Endocrinol Metab.  2011 Sep;26(3):193-202. 10.3803/EnM.2011.26.3.193.

Animal Models for the Study of Polycystic Ovarian Syndrome

Affiliations
  • 1Reproductive Sciences Graduate Program, Department of Clinical Sciences, University of Kentucky, Lexington KY, USA.
  • 2Department of Animal and Food Sciences, University of Kentucky, Lexington KY, USA.
  • 3Department of Comparative Biosciences, College of Veterinary Medicine University of Illinois at Urbana-Champaign, IL, USA. jayko@illinois.edu

Abstract

No abstract available.


MeSH Terms

Animals
Models, Animal
Polycystic Ovary Syndrome

Figure

  • Fig. 1 Ultrasound image of human polycystic ovary. Ovarian cysts are shown in the periphery of the ovary as dark circles.

  • Fig. 2 Intra- and extra-ovarian factors that may elevate ovarian testosterone synthesis.

  • Fig. 3 Proposed dysregulation of HPO axis by elevated testosterone (T) level. The numbers represent sequence of events. (1) Positive estrogen (E2) feedback to E2 receptor (ER) in the hypothalamus to GnRH secretion and LH surge and progesterone (P) production in the ovary. Upon E2 stimulation, ER induces P receptor (PR) in the hypothalamus. (2) P induced suppression of GnRH secretion. (3) Hyperandrogenism-induced suppression of P receptor expression in the hypothalamus.

  • Fig. 4 Targeted modulation of ovarian steroidogenesis. A. CYP17 expression pattern in the 2-month old mouse ovary. CYP17-positve cells (theca cells; TC) are shown in brownish color. A follicle is made of oocyte (O), granulosa cells (GC) and theca cells (TC). B. ovarian steroidogenic pathway.

  • Fig. 5 Hyperandrogenic mouse ovary. 3-month old-mouse ovary stained with Hematoxylin and Eosin. Multiple early antral stage follicles and a cyst (C) are shown in the periphery of the ovary. Insert, age-matching wild type mouse ovary.

  • Fig. 6 Human polycystic ovary. A ovarian section of 41-year-old PCOS patients. Multiple cysts are shown in the periphery of the ovary. Insert, age-matching non-PCOS ovary.


Reference

1. Broekmans FJ, Knauff EA, Valkenburg O, Laven JS, Eijkemans MJ, Fauser BC. PCOS according to the Rotterdam consensus criteria: Change in prevalence among WHO-II anovulation and association with metabolic factors. BJOG. 2006. 113:1210–1217.
2. Moghetti P, Toscano V. Treatment of hirsutism and acne in hyperandrogenism. Best Pract Res Clin Endocrinol Metab. 2006. 20:221–234.
3. Shum KW, Cullen DR, Messenger AG. Hair loss in women with hyperandrogenism: four cases responding to finasteride. J Am Acad Dermatol. 2002. 47:733–739.
4. Shah B, Parnell L, Milla S, Kessler M, David R. Endometrial thickness, uterine, and ovarian ultrasonographic features in adolescents with polycystic ovarian syndrome. J Pediatr Adolesc Gynecol. 2010. 23:146–152.
5. Mitwally MF, Casper RF. Aromatase inhibition reduces the dose of gonadotropin required for controlled ovarian hyperstimulation. J Soc Gynecol Investig. 2004. 11:406–415.
6. Hall JE, Taylor AE, Hayes FJ, Crowley WF Jr. Insights into hypothalamic-pituitary dysfunction in polycystic ovary syndrome. J Endocrinol Invest. 1998. 21:602–611.
7. Barnes RB. Pathophysiology of ovarian steroid secretion in polycystic ovary syndrome. Semin Reprod Endocrinol. 1997. 15:159–168.
8. Angioni S, Portoghese E, Milano F, Melis GB, Fulghesu AM. Diagnosis of metabolic disorders in women with polycystic ovary syndrome. Obstet Gynecol Surv. 2008. 63:796–802.
9. Hoeger KM. Obesity and lifestyle management in polycystic ovary syndrome. Clin Obstet Gynecol. 2007. 50:277–294.
10. Holte J, Bergh T, Berne C, Wide L, Lithell H. Restored insulin sensitivity but persistently increased early insulin secretion after weight loss in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab. 1995. 80:2586–2593.
11. Giallauria F, Orio F, Palomba S, Lombardi G, Colao A, Vigorito C. Cardiovascular risk in women with polycystic ovary syndrome. J Cardiovasc Med (Hagerstown). 2008. 9:987–992.
12. Giallauria F, Palomba S, De Sio I, Maresca L, Vuolo L, Savastano S, Lombardi G, Colao A, Vigorito C, Orio F. Inflammatory markers and visceral fat are inversely associated with maximal oxygen consumption in women with polycystic ovary syndrome (PCOS). Clin Endocrinol (Oxf). 2009. 70:394–400.
13. Cascella T, Palomba S, De Sio I, Manguso F, Giallauria F, De Simone B, Tafuri D, Lombardi G, Colao A, Orio F. Visceral fat is associated with cardiovascular risk in women with polycystic ovary syndrome. Hum Reprod. 2008. 23:153–159.
14. Orio F, Giallauria F, Palomba S, Manguso F, Orio M, Tafuri D, Lombardi G, Carmina E, Colao A, Vigorito C. Metabolic and cardiopulmonary effects of detraining after a structured exercise training programme in young PCOS women. Clin Endocrinol (Oxf). 2008. 68:976–981.
15. Trakakis E, Balanika A, Baltas C, Loghis C, Simeonidis G, Vaggopoulos V, Papakonstantinou O, Gouliamos A, Salamalekis G, Kassanos D. Hemodynamic alterations and wall properties in large arteries of young, normotensive, and non-obese women with polycystic ovary syndrome. J Endocrinol Invest. 2008. 31:1001–1007.
16. Tremblay A, Boule N, Doucet E, Woods SC. Is the insulin resistance syndrome the price to be paid to achieve body weight stability? Int J Obes (Lond). 2005. 29:1295–1298.
17. Boule NG, Weisnagel SJ, Lakka TA, Tremblay A, Bergman RN, Rankinen T, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C. Effects of exercise training on glucose homeostasis: the HERITAGE Family Study. Diabetes Care. 2005. 28:108–114.
18. Goodyear LJ, Hirshman MF, Knutson SM, Horton ED, Horton ES. Effect of exercise training on glucose homeostasis in normal and insulin-deficient diabetic rats. J Appl Physiol. 1988. 65:844–851.
19. Sigal RJ, Kenny GP, Wasserman DH, Castaneda-Sceppa C, White RD. Physical activity/exercise and type 2 diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006. 29:1433–1438.
20. Couzinet B, Pholsena M, Young J, Schaison G. The impact of a pure anti-androgen (flutamide) on LH, FSH, androgens and clinical status in idiopathic hirsutism. Clin Endocrinol (Oxf). 1993. 39:157–162.
21. Ibanez L, de Zegher F. Low-dose flutamide-metformin therapy for hyperinsulinemic hyperandrogenism in non-obese adolescents and women. Hum Reprod Update. 2006. 12:243–252.
22. Saha L, Kaur S, Saha PK. Pharmacotherapy of polycystic ovary syndrome-an update. Fundam Clin Pharmacol. 2011.
23. Studen KB, Sebestjen M, Pfeifer M, Prezelj J. Influence of spironolactone treatment on endothelial function in non-obese women with polycystic ovary syndrome. Eur J Endocrinol. 2011. 164:389–395.
24. Armanini D, Castello R, Scaroni C, Bonanni G, Faccini G, Pellati D, Bertoldo A, Fiore C, Moghetti P. Treatment of polycystic ovary syndrome with spironolactone plus licorice. Eur J Obstet Gynecol Reprod Biol. 2007. 131:61–67.
25. Christy NA, Franks AS, Cross LB. Spironolactone for hirsutism in polycystic ovary syndrome. Ann Pharmacother. 2005. 39:1517–1521.
26. Zulian E, Sartorato P, Benedini S, Baro G, Armanini D, Mantero F, Scaroni C. Spironolactone in the treatment of polycystic ovary syndrome: effects on clinical features, insulin sensitivity and lipid profile. J Endocrinol Invest. 2005. 28:49–53.
27. Archer JS, Chang RJ. Hirsutism and acne in polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2004. 18:737–754.
28. Farhi J, Homburg R, Lerner A, Ben-Rafael Z. The choice of treatment for anovulation associated with polycystic ovary syndrome following failure to conceive with clomiphene. Hum Reprod. 1993. 8:1367–1371.
29. Marantides D. Management of polycystic ovary syndrome. Nurse Pract. 1997. 22:34–38. 40–41.
30. Homburg R. Ovulation induction. Expert Opin Pharmacother. 2003. 4:1995–2004.
31. Urman B, Yakin K. Ovulatory disorders and infertility. J Reprod Med. 2006. 51:267–282.
32. Nader S. Ovulation induction in polycystic ovary syndrome. Minerva Ginecol. 2008. 60:53–61.
33. Vause TD, Cheung AP, Sierra S, Claman P, Graham J, Guillemin JA, Lapensee L, Stewart S, Wong BC. Ovulation induction in polycystic ovary syndrome. J Obstet Gynaecol Can. 2010. 32:495–502.
34. Hart R. PCOS and infertility. Panminerva Med. 2008. 50:305–314.
35. Pasquali R, Casimirri F, Vicennati V. Weight control and its beneficial effect on fertility in women with obesity and polycystic ovary syndrome. Hum Reprod. 1997. 12:Suppl 1. 82–87.
36. Moran LJ, Norman RJ. The obese patient with infertility: a practical approach to diagnosis and treatment. Nutr Clin Care. 2002. 5:290–297.
37. Duggal PS, Ryan NK, Van der Hoek KH, Ritter LJ, Armstrong DT, Magoffin DA, Norman RJ. Effects of leptin administration and feed restriction on thecal leucocytes in the preovulatory rat ovary and the effects of leptin on meiotic maturation, granulosa cell proliferation, steroid hormone and PGE2 release in cultured rat ovarian follicles. Reproduction. 2002. 123:891–898.
38. Pasquali R, Pelusi C, Genghini S, Cacciari M, Gambineri A. Obesity and reproductive disorders in women. Hum Reprod Update. 2003. 9:359–372.
39. Pasquali R, Gambineri A. Role of changes in dietary habits in polycystic ovary syndrome. Reprod Biomed Online. 2004. 8:431–439.
40. Hoeger KM. Role of lifestyle modification in the management of polycystic ovary syndrome. Best Pract Res Clin Endocrinol Metab. 2006. 20:293–310.
41. Kolodziejczyk B, Duleba AJ, Spaczynski RZ, Pawelczyk L. Metformin therapy decreases hyperandrogenism and hyperinsulinemia in women with polycystic ovary syndrome. Fertil Steril. 2000. 73:1149–1154.
42. Awartani KA, Cheung AP. Metformin and polycystic ovary syndrome: a literature review. J Obstet Gynaecol Can. 2002. 24:393–401.
43. Barbieri RL. Metformin for the treatment of polycystic ovary syndrome. Obstet Gynecol. 2003. 101:785–793.
44. Stadtmauer L, Oehninger S. Management of infertility in women with polycystic ovary syndrome: a practical guide. Treat Endocrinol. 2005. 4:279–292.
45. Mathur R, Alexander CJ, Yano J, Trivax B, Azziz R. Use of metformin in polycystic ovary syndrome. Am J Obstet Gynecol. 2008. 199:596–609.
46. Harwood K, Vuguin P, DiMartino-Nardi J. Current approaches to the diagnosis and treatment of polycystic ovarian syndrome in youth. Horm Res. 2007. 68:209–217.
47. Boudhraa K, Jellouli MA, Amri M, Farhat M, Torkhani F, Gara MF. [Indication of metformin in the management of hormonal dysfunction secondary to polycystic ovarian syndrome: prospective comparative study of 63 cases]. Tunis Med. 2010. 88:335–340.
48. Brown J, Farquhar C, Beck J, Boothroyd C, Hughes E. Clomiphene and anti-oestrogens for ovulation induction in PCOS. Cochrane Database Syst Rev. 2009. CD002249.
49. Casper RF. Aromatase inhibitors in ovarian stimulation. J Steroid Biochem Mol Biol. 2007. 106:71–75.
50. Eckmann KR, Kockler DR. Aromatase inhibitors for ovulation and pregnancy in polycystic ovary syndrome. Ann Pharmacother. 2009. 43:1338–1346.
51. Hughes E, Brown J, Collins JJ, Vanderkerchove P. Clomiphene citrate for unexplained subfertility in women. Cochrane Database Syst Rev. 2010. CD000057.
52. Jansen RP, Handelsman DJ, Boylan LM, Conway A, Shearman RP, Fraser IS, Anderson JC. Pulsatile intravenous gonadotropin-releasing hormone for ovulation-induction in infertile women. II. Analysis of follicular and luteal phase responses. Fertil Steril. 1987. 48:39–44.
53. Larsen T, Larsen JF, Schioler V, Bostofte E, Felding C. Comparison of urinary human follicle-stimulating hormone and human menopausal gonadotropin for ovarian stimulation in polycystic ovarian syndrome. Fertil Steril. 1990. 53:426–431.
54. Nakamura Y, Yamada H, Yoshida K, Manno T, Ubukata Y, Suzuki M, Yoshimura Y. Induction of ovulation with pulsatile subcutaneous administration of human menopausal gonadotropin in patients with polycystic ovary syndrome. Horm Res. 1990. 33:Suppl 2. 43–48.
55. Cohen J. Laparoscopic procedures for treatment of infertility related to polycystic ovarian syndrome. Hum Reprod Update. 1996. 2:337–344.
56. Donesky BW, Adashi EY. Surgical ovulation induction: the role of ovarian diathermy in polycystic ovary syndrome. Baillieres Clin Endocrinol Metab. 1996. 10:293–309.
57. Liguori G, Tolino A, Moccia G, Scognamiglio G, Nappi C. Laparoscopic ovarian treatment in infertile patients with polycystic ovarian syndrome (PCOS): endocrine changes and clinical outcome. Gynecol Endocrinol. 1996. 10:257–264.
58. Tulandi T, Watkin K, Murray C, Mathur S. Reproductive Performance and Three-Dimension-Ultrasound Volume Determination of Polycystic Ovaries after Laparoscopic Ovarian Drilling. J Am Assoc Gynecol Laparosc. 1996. 3:S50–S51.
59. Farquhar C, Vandekerckhove P, Arnot M, Lilford R. Laparoscopic "drilling" by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Syst Rev. 2000. CD001122.
60. Farquhar C, Lilford RJ, Marjoribanks J, Vandekerckhove P. Laparoscopic 'drilling' by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Syst Rev. 2007. CD001122.
61. Onagbesan OM, Peddie MJ, Williams J. Regulation of cell proliferation and estrogen synthesis by ovine LH, IGF-I, and EGF in theca interstitial cells of the domestic hen cultured in defined media. Gen Comp Endocrinol. 1994. 94:261–272.
62. Jia Y, Lin J, Zeng W, Zhang C. Effect of prostaglandin on luteinizing hormone-stimulated proliferation of theca externa cells from chicken prehierarchical follicles. Prostaglandins Other Lipid Mediat. 2010. 92:77–84.
63. Palaniappan M, Menon KM. Human chorionic gonadotropin stimulates theca-interstitial cell proliferation and cell cycle regulatory proteins by a cAMP-dependent activation of AKT/mTORC1 signaling pathway. Mol Endocrinol. 2010. 24:1782–1793.
64. Kalro BN, Loucks TL, Berga SL. Neuromodulation in polycystic ovary syndrome. Obstet Gynecol Clin North Am. 2001. 28:35–62.
65. Ozawa H. Steroid Hormones, their receptors and neuroendocrine system. J Nihon Med Sch. 2005. 72:316–325.
66. Lea RW, Clark JA, Tsutsui K. Changes in central steroid receptor expression, steroid synthesis, and dopaminergic activity related to the reproductive cycle of the ring dove. Microsc Res Tech. 2001. 55:12–26.
67. Wennstrom KL, Crews D. Effect of long-term castration and long-term androgen treatment on sexually dimorphic estrogen-inducible progesterone receptor mRNA levels in the ventromedial hypothalamus of whiptail lizards. Horm Behav. 1998. 34:11–16.
68. Pastor CL, Griffin-Korf ML, Aloi JA, Evans WS, Marshall JC. Polycystic ovary syndrome: evidence for reduced sensitivity of the gonadotropin-releasing hormone pulse generator to inhibition by estradiol and progesterone. J Clin Endocrinol Metab. 1998. 83:582–590.
69. Goodman RL. Neural systems mediating the negative feedback actions of estradiol and progesterone in the ewe. Acta Neurobiol Exp (Wars). 1996. 56:727–741.
70. Heikinheimo O, Gordon K, Williams RF, Hodgen GD. Inhibition of ovulation by progestin analogs (agonists vs antagonists): preliminary evidence for different sites and mechanisms of actions. Contraception. 1996. 53:55–64.
71. Chang RJ. The reproductive phenotype in polycystic ovary syndrome. Nat Clin Pract Endocrinol Metab. 2007. 3:688–695.
72. Franco C, Bengtsson BA, Johannsson G. Visceral obesity and the role of the somatotropic axis in the development of metabolic complications. Growth Horm IGF Res. 2001. 11:Suppl A. S97–S102.
73. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev. 1997. 18:774–800.
74. Hill JW, Elias CF, Fukuda M, Williams KW, Berglund ED, Holland WL, Cho YR, Chuang JC, Xu Y, Choi M, Lauzon D, Lee CE, Coppari R, Richardson JA, Zigman JM, Chua S, Scherer PE, Lowell BB, Bruning JC, Elmquist JK. Direct insulin and leptin action on pro-opiomelanocortin neurons is required for normal glucose homeostasis and fertility. Cell Metab. 2010. 11:286–297.
75. Abbott DH, Barnett DK, Levine JE, Padmanabhan V, Dumesic DA, Jacoris S, Tarantal AF. Endocrine antecedents of polycystic ovary syndrome in fetal and infant prenatally androgenized female rhesus monkeys. Biol Reprod. 2008. 79:154–163.
76. Abbott DH, Dumesic DA, Eisner JR, Colman RJ, Kemnitz JW. Insights into the development of polycystic ovary syndrome (PCOS) from studies of prenatally androgenized female rhesus monkeys. Trends Endocrinol Metab. 1998. 9:62–67.
77. Abbott DH, Bruns CR, Barnett DK, Dunaif A, Goodfriend TL, Dumesic DA, Tarantal AF. Experimentally induced gestational androgen excess disrupts glucoregulation in rhesus monkey dams and their female offspring. Am J Physiol Endocrinol Metab. 2010. 299:E741–E751.
78. Dumesic DA, Abbott DH, Eisner JR, Goy RW. Prenatal exposure of female rhesus monkeys to testosterone propionate increases serum luteinizing hormone levels in adulthood. Fertil Steril. 1997. 67:155–163.
79. Forsdike RA, Hardy K, Bull L, Stark J, Webber LJ, Stubbs S, Robinson JE, Franks S. Disordered follicle development in ovaries of prenatally androgenized ewes. J Endocrinol. 2007. 192:421–428.
80. Manneras L, Cajander S, Holmang A, Seleskovic Z, Lystig T, Lonn M, Stener-Victorin E. A new rat model exhibiting both ovarian and metabolic characteristics of polycystic ovary syndrome. Endocrinology. 2007. 148:3781–3791.
81. Beloosesky R, Gold R, Almog B, Sasson R, Dantes A, Land-Bracha A, Hirsh L, Itskovitz-Eldor J, Lessing JB, Homburg R, Amsterdam A. Induction of polycystic ovary by testosterone in immature female rats: Modulation of apoptosis and attenuation of glucose/insulin ratio. Int J Mol Med. 2004. 14:207–215.
82. Kafali H, Iriadam M, Ozardali I, Demir N. Letrozole-induced polycystic ovaries in the rat: a new model for cystic ovarian disease. Arch Med Res. 2004. 35:103–108.
83. Lee GY, Croop JM, Anderson E. Multidrug resistance gene expression correlates with progesterone production in dehydroepiandrosterone-induced polycystic and equine chorionic gonadotropin-stimulated ovaries of prepubertal rats. Biol Reprod. 1998. 58:330–337.
84. Lee MT, Anderson E, Lee GY. Changes in ovarian morphology and serum hormones in the rat after treatment with dehydroepiandrosterone. Anat Rec. 1991. 231:185–192.
85. Motta AB. Dehydroepiandrosterone to induce murine models for the study of polycystic ovary syndrome. J Steroid Biochem Mol Biol. 2010. 119:105–111.
86. Zhang HY, Zhu FF, Xiong J, Shi XB, Fu SX. Characteristics of different phenotypes of polycystic ovary syndrome based on the Rotterdam criteria in a large-scale Chinese population. BJOG. 2009. 116:1633–1639.
87. Priyadarshani A. Relevance of an opioid, noscapine in reducing cystogeneses in rat experimental model of polycystic ovary syndrome. J Endocrinol Invest. 2009. 32:837–843.
88. Chapman JC, Min SH, Freeh SM, Michael SD. The estrogen-injected female mouse: new insight into the etiology of PCOS. Reprod Biol Endocrinol. 2009. 7:47.
89. Lee S, Kang DW, Hudgins-Spivey S, Krust A, Lee EY, Koo Y, Cheon Y, Gye MC, Chambon P, Ko C. Theca-specific estrogen receptor-alpha knockout mice lose fertility prematurely. Endocrinology. 2009. 150:3855–3862.
90. Abbott DH, Tarantal AF, Dumesic DA. Fetal, infant, adolescent and adult phenotypes of polycystic ovary syndrome in prenatally androgenized female rhesus monkeys. Am J Primatol. 2009. 71:776–784.
91. DeVane GW, Czekala NM, Judd HL, Yen SS. Circulating gonadotropins, estrogens, and androgens in polycystic ovarian disease. Am J Obstet Gynecol. 1975. 121:496–500.
92. Christian RC, Dumesic DA, Behrenbeck T, Oberg AL, Sheedy PF 2nd, Fitzpatrick LA. Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003. 88:2562–2568.
93. Phy JL, Conover CA, Abbott DH, Zschunke MA, Walker DL, Session DR, Tummon IS, Thornhill AR, Lesnick TG, Dumesic DA. Insulin and messenger ribonucleic acid expression of insulin receptor isoforms in ovarian follicles from nonhirsute ovulatory women and polycystic ovary syndrome patients. J Clin Endocrinol Metab. 2004. 89:3561–3566.
94. Foong SC, Abbott DH, Zschunke MA, Lesnick TG, Phy JL, Dumesic DA. Follicle luteinization in hyperandrogenic follicles of polycystic ovary syndrome patients undergoing gonadotropin therapy for in vitro fertilization. J Clin Endocrinol Metab. 2006. 91:2327–2333.
95. Vrbikova J, Hainer V. Obesity and polycystic ovary syndrome. Obes Facts. 2009. 2:26–35.
96. Sozen I, Arici A. Hyperinsulinism and its interaction with hyperandrogenism in polycystic ovary syndrome. Obstet Gynecol Surv. 2000. 55:321–328.
97. Kopelman PG. Hormones and obesity. Baillieres Clin Endocrinol Metab. 1994. 8:549–575.
98. Couse JF, Lindzey J, Grandien K, Gustafsson JA, Korach KS. Tissue distribution and quantitative analysis of estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) messenger ribonucleic acid in the wild-type and ERalpha-knockout mouse. Endocrinology. 1997. 138:4613–4621.
99. Hatoya S, Torii R, Kumagai D, Sugiura K, Kawate N, Tamada H, Sawada T, Inaba T. Expression of estrogen receptor alpha and beta genes in the mediobasal hypothalamus, pituitary and ovary during the canine estrous cycle. Neurosci Lett. 2003. 347:131–135.
100. Bridges PJ, Koo Y, Kang DW, Hudgins-Spivey S, Lan ZJ, Xu X, DeMayo F, Cooney A, Ko C. Generation of Cyp17iCre transgenic mice and their application to conditionally delete estrogen receptor alpha (Esr1) from the ovary and testis. Genesis. 2008. 46:499–505.
Full Text Links
  • ENM
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr