycans in reproduction
SWISS MEDICAL WEEKLY
2006 vol. 136(37-38) pp. 583-590
DE AGOSTINI ARIANE

The majority of anticoagulant heparan sulfate is not absolutely essential for normal hemostasis
JOURNAL OF CLINICAL INVESTIGATION
2003 vol. 111 pp. 989-999
HAJMOHAMMADI S., ENJOI K., PRINCIVALLE M., CHRISTI P., LECH M., BEELER D., RAYBURN H., SCHWARTZ J.J., BARZAGAR S., DE AGOSTINI ARIANE, POST M.J., ROSENBERG R.D., SHWORAK N.W.

Coordinate expression of anticoagulant heparan sulfate proteoglycans and serine protease inhibitors in the rat ovary: a potent system of proteolysis control
BIOLOGY OF REPRODUCTION
2002 vol. 66 pp. 144-158
HASAN S, HOSSEINI G, PRINCIVALLE M, DONG JC, BIRSAN D, CAGIDE C, DE AGOSTINI A

Anticoagulant heparan sulfate proteoglycans in the rat ovary peaks in preovulatory granulosa cells
GLYCOBIOLOGY
2001 vol. 11 pp. 183-194
PRINCIVALLE M, HASANS S, HOSSEINI G, DE AGOSTINI ARIANE

Characterization and hormonal modulation of anticoagulant heparan sulfate proteoglycans synthesized by rat ovarian granulosa cells
JOURNAL OF BIOLOGICAL CHEMISTRY
1996 vol. 271 pp. 22090-22099
HOSSEINI G, LIU J, DE AGOSTINI ARIANE

Differential parition of anticoagulant heparan sulfate proteoglycans synthesized by endothelial and fibroblastic cell lines
JOURNAL OF CELLULAR BIOCHEMISTRY
1994 vol. 54 pp. 174-185
DE AGOSTINI ARIANE, RAMUS MA, ROSENBERG RD

Research's domains




DATABASE-RESEARCH	GROUP OF CLINICAL BIOLOGY RESEARCH

Ariane DE AGOSTINI	Head of group CV	Research subject	Members of the group


	Links about the group Dr. Ariane DE AGOSTINI Fondation Recherches Médicales Avenue de la Roseraie, 64 1205 Genève Suisse Ariane.Deagostini@unige.ch Tel.: + 41 22 382 42 46 Fax: + 41 2 347 59 79 Comments Pages updated the 17.11.2015		Reseach's subject \| Group's publications \| Research's domains Anticoagulant heparan sulfates in female reproduction - New functions for anticoagulant heparan sulfates in female reproduction : study of the mechanism involved in ovulation and in placentation Major tissue remodeling occurs in hormone-responsive tissues of the female genital tract, at ovulation and during gestation, involving proteolysis and tightly controlled inflammation. Disorders of tissue remodeling events are associated with female infertility in women with ovarian dysfunction and with gestational pathologies as pre-eclampsia. Like heparin, anticoagulant heparan sulfate proteoglycans (aHSPG) bind and activate the coagulation inhibitor antithrombin III (AT). aHSPG are present in the vasculature and in the genital tract. The role of aHSPG in reproduction is demonstrated by the reduced fertility of mice harbouring an inactivated gene of 3-O-sulfotransferase, a key synthetic enzyme of aHSPG. These aHSPG deficient mice display multiple reproductive phenotypes, in the female ovulation is defective and gestation is hampered by inflammation around the placenta. Beyond their anticoagulant activity in the vascular bed, aHSPG seem to play novel and unsuspected functions in the reproductive system. Ovulation and placenta development during gestation require extensive tissue remodeling. aHSPG seem to be involved in the control of the limited inflammation associated to this remodeling and the aim or our current research is to establish the mechanism of aHSPG action and to determine which inflammation mediators are involved in this process (AT, cytokines). We use in vivo transgenic mice models as well as cell culture models (murine and human ovarian, uterine and trophoblastic cells). These models are manipulated by hormones and inflammation mediators to reveal the action mechanism of aHSPG. Recognition of the importance of aHSPG in reproductive physiology should allow to better understand the pathologies linked to the control of hemostasis and inflammation in the context of tissue remodeling during ovulation and gestation. Group's publications Removal of spermatozoa with externalized phosphatidylserine from sperm preparation in human assisted medical procreation: effects on viability, motility and mitochondrial membrane potential. REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY 2009 vol. 8 pp. 1-1 DE VANTERY ARRIGHI C, LUCAS H, CHARDONNENS D, DE AGOSTINI A Human follicular fluid heparan sulfate contains abundant 3-O-sulfated chains with anticoagulant activity. JOURNAL OF BIOLOGICAL CHEMISTRY 2008 vol. 283(42) pp. 28115-28124 DE AGOSTINI A AND AL An unexpected role for anticoagulant heparan sulfate proteoglycans in reproduction SWISS MEDICAL WEEKLY 2006 vol. 136(37-38) pp. 583-590 DE AGOSTINI ARIANE The majority of anticoagulant heparan sulfate is not absolutely essential for normal hemostasis JOURNAL OF CLINICAL INVESTIGATION 2003 vol. 111 pp. 989-999 HAJMOHAMMADI S., ENJOI K., PRINCIVALLE M., CHRISTI P., LECH M., BEELER D., RAYBURN H., SCHWARTZ J.J., BARZAGAR S., DE AGOSTINI ARIANE, POST M.J., ROSENBERG R.D., SHWORAK N.W. Coordinate expression of anticoagulant heparan sulfate proteoglycans and serine protease inhibitors in the rat ovary: a potent system of proteolysis control BIOLOGY OF REPRODUCTION 2002 vol. 66 pp. 144-158 HASAN S, HOSSEINI G, PRINCIVALLE M, DONG JC, BIRSAN D, CAGIDE C, DE AGOSTINI A Anticoagulant heparan sulfate proteoglycans in the rat ovary peaks in preovulatory granulosa cells GLYCOBIOLOGY 2001 vol. 11 pp. 183-194 PRINCIVALLE M, HASANS S, HOSSEINI G, DE AGOSTINI ARIANE Characterization and hormonal modulation of anticoagulant heparan sulfate proteoglycans synthesized by rat ovarian granulosa cells JOURNAL OF BIOLOGICAL CHEMISTRY 1996 vol. 271 pp. 22090-22099 HOSSEINI G, LIU J, DE AGOSTINI ARIANE Differential parition of anticoagulant heparan sulfate proteoglycans synthesized by endothelial and fibroblastic cell lines JOURNAL OF CELLULAR BIOCHEMISTRY 1994 vol. 54 pp. 174-185 DE AGOSTINI ARIANE, RAMUS MA, ROSENBERG RD Research's domains