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Published in: Reproductive Biology and Endocrinology 1/2010

Open Access 01-12-2010 | Research

Remarkable features of ovarian morphology and reproductive hormones in insulin-resistant Zucker fatty (fa/fa) rats

Authors: Hiroyuki Honnma, Toshiaki Endo, Tamotsu Kiya, Ayumi Shimizu, Kunihiko Nagasawa, Tsuyoshi Baba, Takashi Fujimoto, Hirofumi Henmi, Yoshimitsu Kitajima, Kengo Manase, Shinichi Ishioka, Eiki Ito, Tsuyoshi Saito

Published in: Reproductive Biology and Endocrinology | Issue 1/2010

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Abstract

Background

Zucker fatty (fa/fa) rats are a well-understood model of obesity and hyperinsulinemia. It is now thought that obesity/hyperinsulinemia is an important cause of endocrinological abnormality, but to date there have been no reports on the changes in ovarian morphology or the ovarian androgen profile in rat models of obesity and insulin resistance.

Methods

In this study we investigated the effects of obesity and hyperinsulinemia on ovarian morphology and the hormone profile in insulin-resistant Zucker fatty rats (5, 8, 12 and 16 weeks of age, n = 6-7).

Results

Ovaries from 5-week-old fatty rats had significantly greater total and atretic follicle numbers, and higher atretic-to-total follicle ratios than those from lean rats. Ovaries from 12- and 16-week-old fatty rats showed interstitial cell hyperplasia and numerous cysts with features of advanced follicular atresia. In addition, serum testosterone and androstenedione levels significantly declined in fatty rats from age 8 to 16 weeks, so that fatty rats showed significantly lower levels of serum testosterone (12 and 16 weeks) and androstenedione (all weeks) than lean rats. This may reflect a reduction of androgen synthesis during follicular atresia. Serum adiponectin levels were high in immature fatty rats, and although the levels declined significantly as they matured, it remained significantly higher in fatty rats than in lean rats. On the other hand, levels of ovarian adiponectin and its receptors were significantly lower in mature fatty rats than in lean mature rats or immature fatty rats.

Conclusions

Our findings indicate that ovarian morphology and hormone profiles are significantly altered by the continuous insulin resistance in Zucker fatty rats. Simultaneously, abrupt reductions in serum and ovarian adiponectin also likely contribute to the infertility seen in fatty rats.
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Literature
1.
go back to reference Penicaud L, Ferre P, Terretaz J, Kinebanyan MF, Leturque A, Dore E, Girard J, Jeanrenaud B, Picon L: Development of obesity in Zucker rats. Early insulin resistance in muscles but normal sensitivity in white adipose tissue. Diabetes. 1987, 36: 626-631. 10.2337/diabetes.36.5.626.CrossRefPubMed Penicaud L, Ferre P, Terretaz J, Kinebanyan MF, Leturque A, Dore E, Girard J, Jeanrenaud B, Picon L: Development of obesity in Zucker rats. Early insulin resistance in muscles but normal sensitivity in white adipose tissue. Diabetes. 1987, 36: 626-631. 10.2337/diabetes.36.5.626.CrossRefPubMed
2.
go back to reference Bray GA: The Zucker-fatty rat: a review. Fed Proc. 1977, 36: 148-153.PubMed Bray GA: The Zucker-fatty rat: a review. Fed Proc. 1977, 36: 148-153.PubMed
3.
go back to reference Zucker LM, Antoniades HN: Insulin and obesity in the Zucker genetically obese "fatty" rat. Endocrinology. 1972, 90: 1320-1330. 10.1210/endo-90-5-1320.CrossRefPubMed Zucker LM, Antoniades HN: Insulin and obesity in the Zucker genetically obese "fatty" rat. Endocrinology. 1972, 90: 1320-1330. 10.1210/endo-90-5-1320.CrossRefPubMed
4.
go back to reference Stern J, Johnson PR, Greenwood MR, Zucker LM, Hirsch J: Insulin resistance and pancreatic insulin release in the genetically obese Zucker rat. Proc Soc Exp Biol Med. 1972, 139: 66-69.CrossRefPubMed Stern J, Johnson PR, Greenwood MR, Zucker LM, Hirsch J: Insulin resistance and pancreatic insulin release in the genetically obese Zucker rat. Proc Soc Exp Biol Med. 1972, 139: 66-69.CrossRefPubMed
5.
go back to reference Marin Bivens CL, Olster DH: Abnormal estrous cyclicity and behavioral hyporesponsiveness to ovarian hormones in genetically obese Zucker female rats. Endocrinology. 1997, 138: 143-148. 10.1210/en.138.1.143.PubMed Marin Bivens CL, Olster DH: Abnormal estrous cyclicity and behavioral hyporesponsiveness to ovarian hormones in genetically obese Zucker female rats. Endocrinology. 1997, 138: 143-148. 10.1210/en.138.1.143.PubMed
6.
go back to reference Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y: Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol. 2000, 20: 1595-1599.CrossRefPubMed Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y: Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol. 2000, 20: 1595-1599.CrossRefPubMed
7.
go back to reference Stefan N, Stumvoll M: Adiponectin--its role in metabolism and beyond. Horm Metab Res. 2002, 34: 469-474. 10.1055/s-2002-34785.CrossRefPubMed Stefan N, Stumvoll M: Adiponectin--its role in metabolism and beyond. Horm Metab Res. 2002, 34: 469-474. 10.1055/s-2002-34785.CrossRefPubMed
8.
go back to reference Matsubara M, Maruoka S, Katayose S: Decreased plasma adiponectin concentrations in women with dyslipidemia. J Clin Endocrinol Metab. 2002, 87: 2764-2769. 10.1210/jc.87.6.2764.CrossRefPubMed Matsubara M, Maruoka S, Katayose S: Decreased plasma adiponectin concentrations in women with dyslipidemia. J Clin Endocrinol Metab. 2002, 87: 2764-2769. 10.1210/jc.87.6.2764.CrossRefPubMed
9.
go back to reference Kazumi T, Kawaguchi A, Sakai K, Hirano T, Yoshino G: Young men with high-normal blood pressure have lower serum adiponectin, smaller LDL size, and higher elevated heart rate than those with optimal blood pressure. Diabetes Care. 2002, 25: 971-976. 10.2337/diacare.25.6.971.CrossRefPubMed Kazumi T, Kawaguchi A, Sakai K, Hirano T, Yoshino G: Young men with high-normal blood pressure have lower serum adiponectin, smaller LDL size, and higher elevated heart rate than those with optimal blood pressure. Diabetes Care. 2002, 25: 971-976. 10.2337/diacare.25.6.971.CrossRefPubMed
10.
go back to reference Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y: Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999, 257: 79-83. 10.1006/bbrc.1999.0255.CrossRefPubMed Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y: Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999, 257: 79-83. 10.1006/bbrc.1999.0255.CrossRefPubMed
11.
go back to reference Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA: Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001, 86: 1930-1935. 10.1210/jc.86.5.1930.CrossRefPubMed Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA: Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001, 86: 1930-1935. 10.1210/jc.86.5.1930.CrossRefPubMed
12.
go back to reference Lin LY, Lin CY, Su TC, Liau CS: Angiotensin II-induced apoptosis in human endothelial cells is inhibited by adiponectin through restoration of the association between endothelial nitric oxide synthase and heat shock protein 90. FEBS Lett. 2004, 574: 106-110. 10.1016/j.febslet.2004.08.012.CrossRefPubMed Lin LY, Lin CY, Su TC, Liau CS: Angiotensin II-induced apoptosis in human endothelial cells is inhibited by adiponectin through restoration of the association between endothelial nitric oxide synthase and heat shock protein 90. FEBS Lett. 2004, 574: 106-110. 10.1016/j.febslet.2004.08.012.CrossRefPubMed
13.
go back to reference Oana F, Takeda H, Hayakawa K, Matsuzawa A, Akahane S, Isaji M, Akahane M: Physiological difference between obese (fa/fa) Zucker rats and lean Zucker rats concerning adiponectin. Metabolism. 2005, 54: 995-1001. 10.1016/j.metabol.2005.02.016.CrossRefPubMed Oana F, Takeda H, Hayakawa K, Matsuzawa A, Akahane S, Isaji M, Akahane M: Physiological difference between obese (fa/fa) Zucker rats and lean Zucker rats concerning adiponectin. Metabolism. 2005, 54: 995-1001. 10.1016/j.metabol.2005.02.016.CrossRefPubMed
14.
go back to reference Caminos JE, Nogueiras R, Gaytan F, Pineda R, Gonzalez CR, Barreiro ML, Castano JP, Malagon MM, Pinilla L, Toppari J, Diéguez C, Tena-Sempere M: Novel expression and direct effects of adiponectin in the rat testis. Endocrinology. 2008, 149: 3390-3402. 10.1210/en.2007-1582.CrossRefPubMed Caminos JE, Nogueiras R, Gaytan F, Pineda R, Gonzalez CR, Barreiro ML, Castano JP, Malagon MM, Pinilla L, Toppari J, Diéguez C, Tena-Sempere M: Novel expression and direct effects of adiponectin in the rat testis. Endocrinology. 2008, 149: 3390-3402. 10.1210/en.2007-1582.CrossRefPubMed
15.
go back to reference Chabrolle C, Tosca L, Dupont J: Regulation of adiponectin and its receptors in rat ovary by human chorionic gonadotrophin treatment and potential involvement of adiponectin in granulosa cell steroidogenesis. Reproduction. 2007, 133: 719-731. 10.1530/REP-06-0244.CrossRefPubMed Chabrolle C, Tosca L, Dupont J: Regulation of adiponectin and its receptors in rat ovary by human chorionic gonadotrophin treatment and potential involvement of adiponectin in granulosa cell steroidogenesis. Reproduction. 2007, 133: 719-731. 10.1530/REP-06-0244.CrossRefPubMed
16.
go back to reference Chabrolle C, Jeanpierre E, Tosca L, Rame C, Dupont J: Effects of high levels of glucose on the steroidogenesis and the expression of adiponectin receptors in rat ovarian cells. Reprod Biol Endocrinol. 2008, 6: 11-10.1186/1477-7827-6-11.PubMedCentralCrossRefPubMed Chabrolle C, Jeanpierre E, Tosca L, Rame C, Dupont J: Effects of high levels of glucose on the steroidogenesis and the expression of adiponectin receptors in rat ovarian cells. Reprod Biol Endocrinol. 2008, 6: 11-10.1186/1477-7827-6-11.PubMedCentralCrossRefPubMed
17.
go back to reference Lagaly DV, Aad PY, Grado-Ahuir JA, Hulsey LB, Spicer LJ: Role of adiponectin in regulating ovarian theca and granulosa cell function. Mol Cell Endocrinol. 2008, 284: 38-45. 10.1016/j.mce.2008.01.007.CrossRefPubMed Lagaly DV, Aad PY, Grado-Ahuir JA, Hulsey LB, Spicer LJ: Role of adiponectin in regulating ovarian theca and granulosa cell function. Mol Cell Endocrinol. 2008, 284: 38-45. 10.1016/j.mce.2008.01.007.CrossRefPubMed
18.
go back to reference Mahesh VB, Mills TM, Bagnell CA, Conway BA: Animal models for study of polycystic ovaries and ovarian atresia. Adv Exp Med Biol. 1987, 219: 237-257.CrossRefPubMed Mahesh VB, Mills TM, Bagnell CA, Conway BA: Animal models for study of polycystic ovaries and ovarian atresia. Adv Exp Med Biol. 1987, 219: 237-257.CrossRefPubMed
19.
go back to reference Anderson E, Lee GY: The effects of dehydroepiandrosterone (DHEA) and its metabolites on the polycystic ovarian condition (PCO): cystogenic changes of rat granulosa cells in vitro. Tissue Cell. 1996, 28: 673-685. 10.1016/S0040-8166(96)80071-1.CrossRefPubMed Anderson E, Lee GY: The effects of dehydroepiandrosterone (DHEA) and its metabolites on the polycystic ovarian condition (PCO): cystogenic changes of rat granulosa cells in vitro. Tissue Cell. 1996, 28: 673-685. 10.1016/S0040-8166(96)80071-1.CrossRefPubMed
20.
go back to reference Anderson E, Lee GY: The polycystic ovarian (PCO) condition: apoptosis and epithelialization of the ovarian antral follicles are aspects of cystogenesis in the dehydroepiandrosterone (DHEA)-treated rat model. Tissue Cell. 1997, 29: 171-189. 10.1016/S0040-8166(97)80017-1.CrossRefPubMed Anderson E, Lee GY: The polycystic ovarian (PCO) condition: apoptosis and epithelialization of the ovarian antral follicles are aspects of cystogenesis in the dehydroepiandrosterone (DHEA)-treated rat model. Tissue Cell. 1997, 29: 171-189. 10.1016/S0040-8166(97)80017-1.CrossRefPubMed
21.
go back to reference Henmi H, Endo T, Nagasawa K, Hayashi T, Chida M, Akutagawa N, Iwasaki M, Kitajima Y, Kiya T, Nishikawa A, Manase K, Kudo R: Lysyl oxidase and MMP-2 expression in dehydroepiandrosterone-induced polycystic ovary in rats. Biol Reprod. 2001, 64: 157-162. 10.1095/biolreprod64.1.157.CrossRefPubMed Henmi H, Endo T, Nagasawa K, Hayashi T, Chida M, Akutagawa N, Iwasaki M, Kitajima Y, Kiya T, Nishikawa A, Manase K, Kudo R: Lysyl oxidase and MMP-2 expression in dehydroepiandrosterone-induced polycystic ovary in rats. Biol Reprod. 2001, 64: 157-162. 10.1095/biolreprod64.1.157.CrossRefPubMed
22.
go back to reference Honnma H, Endo T, Henmi H, Nagasawa K, Baba T, Yamazaki K, Kitajima Y, Hayashi T, Manase K, Saito T: Altered expression of Fas/Fas ligand/caspase 8 and membrane type 1-matrix metalloproteinase in atretic follicles within dehydroepiandrosterone-induced polycystic ovaries in rats. Apoptosis. 2006, 11: 1525-1533. 10.1007/s10495-006-9148-2.CrossRefPubMed Honnma H, Endo T, Henmi H, Nagasawa K, Baba T, Yamazaki K, Kitajima Y, Hayashi T, Manase K, Saito T: Altered expression of Fas/Fas ligand/caspase 8 and membrane type 1-matrix metalloproteinase in atretic follicles within dehydroepiandrosterone-induced polycystic ovaries in rats. Apoptosis. 2006, 11: 1525-1533. 10.1007/s10495-006-9148-2.CrossRefPubMed
23.
go back to reference Kitajima Y, Endo T, Nagasawa K, Manase K, Honnma H, Baba T, Hayashi T, Chiba H, Sawada N, Saito T: Hyperstimulation and a gonadotropin-releasing hormone agonist modulate ovarian vascular permeability by altering expression of the tight junction protein claudin-5. Endocrinology. 2006, 147: 694-699. 10.1210/en.2005-0700.CrossRefPubMed Kitajima Y, Endo T, Nagasawa K, Manase K, Honnma H, Baba T, Hayashi T, Chiba H, Sawada N, Saito T: Hyperstimulation and a gonadotropin-releasing hormone agonist modulate ovarian vascular permeability by altering expression of the tight junction protein claudin-5. Endocrinology. 2006, 147: 694-699. 10.1210/en.2005-0700.CrossRefPubMed
24.
go back to reference Hamm ML, Bhat GK, Thompson WE, Mann DR: Folliculogenesis is impaired and granulosa cell apoptosis is increased in leptin-deficient mice. Biol Reprod. 2004, 71: 66-72. 10.1095/biolreprod.104.027292.CrossRefPubMed Hamm ML, Bhat GK, Thompson WE, Mann DR: Folliculogenesis is impaired and granulosa cell apoptosis is increased in leptin-deficient mice. Biol Reprod. 2004, 71: 66-72. 10.1095/biolreprod.104.027292.CrossRefPubMed
25.
go back to reference Devine PJ, Payne CM, McCuskey MK, Hoyer PB: Ultrastructural evaluation of oocytes during atresia in rat ovarian follicles. Biol Reprod. 2000, 63: 1245-1252. 10.1095/biolreprod63.5.1245.CrossRefPubMed Devine PJ, Payne CM, McCuskey MK, Hoyer PB: Ultrastructural evaluation of oocytes during atresia in rat ovarian follicles. Biol Reprod. 2000, 63: 1245-1252. 10.1095/biolreprod63.5.1245.CrossRefPubMed
26.
go back to reference Butler WR: Nutritional interactions with reproductive performance in dairy cattle. Anim Reprod Sci. 2000, 60-61: 449-457. 10.1016/S0378-4320(00)00076-2.CrossRefPubMed Butler WR: Nutritional interactions with reproductive performance in dairy cattle. Anim Reprod Sci. 2000, 60-61: 449-457. 10.1016/S0378-4320(00)00076-2.CrossRefPubMed
27.
go back to reference Fernandez-Fernandez R, Martini AC, Navarro VM, Castellano JM, Dieguez C, Aguilar E, Pinilla L, Tena-Sempere M: Novel signals for the integration of energy balance and reproduction. Mol Cell Endocrinol. 2006, 254-255: 127-132. 10.1016/j.mce.2006.04.026.CrossRefPubMed Fernandez-Fernandez R, Martini AC, Navarro VM, Castellano JM, Dieguez C, Aguilar E, Pinilla L, Tena-Sempere M: Novel signals for the integration of energy balance and reproduction. Mol Cell Endocrinol. 2006, 254-255: 127-132. 10.1016/j.mce.2006.04.026.CrossRefPubMed
28.
go back to reference Resmini E, Andraghetti G, Rebora A, Cordera R, Vera L, Giusti M, Minuto F, Ferone D: Leptin, ghrelin, and adiponectin evaluation in transsexual subjects during hormonal treatments. J Androl. 2008, 29: 580-585. 10.2164/jandrol.108.004952.CrossRefPubMed Resmini E, Andraghetti G, Rebora A, Cordera R, Vera L, Giusti M, Minuto F, Ferone D: Leptin, ghrelin, and adiponectin evaluation in transsexual subjects during hormonal treatments. J Androl. 2008, 29: 580-585. 10.2164/jandrol.108.004952.CrossRefPubMed
29.
go back to reference Nishizawa H, Shimomura I, Kishida K, Maeda N, Kuriyama H, Nagaretani H, Matsuda M, Kondo H, Furuyama N, Kihara S, Nakamura T, Tochino Y, Funahashi T, Matsuzawa Y: Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes. 2002, 51: 2734-2741. 10.2337/diabetes.51.9.2734.CrossRefPubMed Nishizawa H, Shimomura I, Kishida K, Maeda N, Kuriyama H, Nagaretani H, Matsuda M, Kondo H, Furuyama N, Kihara S, Nakamura T, Tochino Y, Funahashi T, Matsuzawa Y: Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes. 2002, 51: 2734-2741. 10.2337/diabetes.51.9.2734.CrossRefPubMed
30.
go back to reference Luque-Ramirez M, Alvarez-Blasco F, Escobar-Morreale HF: Antiandrogenic contraceptives increase serum adiponectin in obese polycystic ovary syndrome patients. Obesity (Silver Spring). 2009, 17: 3-9. 10.1038/oby.2008.491.CrossRef Luque-Ramirez M, Alvarez-Blasco F, Escobar-Morreale HF: Antiandrogenic contraceptives increase serum adiponectin in obese polycystic ovary syndrome patients. Obesity (Silver Spring). 2009, 17: 3-9. 10.1038/oby.2008.491.CrossRef
31.
go back to reference Whitaker EM, Shaw MA, Hervey GR: Plasma oestradiol-17 beta and testosterone concentrations as possible causes of the infertility of congenitally obese Zucker rats. J Endocrinol. 1983, 99: 485-490. 10.1677/joe.0.0990485.CrossRefPubMed Whitaker EM, Shaw MA, Hervey GR: Plasma oestradiol-17 beta and testosterone concentrations as possible causes of the infertility of congenitally obese Zucker rats. J Endocrinol. 1983, 99: 485-490. 10.1677/joe.0.0990485.CrossRefPubMed
32.
go back to reference Whitaker EM, Robinson AC: Circulating reproductive hormones and hypothalamic oestradiol and progestin receptors in infertile Zucker rats. J Endocrinol. 1989, 120: 331-336. 10.1677/joe.0.1200331.CrossRefPubMed Whitaker EM, Robinson AC: Circulating reproductive hormones and hypothalamic oestradiol and progestin receptors in infertile Zucker rats. J Endocrinol. 1989, 120: 331-336. 10.1677/joe.0.1200331.CrossRefPubMed
33.
go back to reference Mitchell M, Armstrong DT, Robker RL, Norman RJ: Adipokines: implications for female fertility and obesity. Reproduction. 2005, 130: 583-597. 10.1530/rep.1.00521.CrossRefPubMed Mitchell M, Armstrong DT, Robker RL, Norman RJ: Adipokines: implications for female fertility and obesity. Reproduction. 2005, 130: 583-597. 10.1530/rep.1.00521.CrossRefPubMed
34.
go back to reference Maillard V, Uzbekova S, Guignot F, Perreau C, Rame C, Coyral Castel S, Dupont J: Effect of adiponectin on bovine granulosa cell steroidogenesis, oocyte maturation and embryo development. Reprod Biol Endocrinol. 8: 23-10.1186/1477-7827-8-23. Maillard V, Uzbekova S, Guignot F, Perreau C, Rame C, Coyral Castel S, Dupont J: Effect of adiponectin on bovine granulosa cell steroidogenesis, oocyte maturation and embryo development. Reprod Biol Endocrinol. 8: 23-10.1186/1477-7827-8-23.
Metadata
Title
Remarkable features of ovarian morphology and reproductive hormones in insulin-resistant Zucker fatty (fa/fa) rats
Authors
Hiroyuki Honnma
Toshiaki Endo
Tamotsu Kiya
Ayumi Shimizu
Kunihiko Nagasawa
Tsuyoshi Baba
Takashi Fujimoto
Hirofumi Henmi
Yoshimitsu Kitajima
Kengo Manase
Shinichi Ishioka
Eiki Ito
Tsuyoshi Saito
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2010
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-8-73

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