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Published in: Journal of Ovarian Research 1/2012

Open Access 01-12-2012 | Research

Immunoreactivities of androgen receptor, estrogen receptors, p450arom, p450c17 proteins in wild ground squirrels ovaries during the nonbreeding and breeding seasons

Authors: Xiaonan Li, Haolin Zhang, Xia Sheng, Ben Li, Jiao Zhou, Meiyu Xu, Qiang Weng, Gen Watanabe, Kazuyoshi Taya

Published in: Journal of Ovarian Research | Issue 1/2012

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Abstract

The aim of this study was to elucidate the regulatory role of androgen in the follicular development of wild female ground squirrels. Immunohistochemical staining of FSHR, LHR, P450c17, P450arom, androgen receptor (AR), estrogen receptors (ERa and ERb) were executed in ovaries of female ground squirrels from both breeding and nonbreeding seasons. In addition, total ovarian proteins were extracted from the ovaries of squirrels from breeding and nonbreeding seasons, and Western blot analysis were performed in order to probe for FSHR, LHR, P450c17, P450arom, AR, ERa and ERb. The results of immunohistochemical staining and Western blotting of P450c17 showed that there was no significant difference between the breeding and nonbreeding seasons. It was found that granulosa cells expressed P450arom during the breeding season. In contrast, there was no positive staining of P450arom in the nonbreeding season. There was no significant difference in immunoreactivity of AR between the breeding and nonbreeding seasons. However, the immunoreactivities of ERa and ERb were both significantly reduced in the nonbreeding season compared to the breeding season. The positive stains of FSHR and LHR were found in the granulosa cells and theca cells of the ovaries of the breeding and nonbreeding seasons. In addition, the Western blotting results of FSHR and LHR showed a significant reduction in the nonbreeding season compared with the breeding season. These findings suggested that androgen might be predominantly converted into estrogen in order to regulate the follicular development via binding of estrogen receptors during the breeding season, whereas androgen might predominantly directly bind androgen receptor to regulate the follicular development during the nonbreeding season in the ovaries of wild female ground squirrels.
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Literature
2.
go back to reference Tan O, Fadiel A, Chang A, Demir N, Jeffrey R, Horvath T, Garcia-Segura LM, Naftolin F: Estrogens regulate posttranslational modification of neural cell adhesion molecule during the estrogen-induced gonadotropin surge. Endocrinology 2009, 150: 2783–2790. 10.1210/en.2008-0927PubMedCrossRef Tan O, Fadiel A, Chang A, Demir N, Jeffrey R, Horvath T, Garcia-Segura LM, Naftolin F: Estrogens regulate posttranslational modification of neural cell adhesion molecule during the estrogen-induced gonadotropin surge. Endocrinology 2009, 150: 2783–2790. 10.1210/en.2008-0927PubMedCrossRef
3.
go back to reference Couse JF, Yates MM, Walker VR, Korach KS: Characterization of the hypothalamic-pituitary-gonadal axis in estrogen receptor (ER) Null mice reveals hypergonadism and endocrine sex reversal in females lacking ERalpha but not ERbeta. Mol Endocrinol 2003, 17: 1039–1053. 10.1210/me.2002-0398PubMedCrossRef Couse JF, Yates MM, Walker VR, Korach KS: Characterization of the hypothalamic-pituitary-gonadal axis in estrogen receptor (ER) Null mice reveals hypergonadism and endocrine sex reversal in females lacking ERalpha but not ERbeta. Mol Endocrinol 2003, 17: 1039–1053. 10.1210/me.2002-0398PubMedCrossRef
4.
go back to reference Payne AH, Hales DB: Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocr Rev 2004, 25: 947–970. 10.1210/er.2003-0030PubMedCrossRef Payne AH, Hales DB: Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocr Rev 2004, 25: 947–970. 10.1210/er.2003-0030PubMedCrossRef
5.
go back to reference Irusta G, Parborell F, Tesone M: Inhibition of cytochrome P-450 C17 enzyme by a GnRH agonist in ovarian follicles from gonadotropin-stimulated rats. Am J Physiol Endocrinol Metab 2007, 292: 1456–1464. 10.1152/ajpendo.00226.2006CrossRef Irusta G, Parborell F, Tesone M: Inhibition of cytochrome P-450 C17 enzyme by a GnRH agonist in ovarian follicles from gonadotropin-stimulated rats. Am J Physiol Endocrinol Metab 2007, 292: 1456–1464. 10.1152/ajpendo.00226.2006CrossRef
6.
go back to reference Irving-Rodgers HF, Krupa M, Rodgers RJ: Cholesterol side-chain cleavage cytochrome P450 and 3beta-hydroxysteroid dehydrogenase expression and the concentrations of steroid hormones in the follicular fluids of different phenotypes of healthy and atretic bovine ovarian follicles. Biol Reprod 2003, 69: 2022–2028. 10.1095/biolreprod.103.017442PubMedCrossRef Irving-Rodgers HF, Krupa M, Rodgers RJ: Cholesterol side-chain cleavage cytochrome P450 and 3beta-hydroxysteroid dehydrogenase expression and the concentrations of steroid hormones in the follicular fluids of different phenotypes of healthy and atretic bovine ovarian follicles. Biol Reprod 2003, 69: 2022–2028. 10.1095/biolreprod.103.017442PubMedCrossRef
7.
go back to reference Vanselow J, Fürbass R, Rehbock F, Klautschek G, Schwerin M: Cattle and sheep use different promoters to direct the expression of the aromatase cytochrome P450 encoding gene, Cyp19, during pregnancy. Domest Anim Endocrinol 2004, 27: 99–114. 10.1016/j.domaniend.2004.01.008PubMedCrossRef Vanselow J, Fürbass R, Rehbock F, Klautschek G, Schwerin M: Cattle and sheep use different promoters to direct the expression of the aromatase cytochrome P450 encoding gene, Cyp19, during pregnancy. Domest Anim Endocrinol 2004, 27: 99–114. 10.1016/j.domaniend.2004.01.008PubMedCrossRef
8.
go back to reference Brooke AM, Taylor NF, Shepherd JH, Gore ME, Ahmad T, Lin L, Rumsby G, Papari-Zareei M, Auchus RJ, Achermann JC, Monson JP: A novel point mutation in P450c17 (CYP17) causing combined 17alpha-hydroxylase/17, 20-lyase deficiency. J Clin Endocrinol Metab 2006, 91: 2428–2431. 10.1210/jc.2005-2653PubMedCrossRef Brooke AM, Taylor NF, Shepherd JH, Gore ME, Ahmad T, Lin L, Rumsby G, Papari-Zareei M, Auchus RJ, Achermann JC, Monson JP: A novel point mutation in P450c17 (CYP17) causing combined 17alpha-hydroxylase/17, 20-lyase deficiency. J Clin Endocrinol Metab 2006, 91: 2428–2431. 10.1210/jc.2005-2653PubMedCrossRef
9.
go back to reference Yuan JH, Wang JZ, Lan GC, Sui HS, Yu JN, Tan JH: Expression of steroidogenic enzymes and synthesis of steroid hormones during development of ovarian follicles in prepubertal goats. Domest Anim Endocrinol 2008, 34: 451–460. 10.1016/j.domaniend.2008.01.002PubMedCrossRef Yuan JH, Wang JZ, Lan GC, Sui HS, Yu JN, Tan JH: Expression of steroidogenic enzymes and synthesis of steroid hormones during development of ovarian follicles in prepubertal goats. Domest Anim Endocrinol 2008, 34: 451–460. 10.1016/j.domaniend.2008.01.002PubMedCrossRef
10.
go back to reference Weng Q, Medan MS, Ren L, Watanabe G, Tsubota T, Taya K: Immunolocalization of steroidogenic enzymes in the corpus luteum and placenta of the Japanese Shiba goat. J Reprod Dev 2005, 51: 247–252. 10.1262/jrd.16081PubMedCrossRef Weng Q, Medan MS, Ren L, Watanabe G, Tsubota T, Taya K: Immunolocalization of steroidogenic enzymes in the corpus luteum and placenta of the Japanese Shiba goat. J Reprod Dev 2005, 51: 247–252. 10.1262/jrd.16081PubMedCrossRef
11.
go back to reference Kananen K, Markkula M, Rainio E, Su JG, Hsueh AJ, Huhtaniemi IT: Gonadal tumorigenesis in transgenic mice bearing the mouse inhibin alpha-subunit promoter/simian virus T-antigen fusion gene: characterization of ovarian tumors and establishment of gonadotropin-responsive granulosa cell lines. Mol Endocrinol 1995, 9: 616–627. 10.1210/me.9.5.616PubMed Kananen K, Markkula M, Rainio E, Su JG, Hsueh AJ, Huhtaniemi IT: Gonadal tumorigenesis in transgenic mice bearing the mouse inhibin alpha-subunit promoter/simian virus T-antigen fusion gene: characterization of ovarian tumors and establishment of gonadotropin-responsive granulosa cell lines. Mol Endocrinol 1995, 9: 616–627. 10.1210/me.9.5.616PubMed
12.
go back to reference Gore-Langton RE, Armstrong DT: Follicular steroidogenesis and its control. In The Physiology of Reproduction. Edited by: Knobil E, Neill JD. Raven Press, New York; 1988:331–385. Gore-Langton RE, Armstrong DT: Follicular steroidogenesis and its control. In The Physiology of Reproduction. Edited by: Knobil E, Neill JD. Raven Press, New York; 1988:331–385.
13.
go back to reference Emmen JM, Couse JF, Elmore SA, Yates MM, Kissling GE, Korach KS: In vitro growth and ovulation of follicles from ovaries of estrogen receptor (ER){alpha} and ER{beta} null mice indicate a role for ER{beta} in follicular maturation. Endocrinology 2005, 146: 2817–2826. 10.1210/en.2004-1108PubMedCrossRef Emmen JM, Couse JF, Elmore SA, Yates MM, Kissling GE, Korach KS: In vitro growth and ovulation of follicles from ovaries of estrogen receptor (ER){alpha} and ER{beta} null mice indicate a role for ER{beta} in follicular maturation. Endocrinology 2005, 146: 2817–2826. 10.1210/en.2004-1108PubMedCrossRef
14.
go back to reference Lubahn DB, Joseph DR, Sullivan PM, Willard HF, French FS, Wilson EM: Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science 1988, 240: 327–330. 10.1126/science.3353727PubMedCrossRef Lubahn DB, Joseph DR, Sullivan PM, Willard HF, French FS, Wilson EM: Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science 1988, 240: 327–330. 10.1126/science.3353727PubMedCrossRef
15.
go back to reference Walters KA, Allan CM, Handelsman DJ: Androgen actions and the ovary. Biol Reprod 2008, 78: 380–389. 10.1095/biolreprod.107.064089PubMedCrossRef Walters KA, Allan CM, Handelsman DJ: Androgen actions and the ovary. Biol Reprod 2008, 78: 380–389. 10.1095/biolreprod.107.064089PubMedCrossRef
16.
go back to reference Shiina H, Matsumoto T, Sato T, Igarashi K, Miyamoto J, Takemasa S, Sakari M, Takada I, Nakamura T, Metzger D, Chambon P, Kanno J, Yoshikawa H, Kato S: Premature ovarian failure in androgen receptor-deficient mice. Proc Natl Acad Sci U S A 2006, 103: 224–229. 10.1073/pnas.0506736102PubMedCentralPubMedCrossRef Shiina H, Matsumoto T, Sato T, Igarashi K, Miyamoto J, Takemasa S, Sakari M, Takada I, Nakamura T, Metzger D, Chambon P, Kanno J, Yoshikawa H, Kato S: Premature ovarian failure in androgen receptor-deficient mice. Proc Natl Acad Sci U S A 2006, 103: 224–229. 10.1073/pnas.0506736102PubMedCentralPubMedCrossRef
17.
go back to reference Tetsuka M, Whitelaw PF, Bremner WJ, Millar MR, Smyth CD, Hillier SG: Developmental regulation of androgen receptor in rat ovary. J Endocrinol 1995, 145: 535–543. 10.1677/joe.0.1450535PubMedCrossRef Tetsuka M, Whitelaw PF, Bremner WJ, Millar MR, Smyth CD, Hillier SG: Developmental regulation of androgen receptor in rat ovary. J Endocrinol 1995, 145: 535–543. 10.1677/joe.0.1450535PubMedCrossRef
18.
go back to reference Sheng X, Zhang H, Zhang M, Zhang W, Hu X, Song M, Zhou J, Xu M, Weng Q, Watanabe G, Taya K: Seasonal changes in immunoreactivity of activin signaling component proteins in wild ground squirrels testes. J Reprod Dev 2012, 58: 126–131. 10.1262/jrd.11-005SPubMedCrossRef Sheng X, Zhang H, Zhang M, Zhang W, Hu X, Song M, Zhou J, Xu M, Weng Q, Watanabe G, Taya K: Seasonal changes in immunoreactivity of activin signaling component proteins in wild ground squirrels testes. J Reprod Dev 2012, 58: 126–131. 10.1262/jrd.11-005SPubMedCrossRef
19.
go back to reference Sheng X, Zhang H, Zhang W, Song M, Zhang M, Li B, Weng Q, Watanabe G, Taya K: Seasonal changes in spermatogenesis and immunolocalization of inhibin/activin subunits in the wild male ground squirrels (Citellus dauricus Brandt). J Reprod Dev 2008, 54: 460–464. 10.1262/jrd.20032PubMedCrossRef Sheng X, Zhang H, Zhang W, Song M, Zhang M, Li B, Weng Q, Watanabe G, Taya K: Seasonal changes in spermatogenesis and immunolocalization of inhibin/activin subunits in the wild male ground squirrels (Citellus dauricus Brandt). J Reprod Dev 2008, 54: 460–464. 10.1262/jrd.20032PubMedCrossRef
20.
go back to reference Zhang H, Sheng X, Hu X, Li X, Xu H, Zhang M, Li B, Xu M, Weng Q, Zhang Z, Taya K: Seasonal changes in spermatogenesis and immunolocalization of cytochrome P450 17alpha-hydroxylase/c17–20 lyase and cytochrome P450 aromatase in the wild male ground squirrels (Citellus dauricus Brandt). J Reprod Dev 2010, 56: 297–302. 10.1262/jrd.09-078TPubMedCrossRef Zhang H, Sheng X, Hu X, Li X, Xu H, Zhang M, Li B, Xu M, Weng Q, Zhang Z, Taya K: Seasonal changes in spermatogenesis and immunolocalization of cytochrome P450 17alpha-hydroxylase/c17–20 lyase and cytochrome P450 aromatase in the wild male ground squirrels (Citellus dauricus Brandt). J Reprod Dev 2010, 56: 297–302. 10.1262/jrd.09-078TPubMedCrossRef
21.
go back to reference Sheng X, Weng J, Zhang H, Li X, Zhang M, Xu M, Weng Q, Watanabe G, Taya K: Immunohistochemical localization of inhibin/activin subunits in the wild ground squirrel (Citellus dauricus Brandt) ovary. J Reprod Dev 2012., 58: in press Sheng X, Weng J, Zhang H, Li X, Zhang M, Xu M, Weng Q, Watanabe G, Taya K: Immunohistochemical localization of inhibin/activin subunits in the wild ground squirrel (Citellus dauricus Brandt) ovary. J Reprod Dev 2012., 58: in press
22.
go back to reference Hales DB, Sha LL, Payne AH: Testosterone inhibits cAMP-induced de Novo synthesis of Leydig cell cytochrome P-450(17 alpha) by an androgen receptor-mediated mechanism. J Biol Chem 1987, 262: 11200–11206.PubMed Hales DB, Sha LL, Payne AH: Testosterone inhibits cAMP-induced de Novo synthesis of Leydig cell cytochrome P-450(17 alpha) by an androgen receptor-mediated mechanism. J Biol Chem 1987, 262: 11200–11206.PubMed
23.
go back to reference Kitawaki J, Yoshida N, Osawa Y: An enzyme-linked immunosorbent assay for quantitation of aromatase cytochrome P-450. Endocrinology 1989, 124: 1417–1423. 10.1210/endo-124-3-1417PubMedCrossRef Kitawaki J, Yoshida N, Osawa Y: An enzyme-linked immunosorbent assay for quantitation of aromatase cytochrome P-450. Endocrinology 1989, 124: 1417–1423. 10.1210/endo-124-3-1417PubMedCrossRef
24.
go back to reference Bertoldo M, Holyoake PK, Evans G, Grupen CG: Oocyte developmental competence is reduced in sows during the seasonal infertility period. Reprod Fertil Dev 2010, 22: 1222–1229. 10.1071/RD10093PubMedCrossRef Bertoldo M, Holyoake PK, Evans G, Grupen CG: Oocyte developmental competence is reduced in sows during the seasonal infertility period. Reprod Fertil Dev 2010, 22: 1222–1229. 10.1071/RD10093PubMedCrossRef
25.
go back to reference Singh J, Nanda AS, Adams GP: The reproductive pattern and efficiency of female buffaloes. Anim Reprod Sci 2000, 60–61: 593–604.PubMedCrossRef Singh J, Nanda AS, Adams GP: The reproductive pattern and efficiency of female buffaloes. Anim Reprod Sci 2000, 60–61: 593–604.PubMedCrossRef
26.
go back to reference Bao B, Garverick HA: Expression of steroidogenic enzyme and gonadotropin receptor genes in bovine follicles during ovarian follicular waves: a review. J Anim Sci 1998, 76: 903–1921. Bao B, Garverick HA: Expression of steroidogenic enzyme and gonadotropin receptor genes in bovine follicles during ovarian follicular waves: a review. J Anim Sci 1998, 76: 903–1921.
27.
go back to reference Bao B, Garverick HA, Smith GW, Smith MF, Salfen BE, Youngquist RS: Changes in messenger ribonucleic acid encoding luteinizing hormone receptor, cytochrome P450-side chain cleavage, and aromatase are associated with recruitment and selection of bovine ovarian follicles. Biol Reprod 1997, 56: 1158–1168. 10.1095/biolreprod56.5.1158PubMedCrossRef Bao B, Garverick HA, Smith GW, Smith MF, Salfen BE, Youngquist RS: Changes in messenger ribonucleic acid encoding luteinizing hormone receptor, cytochrome P450-side chain cleavage, and aromatase are associated with recruitment and selection of bovine ovarian follicles. Biol Reprod 1997, 56: 1158–1168. 10.1095/biolreprod56.5.1158PubMedCrossRef
28.
go back to reference Xu Z, Garverick HA, Smith GW, Smith MF, Hamilton SA, Youngquist RS: Expression of follicle-stimulating hormone and luteinizing hormone receptor messenger ribonucleic acids in bovine follicles during the first follicular wave. Biol Reprod 1995, 53: 951–957. 10.1095/biolreprod53.4.951PubMedCrossRef Xu Z, Garverick HA, Smith GW, Smith MF, Hamilton SA, Youngquist RS: Expression of follicle-stimulating hormone and luteinizing hormone receptor messenger ribonucleic acids in bovine follicles during the first follicular wave. Biol Reprod 1995, 53: 951–957. 10.1095/biolreprod53.4.951PubMedCrossRef
29.
go back to reference Hsueh AJ, Adashi EY, Jones PB, Welsh TH Jr: Hormonal regulation of the differentiation of cultured ovarian granulosa cells. Endocr Rev 1984, 5: 76–127. 10.1210/edrv-5-1-76PubMedCrossRef Hsueh AJ, Adashi EY, Jones PB, Welsh TH Jr: Hormonal regulation of the differentiation of cultured ovarian granulosa cells. Endocr Rev 1984, 5: 76–127. 10.1210/edrv-5-1-76PubMedCrossRef
31.
32.
go back to reference Araki H, Tsubota T, Maeda N, Harada N, Kominami S, Mason JI, Kita I: Intraovarian immunolocalization of steroidogenic enzymes in a Hokkaido brown bear, Ursus arctos yesoensis during the mating season. J Vet Med Sci 1996, 58: 787–790. 10.1292/jvms.58.787PubMedCrossRef Araki H, Tsubota T, Maeda N, Harada N, Kominami S, Mason JI, Kita I: Intraovarian immunolocalization of steroidogenic enzymes in a Hokkaido brown bear, Ursus arctos yesoensis during the mating season. J Vet Med Sci 1996, 58: 787–790. 10.1292/jvms.58.787PubMedCrossRef
33.
go back to reference Takayama K, Fukaya T, Sasano H, Funayama Y, Suzuki T, Takaya R, Wada Y, Yajima A: Immunohistochemical study of steroidogenesis and cell proliferation in polycystic ovarian syndrome. Hum Reprod 1996, 11: 1387–1392. 10.1093/oxfordjournals.humrep.a019405PubMedCrossRef Takayama K, Fukaya T, Sasano H, Funayama Y, Suzuki T, Takaya R, Wada Y, Yajima A: Immunohistochemical study of steroidogenesis and cell proliferation in polycystic ovarian syndrome. Hum Reprod 1996, 11: 1387–1392. 10.1093/oxfordjournals.humrep.a019405PubMedCrossRef
34.
go back to reference Cheng G, Weihua Z, Mäkinen S, Mäkelä S, Saji S, Warner M, Gustafsson JA, Hovatta O: A role for the androgen receptor in follicular atresia of estrogen receptor beta knockout mouse ovary. Biol Reprod 2002, 66: 77–84. 10.1095/biolreprod66.1.77PubMedCrossRef Cheng G, Weihua Z, Mäkinen S, Mäkelä S, Saji S, Warner M, Gustafsson JA, Hovatta O: A role for the androgen receptor in follicular atresia of estrogen receptor beta knockout mouse ovary. Biol Reprod 2002, 66: 77–84. 10.1095/biolreprod66.1.77PubMedCrossRef
35.
go back to reference Vendola KA, Zhou J, Adesanya OO, Weil SJ, Bondy CA: Androgen stimulate early stages of follicular growth in the primate ovary. J Clin Invest 1998, 101: 2622–2629. 10.1172/JCI2081PubMedCentralPubMedCrossRef Vendola KA, Zhou J, Adesanya OO, Weil SJ, Bondy CA: Androgen stimulate early stages of follicular growth in the primate ovary. J Clin Invest 1998, 101: 2622–2629. 10.1172/JCI2081PubMedCentralPubMedCrossRef
36.
go back to reference Leung PC, Armstrong DT: Interactions of steroids and gonadotropins in the control of steroidogenesis in the ovarian follicle. Annu Rev Physiol 1980, 42: 71–82. 10.1146/annurev.ph.42.030180.000443PubMedCrossRef Leung PC, Armstrong DT: Interactions of steroids and gonadotropins in the control of steroidogenesis in the ovarian follicle. Annu Rev Physiol 1980, 42: 71–82. 10.1146/annurev.ph.42.030180.000443PubMedCrossRef
37.
go back to reference McNatty KP, Smith DM, Makris A, Osathanondh R, Ryan KJ: The microenvironment of the human antral follicle: interrelationships among the steroid levels in antral fluid, the population of granulosa cells, and the status of the oocyte in vivo and in vitro. J Clin Endocrinol Metab 1979, 49: 851–860. 10.1210/jcem-49-6-851PubMedCrossRef McNatty KP, Smith DM, Makris A, Osathanondh R, Ryan KJ: The microenvironment of the human antral follicle: interrelationships among the steroid levels in antral fluid, the population of granulosa cells, and the status of the oocyte in vivo and in vitro. J Clin Endocrinol Metab 1979, 49: 851–860. 10.1210/jcem-49-6-851PubMedCrossRef
38.
go back to reference Westergaard L, Christensen IJ, McNatty KP: Steroid levels in ovarian follicular fluid related to follicle size and health status during the normal menstrual cycle in women. Hum Reprod 1986, 1: 227–232.PubMed Westergaard L, Christensen IJ, McNatty KP: Steroid levels in ovarian follicular fluid related to follicle size and health status during the normal menstrual cycle in women. Hum Reprod 1986, 1: 227–232.PubMed
Metadata
Title
Immunoreactivities of androgen receptor, estrogen receptors, p450arom, p450c17 proteins in wild ground squirrels ovaries during the nonbreeding and breeding seasons
Authors
Xiaonan Li
Haolin Zhang
Xia Sheng
Ben Li
Jiao Zhou
Meiyu Xu
Qiang Weng
Gen Watanabe
Kazuyoshi Taya
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2012
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/1757-2215-5-26

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