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Published in: Reproductive Biology and Endocrinology 1/2021

Open Access 01-12-2021 | Infertility | Research

Expression of tissue factor and tissue factor pathway inhibitors during ovulation in rats: a relevance to the ovarian hyperstimulation syndrome

Authors: You Jee Jang, Hee Kyung Kim, Bum Chae Choi, Sang Jin Song, Jae Il Park, Sang Young Chun, Moon Kyoung Cho

Published in: Reproductive Biology and Endocrinology | Issue 1/2021

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Abstract

Background

Blood coagulation has been associated with ovulation and female infertility. In this study, the expression of the tissue factor system was examined during ovulation in immature rats; the correlation between tissue factor and ovarian hyperstimulation syndrome (OHSS) was evaluated both in rats and human follicular fluids.

Methods

Ovaries were obtained at various times after human chorionic gonadotropin (hCG) injection to investigate the expression of tissue factor system. Expression levels of ovarian tissue factor, tissue factor pathway inhibitor (Tfpi)-1 and Tfpi-2 genes and proteins were determined by real-time quantitative polymerase chain reaction (qPCR), and Western blot and immunofluorescence analyses, respectively. Expression levels of tissue factor system were also investigated in ovaries of OHSS-induced rats and in follicular fluid of infertile women.

Results

The expression of tissue factor in the preovulatory follicles was stimulated by hCG, reaching a maximum at 6 h. Tissue factor was expressed in the oocytes and the preovulatory follicles. Tfpi-2 mRNA levels were mainly increased by hCG in the granulosa cells whereas the mRNA levels of Tfpi-1 were decreased by hCG. Human CG-stimulated tissue factor expression was inhibited by the progesterone receptor antagonist. The increase in Tfpi-2 expression by hCG was decreased by the proliferator-activated receptor γ (PPARγ) antagonist. Decreased expression of the tissue factor was detected in OHSS-induced rats. Interestingly, the tissue factor concentrations in the follicular fluids of women undergoing in vitro fertilization were correlated with pregnancy but not with OHSS.

Conclusions

Collectively, the results indicate that tissue factor and Tfpi-2 expression is stimulated during the ovulatory process in rats; moreover, a correlation exists between the levels of tissue factor and OHSS in rats but not in humans.
Appendix
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Literature
1.
2.
go back to reference Oakley OR, Kim H, El-Amouri I, Lin PC, Cho J, Bani-Ahmad M, Ko C. Periovulatory leukocyte infiltration in the rat ovary. Endocrinology. 2010;151(9):4551–9.PubMedPubMedCentralCrossRef Oakley OR, Kim H, El-Amouri I, Lin PC, Cho J, Bani-Ahmad M, Ko C. Periovulatory leukocyte infiltration in the rat ovary. Endocrinology. 2010;151(9):4551–9.PubMedPubMedCentralCrossRef
3.
go back to reference Park JI, Jeon HJ, Jung NK, Jang YJ, Kim JS, Seo YW, Jeong M, Chae HZ, Chun SY. Periovulatory expression of hydrogen peroxide-induced sulfiredoxin and peroxiredoxin 2 in the rat ovary. Gonadotropin regulation and potential modification. Endocrinology. 2012;153(11):5512–21.PubMedCrossRef Park JI, Jeon HJ, Jung NK, Jang YJ, Kim JS, Seo YW, Jeong M, Chae HZ, Chun SY. Periovulatory expression of hydrogen peroxide-induced sulfiredoxin and peroxiredoxin 2 in the rat ovary. Gonadotropin regulation and potential modification. Endocrinology. 2012;153(11):5512–21.PubMedCrossRef
4.
go back to reference Parrott JA, Whaley PD, Skinner MK. Extrahepatic expression of fibrinogen by granulosa cells. Potential role in ovulation. Endocrinology. 1993;133(4):1645–9.PubMedCrossRef Parrott JA, Whaley PD, Skinner MK. Extrahepatic expression of fibrinogen by granulosa cells. Potential role in ovulation. Endocrinology. 1993;133(4):1645–9.PubMedCrossRef
5.
go back to reference Cheng Y, Kawamura K, Deguchi M, Takae S, Mulders SM, Hsueh AJ. Intraovarian thrombin and activated protein C signaling system regulates steroidogenesis during the periovulatory period. Mol Endocrinol. 2012;26(2):331–40.PubMedCrossRef Cheng Y, Kawamura K, Deguchi M, Takae S, Mulders SM, Hsueh AJ. Intraovarian thrombin and activated protein C signaling system regulates steroidogenesis during the periovulatory period. Mol Endocrinol. 2012;26(2):331–40.PubMedCrossRef
6.
go back to reference Roach LE, Petrik JJ, Plante L, LaMarre J, Gentry PA. Thrombin generation and presence of thrombin receptor in ovarian follicles. Biol Reprod. 2002;66(5):1350–8.PubMedCrossRef Roach LE, Petrik JJ, Plante L, LaMarre J, Gentry PA. Thrombin generation and presence of thrombin receptor in ovarian follicles. Biol Reprod. 2002;66(5):1350–8.PubMedCrossRef
7.
go back to reference Hirota Y, Tachibana O, Uchiyama N, Hayashi Y, Nakada M, Kita D, Watanabe T, Higashi R, Hamada J. Gonadotropin-releasing hormone (GnRH) and its receptor in human meningiomas. Clin Neurol Neurosurg. 2009;111(2):127–33.PubMedCrossRef Hirota Y, Tachibana O, Uchiyama N, Hayashi Y, Nakada M, Kita D, Watanabe T, Higashi R, Hamada J. Gonadotropin-releasing hormone (GnRH) and its receptor in human meningiomas. Clin Neurol Neurosurg. 2009;111(2):127–33.PubMedCrossRef
8.
go back to reference Gentry PA, Plante L, Schroeder MO, LaMarre J, Young JE, Dodds WG. Human ovarian follicular fluid has functional systems for the generation and modulation of thrombin. Fertil Steril. 2000;73(4):848–54.PubMedCrossRef Gentry PA, Plante L, Schroeder MO, LaMarre J, Young JE, Dodds WG. Human ovarian follicular fluid has functional systems for the generation and modulation of thrombin. Fertil Steril. 2000;73(4):848–54.PubMedCrossRef
9.
go back to reference Kim YS, Kim MS, Lee SH, Choi BC, Lim JM, Cha KY, Baek KH. Proteomic analysis of recurrent spontaneous abortion: identification of an inadequately expressed set of proteins in human follicular fluid. Proteomics. 2006;6(11):3445–54.PubMedCrossRef Kim YS, Kim MS, Lee SH, Choi BC, Lim JM, Cha KY, Baek KH. Proteomic analysis of recurrent spontaneous abortion: identification of an inadequately expressed set of proteins in human follicular fluid. Proteomics. 2006;6(11):3445–54.PubMedCrossRef
10.
go back to reference Cimmino G, Cirillo P. Tissue factor: newer concepts in thrombosis and its role beyond thrombosis and hemostasis. Cardiovasc Diagn Ther. 2018;8(5):581–93.PubMedPubMedCentralCrossRef Cimmino G, Cirillo P. Tissue factor: newer concepts in thrombosis and its role beyond thrombosis and hemostasis. Cardiovasc Diagn Ther. 2018;8(5):581–93.PubMedPubMedCentralCrossRef
11.
go back to reference Price GC, Thompson SA, Kam PC. Tissue factor and tissue factor pathway inhibitor. Anaesthesia. 2004;59(2004):483–92.PubMedCrossRef Price GC, Thompson SA, Kam PC. Tissue factor and tissue factor pathway inhibitor. Anaesthesia. 2004;59(2004):483–92.PubMedCrossRef
12.
go back to reference Bungay SD, Gentry PA, Gentry RD. Modelling thrombin generation in human ovarian follicular fluid. Bull Math Biol. 2006;68(8):2283–302.PubMedCrossRef Bungay SD, Gentry PA, Gentry RD. Modelling thrombin generation in human ovarian follicular fluid. Bull Math Biol. 2006;68(8):2283–302.PubMedCrossRef
13.
go back to reference Puttabyatappa M, Al-Alem LF, Zakerkish F, Rosewell KL, Brannstrom M, Curry TE Jr. Induction of tissue factor pathway inhibitor 2 by hCG regulates Periovulatory gene expression and plasmin activity. Endocrinology. 2017;158(1):109–20.PubMedCrossRef Puttabyatappa M, Al-Alem LF, Zakerkish F, Rosewell KL, Brannstrom M, Curry TE Jr. Induction of tissue factor pathway inhibitor 2 by hCG regulates Periovulatory gene expression and plasmin activity. Endocrinology. 2017;158(1):109–20.PubMedCrossRef
14.
go back to reference Kwak-Kim J, Yang KM, Gilman-Sachs A. Recurrent pregnancy loss: a disease of inflammation and coagulation. J Obstet Gynaecol Res. 2009;35(4):609–22.PubMedCrossRef Kwak-Kim J, Yang KM, Gilman-Sachs A. Recurrent pregnancy loss: a disease of inflammation and coagulation. J Obstet Gynaecol Res. 2009;35(4):609–22.PubMedCrossRef
15.
go back to reference Ebner T, Moser M, Shebl O, Sommergruber M, Yaman C, Tews G. Blood clots in the cumulus-oocyte complex predict poor oocyte quality and post-fertilization development. Reprod BioMed Online. 2008;16(6):801–7.PubMedCrossRef Ebner T, Moser M, Shebl O, Sommergruber M, Yaman C, Tews G. Blood clots in the cumulus-oocyte complex predict poor oocyte quality and post-fertilization development. Reprod BioMed Online. 2008;16(6):801–7.PubMedCrossRef
16.
17.
go back to reference Carvalho LML, Ferreira CN, Candido AL, Reis FM, Soter MO, Sales MF, Silva IFO, Nunes FFC, Gomes KB. Metformin reduces total microparticles and microparticles-expressing tissue factor in women with polycystic ovary syndrome. Arch Gynecol Obstet. 2017;296(4):617–21.PubMedCrossRef Carvalho LML, Ferreira CN, Candido AL, Reis FM, Soter MO, Sales MF, Silva IFO, Nunes FFC, Gomes KB. Metformin reduces total microparticles and microparticles-expressing tissue factor in women with polycystic ovary syndrome. Arch Gynecol Obstet. 2017;296(4):617–21.PubMedCrossRef
18.
go back to reference Gonzalez F, Kirwan JP, Rote NS, Minium J. Elevated circulating levels of tissue factor in polycystic ovary syndrome. Clin Appl Thromb Hemost. 2013;19(3):66–72.PubMedCrossRef Gonzalez F, Kirwan JP, Rote NS, Minium J. Elevated circulating levels of tissue factor in polycystic ovary syndrome. Clin Appl Thromb Hemost. 2013;19(3):66–72.PubMedCrossRef
19.
go back to reference Thyzel E, Siegling S, Tinneberg HR, Gotting C, Kleesiek K. Age dependent assessment of TFPI levels in follicular fluid of women undergoing IVF. Clin Chim Acta. 2005;361(1–2):176–81.PubMedCrossRef Thyzel E, Siegling S, Tinneberg HR, Gotting C, Kleesiek K. Age dependent assessment of TFPI levels in follicular fluid of women undergoing IVF. Clin Chim Acta. 2005;361(1–2):176–81.PubMedCrossRef
20.
go back to reference Delvigne A, Rozenberg S. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS). A review. Hum Reprod Update. 2002;8(6):559–77.PubMedCrossRef Delvigne A, Rozenberg S. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS). A review. Hum Reprod Update. 2002;8(6):559–77.PubMedCrossRef
21.
go back to reference Ishikawa K, Ohba T, Tanaka N, Iqbal M, Okamura Y, Okamura H. Organ-specific production control of vascular endothelial growth factor in ovarian hyperstimulation syndrome-model rats. Endocr J. 2003;50(5):515–25.PubMedCrossRef Ishikawa K, Ohba T, Tanaka N, Iqbal M, Okamura Y, Okamura H. Organ-specific production control of vascular endothelial growth factor in ovarian hyperstimulation syndrome-model rats. Endocr J. 2003;50(5):515–25.PubMedCrossRef
22.
go back to reference Ohba T, Ujioka T, Ishikawa K, Tanaka N, Okamura H. Ovarian hyperstimulation syndrome-model rats; the manifestation and clinical implication. Mol Cell Endocrinol. 2003;202(1–2):47–52.PubMedCrossRef Ohba T, Ujioka T, Ishikawa K, Tanaka N, Okamura H. Ovarian hyperstimulation syndrome-model rats; the manifestation and clinical implication. Mol Cell Endocrinol. 2003;202(1–2):47–52.PubMedCrossRef
23.
go back to reference Gao F, Vasquez SX, Su F, Roberts S, Shah N, Grijalva V, Imaizumi S, Chattopadhyay A, Ganapathy E, Meriwether D, Johnston B, Anantharamaiah GM, Navab M, Fogelman AM, Reddy ST, Farias-Eisner R. L-5F, an apolipoprotein A-I mimetic, inhibits tumor angiogenesis by suppressing VEGF/basic FGF signaling pathways. Integr Biol (Camb). 2011;3(4):479–89.CrossRef Gao F, Vasquez SX, Su F, Roberts S, Shah N, Grijalva V, Imaizumi S, Chattopadhyay A, Ganapathy E, Meriwether D, Johnston B, Anantharamaiah GM, Navab M, Fogelman AM, Reddy ST, Farias-Eisner R. L-5F, an apolipoprotein A-I mimetic, inhibits tumor angiogenesis by suppressing VEGF/basic FGF signaling pathways. Integr Biol (Camb). 2011;3(4):479–89.CrossRef
24.
go back to reference Shen BQ, Lee DY, Cortopassi KM, Damico LA, Zioncheck TF. Vascular endothelial growth factor KDR receptor signaling potentiates tumor necrosis factor-induced tissue factor expression in endothelial cells. J Biol Chem. 2001;276(7):5281–6.PubMedCrossRef Shen BQ, Lee DY, Cortopassi KM, Damico LA, Zioncheck TF. Vascular endothelial growth factor KDR receptor signaling potentiates tumor necrosis factor-induced tissue factor expression in endothelial cells. J Biol Chem. 2001;276(7):5281–6.PubMedCrossRef
25.
go back to reference Balasch J, Reverter JC, Fabregues F, Tassies D, Ordinas A, Vanrell JA. Increased induced monocyte tissue factor expression by plasma from patients with severe ovarian hyperstimulation syndrome. Fertil Steril. 1996;66(4):608–13.PubMedCrossRef Balasch J, Reverter JC, Fabregues F, Tassies D, Ordinas A, Vanrell JA. Increased induced monocyte tissue factor expression by plasma from patients with severe ovarian hyperstimulation syndrome. Fertil Steril. 1996;66(4):608–13.PubMedCrossRef
26.
go back to reference Rogolino A, Coccia ME, Fedi S, Gori AM, Cellai AP, Scarselli GF, Prisco D, Abbate R. Hypercoagulability, high tissue factor and low tissue factor pathway inhibitor levels in severe ovarian hyperstimulation syndrome: possible association with clinical outcome. Blood Coagul Fibrinolysis. 2003;14(3):277–82.PubMed Rogolino A, Coccia ME, Fedi S, Gori AM, Cellai AP, Scarselli GF, Prisco D, Abbate R. Hypercoagulability, high tissue factor and low tissue factor pathway inhibitor levels in severe ovarian hyperstimulation syndrome: possible association with clinical outcome. Blood Coagul Fibrinolysis. 2003;14(3):277–82.PubMed
27.
go back to reference Elchalal U, Schenker JG. The pathophysiology of ovarian hyperstimulation syndrome--views and ideas. Hum Reprod. 1997;12(6):1129–37.PubMedCrossRef Elchalal U, Schenker JG. The pathophysiology of ovarian hyperstimulation syndrome--views and ideas. Hum Reprod. 1997;12(6):1129–37.PubMedCrossRef
28.
go back to reference Robker RL, Hennebold JD, Russell DL. Coordination of ovulation and oocyte maturation: a good egg at the right time. Endocrinology. 2018;159(9):3209–18.PubMedPubMedCentralCrossRef Robker RL, Hennebold JD, Russell DL. Coordination of ovulation and oocyte maturation: a good egg at the right time. Endocrinology. 2018;159(9):3209–18.PubMedPubMedCentralCrossRef
29.
go back to reference Lydon JP, DeMayo FJ, Funk CR, Mani SK, Hughes AR, Montgomery CA Jr, Shyamala G, Conneely OM, O'Malley BW. Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities. Genes Dev. 1995;9(18):2266–78.PubMedCrossRef Lydon JP, DeMayo FJ, Funk CR, Mani SK, Hughes AR, Montgomery CA Jr, Shyamala G, Conneely OM, O'Malley BW. Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities. Genes Dev. 1995;9(18):2266–78.PubMedCrossRef
30.
go back to reference Parr EL. Absence of neutral proteinase activity in rat ovarian follicle walls at ovulation. Biol Reprod. 1974;11(5):509–12.PubMedCrossRef Parr EL. Absence of neutral proteinase activity in rat ovarian follicle walls at ovulation. Biol Reprod. 1974;11(5):509–12.PubMedCrossRef
31.
32.
go back to reference Lu E, Li C, Wang J, Zhang C. Inflammation and angiogenesis in the corpus luteum. J Obstet Gynaecol Res. 2019;45(10):1967–74.PubMedCrossRef Lu E, Li C, Wang J, Zhang C. Inflammation and angiogenesis in the corpus luteum. J Obstet Gynaecol Res. 2019;45(10):1967–74.PubMedCrossRef
33.
go back to reference Berisha B, Schams D, Rodler D, Pfaffl MW. Angiogenesis in the ovary - the Most important regulatory event for follicle and corpus luteum development and function in cow - an overview. Anat Histol Embryol. 2016;45(2):124–30.PubMedCrossRef Berisha B, Schams D, Rodler D, Pfaffl MW. Angiogenesis in the ovary - the Most important regulatory event for follicle and corpus luteum development and function in cow - an overview. Anat Histol Embryol. 2016;45(2):124–30.PubMedCrossRef
35.
go back to reference Zhang Y, Deng Y, Luther T, Müller M, Ziegler R, Waldherr R, Stern DM, Nawroth PP. Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice. J Clin Invest. 1994;94(3):1320–7.PubMedPubMedCentralCrossRef Zhang Y, Deng Y, Luther T, Müller M, Ziegler R, Waldherr R, Stern DM, Nawroth PP. Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice. J Clin Invest. 1994;94(3):1320–7.PubMedPubMedCentralCrossRef
36.
go back to reference Miura R, Haneda S, Matsui M. Ovulation of the preovulatory follicle originating from the first-wave dominant follicle leads to formation of an active corpus luteum. J Reprod Dev. 2015;61(4):317–23.PubMedPubMedCentralCrossRef Miura R, Haneda S, Matsui M. Ovulation of the preovulatory follicle originating from the first-wave dominant follicle leads to formation of an active corpus luteum. J Reprod Dev. 2015;61(4):317–23.PubMedPubMedCentralCrossRef
37.
go back to reference Kwik M, Maxwell E. Pathophysiology, treatment and prevention of ovarian hyperstimulation syndrome. Curr Opin Obstet Gynecol. 2016;28(4):236–41.PubMedCrossRef Kwik M, Maxwell E. Pathophysiology, treatment and prevention of ovarian hyperstimulation syndrome. Curr Opin Obstet Gynecol. 2016;28(4):236–41.PubMedCrossRef
38.
go back to reference Naredi N, Talwar P, Sandeep K. VEGF antagonist for the prevention of ovarian hyperstimulation syndrome: current status. Med J Armed Forces India. 2014;70(1):58–63.PubMedCrossRef Naredi N, Talwar P, Sandeep K. VEGF antagonist for the prevention of ovarian hyperstimulation syndrome: current status. Med J Armed Forces India. 2014;70(1):58–63.PubMedCrossRef
39.
go back to reference Shimada H, Kasakura S, Shiotani M, Nakamura K, Ikeuchi M, Hoshino T, Komatsu T, Ihara Y, Sohma M, Maeda Y, Matsuura R, Nakamura S, Hine C, Ohkura N, Kato H. Hypocoagulable state of human preovulatory ovarian follicular fluid: role of sulfated proteoglycan and tissue factor pathway inhibitor in the fluid. Biol Reprod. 2001;64(6):1739–45.PubMedCrossRef Shimada H, Kasakura S, Shiotani M, Nakamura K, Ikeuchi M, Hoshino T, Komatsu T, Ihara Y, Sohma M, Maeda Y, Matsuura R, Nakamura S, Hine C, Ohkura N, Kato H. Hypocoagulable state of human preovulatory ovarian follicular fluid: role of sulfated proteoglycan and tissue factor pathway inhibitor in the fluid. Biol Reprod. 2001;64(6):1739–45.PubMedCrossRef
40.
go back to reference Petersen LC, Sprecher CA, Foster DC, Blumberg H, Hamamoto T, Kisiel W. Inhibitory properties of a novel human Kunitz-type protease inhibitor homologous to tissue factor pathway inhibitor. Biochemistry. 1996;35(1):266–72.PubMedCrossRef Petersen LC, Sprecher CA, Foster DC, Blumberg H, Hamamoto T, Kisiel W. Inhibitory properties of a novel human Kunitz-type protease inhibitor homologous to tissue factor pathway inhibitor. Biochemistry. 1996;35(1):266–72.PubMedCrossRef
41.
go back to reference Iino M, Foster DC, Kisiel W. Quantification and characterization of human endothelial cell-derived tissue factor pathway inhibitor-2. Arterioscler Thromb Vasc Biol. 1998;18(1):40–6.PubMedCrossRef Iino M, Foster DC, Kisiel W. Quantification and characterization of human endothelial cell-derived tissue factor pathway inhibitor-2. Arterioscler Thromb Vasc Biol. 1998;18(1):40–6.PubMedCrossRef
42.
go back to reference Chand HS, Foster DC, Kisiel W. Structure, function and biology of tissue factor pathway inhibitor-2. Thromb Haemost. 2005;94(6):1122–30.PubMedCrossRef Chand HS, Foster DC, Kisiel W. Structure, function and biology of tissue factor pathway inhibitor-2. Thromb Haemost. 2005;94(6):1122–30.PubMedCrossRef
43.
go back to reference Rao CN, Cook B, Liu Y, Chilukuri K, Stack MS, Foster DC, Kisiel W, Woodley DT. HT-1080 fibrosarcoma cell matrix degradation and invasion are inhibited by the matrix-associated serine protease inhibitor TFPI-2/33 kDa MSPI. Int J Cancer. 1998;76(5):749–56.PubMedCrossRef Rao CN, Cook B, Liu Y, Chilukuri K, Stack MS, Foster DC, Kisiel W, Woodley DT. HT-1080 fibrosarcoma cell matrix degradation and invasion are inhibited by the matrix-associated serine protease inhibitor TFPI-2/33 kDa MSPI. Int J Cancer. 1998;76(5):749–56.PubMedCrossRef
44.
go back to reference Herman MP, Sukhova GK, Kisiel W, Foster D, Kehry MR, Libby P, Schonbeck U. Tissue factor pathway inhibitor-2 is a novel inhibitor of matrix metalloproteinases with implications for atherosclerosis. J Clin Invest. 2001;107(9):1117–26.PubMedPubMedCentralCrossRef Herman MP, Sukhova GK, Kisiel W, Foster D, Kehry MR, Libby P, Schonbeck U. Tissue factor pathway inhibitor-2 is a novel inhibitor of matrix metalloproteinases with implications for atherosclerosis. J Clin Invest. 2001;107(9):1117–26.PubMedPubMedCentralCrossRef
45.
go back to reference Komar CM. Peroxisome proliferator-activated receptors (PPARs) and ovarian function--implications for regulating steroidogenesis, differentiation, and tissue remodeling. Reprod Biol Endocrinol. 2005;3:41.PubMedPubMedCentralCrossRef Komar CM. Peroxisome proliferator-activated receptors (PPARs) and ovarian function--implications for regulating steroidogenesis, differentiation, and tissue remodeling. Reprod Biol Endocrinol. 2005;3:41.PubMedPubMedCentralCrossRef
Metadata
Title
Expression of tissue factor and tissue factor pathway inhibitors during ovulation in rats: a relevance to the ovarian hyperstimulation syndrome
Authors
You Jee Jang
Hee Kyung Kim
Bum Chae Choi
Sang Jin Song
Jae Il Park
Sang Young Chun
Moon Kyoung Cho
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2021
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-021-00708-1

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