1. Azziz R, Marin C, Hoq L, Badamgarav E, Song P. Health care-related economic burden of the polycystic ovary syndrome during the reproductive life span. J Clin Endocrinol Metab. 2005;90:4650–4658. [PubMed] 2. The Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group: Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS) Hum Reprod. 2004;19:41–47. [PubMed] 3. Barnes RB, Rosenfield RL, Ehrmann DA, Cara JF, Cuttler L, Levitsky LL, Rosenthal IM. Ovarian hyperandrogynism as a result of congenital adrenal virilizing disorders: evidence for perinatal masculinization of neuroendocrine function in women. J Clin Endocrinol Metab. 1994;79:1328–1333. [PubMed] 4. Merke DP, Cutler GB., Jr New ideas for medical treatment of congenital adrenal hyperplasia. Endocrinol Metab Clin North Am. 2001;30:121–135. [PubMed] 5. Phocas I, Chryssikopoulos A, Sarandakou A, Rizos D, Trakakis E. A contribution to the classification of cases of non-classic 21-hydroxylase-deficient congenital adrenal hyperplasia. Gynecol Endocrinol. 1995;9:229–238. [PubMed] 6. Stikkelbroeck NM, Hermus AR, Braat DD, Otten BJ. Fertility in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Obstet Gynecol Surv. 2003;58:275–284. [PubMed] 7. Clarke IJ, Scaramuzzi RJ, Short RV. Ovulation in prenatally androgenized ewes. J Endocrinol. 1977;73:385–389. [PubMed] 8. Birch RA, Padmanabhan V, Foster DL, Unsworth WP, Robinson JE. Prenatal programming of reproductive neuroendocrine function: fetal androgen exposure produces progressive disruption of reproductive cycles in sheep. Endocrinology. 2003;144:1426–1434. [PubMed] 9. Abbott DH, Foong SC, Barnett DK, Dumesic DA. Nonhuman primates contribute unique understanding to anovulatory infertility in women. ILAR. 2004;45:116–131. [PubMed] 10. Recabarren SE, Padmanabhan V, Codner E, Lobos A, Durán C, Vidal M, Foster DL, Sir-Petermann T. Postnatal developmental consequences of altered insulin sensitivity in female sheep treated prenatally with testosterone. Am J Physiol. 2005;289:E801–E806. [PubMed] 11. Abbott DH, Barnett DK, Bruns CM, Dumesic DA. Androgen excess fetal programming of female reproduction: a developmental aetiology for polycystic ovary syndrome? Hum Reprod Update. 2005;11:357–374. [PubMed] 12. Fabre-Nys C, Venier G. Sexual differentiation of sexual behavior and preovulatory LH surge in ewes. Psychoneuroendocr. 1991;16:383–396. [PubMed] 13. Sharma TP, Herkimer C, West C, Ye W, Birch R, Robinson JE, Foster DL, Padmanabhan V. Fetal programming: prenatal androgen disrupts positive feedback actions of estradiol but does not affect timing of puberty in female sheep. Biol Reprod. 2002;66:924–933. [PubMed] 14. Sarma HN, Manikkam M, Herkimer C, Dell’Orco J, Welch KB, Foster DL, Padmanabhan V. Fetal programming: excess prenatal testosterone reduces postnatal luteinizing hormone, but not follicle-stimulating hormone responsiveness, to estradiol negative feedback in the female. Endocrinology. 2005;146:4281–4491. [PubMed] 15. 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. [PubMed] 16. Wood RI, Foster DL. Sexual differentiation of reproductive neuroendocrine function in sheep Rev Reprod. 1998;3:130–140. [PubMed] 17. Robinson JE, Forsdike RA, Taylor JA. In utero exposure of female lambs to testosterone reduces the sensitivity of the gonadotropin-releasing hormone neuronal network to inhibition by progesterone. Endocrinology. 1999;140:5797–5805. [PubMed] 18. Robinson JE, Birch RA, Foster DL, Padmanabhan V. Prenatal exposure of the ovine fetus to androgens sexually differentiates the steroid feedback mechanisms that control gonadotropin releasing hormone secretion and disrupts ovarian cycles. Arch Sex Behav. 2002;31:35–41. [PubMed] 19. Unsworth WP, Taylor JA, Robinson JE. Prenatal programming of reproductive neuroendocrine function: the effect of prenatal androgens on the development of estrogen positive feedback and ovarian cycles in the ewe. Biol Reprod. 2005;72:619–627. [PubMed] 20. Dumesic DA, Schramm RD, Peterson E, Paprocki AM, Zhou R, Abbott DH. Impaired developmental competence of oocytes in adult prenatally androgenized female rhesus monkeys undergoing gonadotropin stimulation for in vitro fertilization. J Clin Endocrinol Metab. 2002;87:1111–1119. [PubMed] 21. Steiner RA, Clifton DK, Spies HG, Resko JA. Sexual differentiation and feedback control of luteinizing hormone secretion in the rhesus monkey. Biol Reprod. 1976;15:206–212. [PubMed] 22. Eisner JR, Barnett MA, Dumesic DA, Abbott DH. Ovarian hyperandrogenism in adult female rhesus monkeys exposed to prenatal androgen excess. Fertil Steril. 2002;77:167–172. [PubMed] 23. Zhou R, Bird IM, Dumesic DA, Abbott DH. Adrenal hyperandrogenism is induced by fetal androgen excess in a rhesus monkey model of polycystic ovary syndrome. J Clin Endocrinol Metab. 2005;90:6630–6637. [PMC free article] [PubMed] 24. Padmanabhan V, Manikkam M, Recabarren S, Foster D. Prenatal testosterone excess programs reproductive and metabolic dysfunction in the female. Mol Cell Endocrinol. 2006;246:165–174. [PubMed]
25. Manikkam M, Steckler T, Padmanabhan V. Developmental programming: prenatal testosterone excess increases ovarian androgen receptors in fetal sheep. 40th Annual Meeting of the Society for the Study of Reproduction; July 22–25 2007; San Antonio, Tx.
26. West C, Foster DL, Evans NP, Robinson J, Padmanabhan V. Intra-follicular activin availability is altered in prenatally-androgenized lambs. Mol Cell Endocrinol. 2001;185:51–59. [PubMed]
27. Abbott DH, Colman RJ, Kemnitz JW, Eisner JR, Dumesic DA. Prenatal androgen excess programs for polycystic ovarian syndrome in female rhesus monkeys. In: Chang J, Heindel JJ, Dunaif A, editors. Polycystic Ovary Syndrome. New York: Marcel Dekker, Inc, New York; 2002A. pp. 119–133.
28. Nelson VL, Legro RS, Strauss JF, III, McAllister JM. Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries. Mol Endocrinol. 1999;13:946–957. [PubMed] 29. Nelson VL, Qin K, Rosenfield RL, Wood JR, Penning TM, Legro RS, Strauss JF, III, McAllister JM. The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2001;86:5925–5933. [PubMed] 30. Carmina E, Chu MC, Longo RA, Rini GB, Lobo RA. Phenotypic variation in hyperandrogenic women influences the findings of abnormal metabolic and cardiovascular risk parameters. J Clin Endocrinol Metab. 2005;90:2545–2549. [PubMed]
31. Padmanabhan V, Veiga-Lopez A, Abbott DH, Dumesic DA. Developmental programming of ovarian disruption. In: Gonzalez-Bulnes A, editor. Novel Concepts in Ovarian Endocrinology. India: Research Signpost; 2007. in press.
32. 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. [PubMed] 33. Manikkam M, Steckler TL, Welch KB, Inskeep EK, Padmanabhan V. Fetal programming: prenatal testosterone treatment leads to follicular persistence/luteal defects. Partial restoration of ovarian function by cyclic progesterone treatment. Endocrinology. 2006;147:1997–2007. [PubMed] 34. Sullivan SD, Moenter SM. Prenatal androgens alter GABAergic drive to gonadotropin-releasing hormone neurons: implications for a common fertility disorder. Proc Natl Acad Sci USA. 2004;101:7129–7134. [PubMed] 35. Foecking EM, Szabo M, Schwartz NB, Levine JF. Neuroendocrine consequences of prenatal androgen exposure in the female rat: absence of luteinizing hormone surges, suppression of progesterone receptor gene expression, and acceleration of the gonadotropin-releasing hormone pulse generator. Biol Reprod. 2005;72:1475–1483. [PubMed]
36. Abbott DH, Dumesic DA, Eisner JR, Kemnitz JW, Goy RW. The prenatally androgenized female rhesus monkey as a model for PCOS. In: Azziz R, Nestler JE, Dewailly D, editors. Androgen Excess Disorders in Women. Philadelphia: Lippincott-Raven; 1997. pp. 369–382.
37. Resko JA, Ellinwood WE. Sexual differentiation of the brain of primates. In: Serio M, Motta M, Zanisi M, Martini L, editors. Sexual Differentiation: Basic and Clinical Aspects. New York: Raven Press; 1984. pp. 169–181.
38. Resko JA, Buhl AE, Phoenix CH. Treatment of pregnant rhesus macaques with testosterone propionate: observations on its fate in the fetus. Biol Reprod. 1987;37:1185–1191. [PubMed]
39. Abbott DH, Bruns CM, Barnett DK, Dumesic DA. Fetal programming of polycystic ovary syndrome. In: Kovacs G, Norman R, editors. Polycystic Ovary Syndrome. 2nd Edition. Cambridge: Cambridge University Press; 2007. pp. 262–287.
40. Foster DL, Jackson LM, Padmanabhan V. Programming of GnRH feedback controls timing puberty and adult reproductive activity. Mol Cell Endocrinology. 2006;254–255:109–119. [PubMed] 41. Hughesdon PE. Morphology and morphogenesis of the Stein-Leventhal ovary and of so-called “hyperthecosis.” Obstet Gynecol Survey. 1982;37:59–77. [PubMed] 42. Maciel GA, Baracat EC, Benda JA, Markham SM, Hensinger K, Chang RJ, Erickson G. Stockpiling of transitional and classic primary follicles in ovaries of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2004;89:5321–5327. [PubMed] 43. Webber LJ, Stubbs S, Stark J, Trew GH, Margara R, Hardy K, Franks S. Formation and early development of follicles in the polycystic ovary. Lancet. 2003;362:1017–1021. [PubMed] 44. Vendola KA, Zhou J, Adesanya OO, Weil SJ, Bondy CA. Androgens stimulate early stages of follicle growth in the primate ovarian. J Clin Invest. 1998;101:2622–2629. [PMC free article] [PubMed] 45. Weil SJ, Vendola K, Zhou J, Adesanya OO, Wang J, Okafor J, Bondy CA. Androgen receptor gene expression in the primate ovary: cellular localization, regulation, and functional correlations. J Clin Endocrinol Metab. 1998;83:2479–2485. [PubMed] 46. Weil S, Vendola K, Zhou J, Bondy CA. Androgen and follicle-stimulating hormone interactions in primate ovarian follicle development. J Clin Endocrinol Metab. 1999;84:2951–2956. [PubMed] 47. Vendola K, Zhou J, Wang J, Bondy CA. Androgens promote insulin-like growth factor-I and insulin-like growth factor-I receptor gene expression in the primate ovary. Hum Reprod. 1999A;14:2328–2332. [PubMed] 48. Vendola K, Zhou J, Wang J, Famuyiwa OA, Bievre M, Bondy CA. Androgens promote oocyte insulin-like growth factor I expression and initiation of follicle development in the primate ovary. Biol Reprod. 1999B;61:353–357. [PubMed] 49. Steckler T, Wang J, Bartol FF, Roy SK, Padmanabhan V. Fetal programming: prenatal testosterone treatment causes intrauterine growth retardation, reduces ovarian reserve and increases ovarian follicular recruitment. Endocrinology. 2005;146:3185–3193. [PubMed] 50. Gougeon A. Regulation of ovarian follicular development in primates: facts and hypothesis. Endo Rev. 1996;17:121–155. [PubMed] 51. Jakimiuk AJ, Weitsman SR, Brzechffa PR, Magoffin DA. Aromatase mRNA expression in individual follicles from polycystic ovaries. Mol Hum Reprod. 1998;4:1–8. [PubMed] 52. Padmanabhan V, Christman GM, Randolph JF, Kelch RP, Marshall JC, Beitins IZ. Dynamics of bioactive FSH secretion in women with polycystic ovarian syndrome (PCOS): effects of estradiol and progesterone. Fertility and Sterility. 2001;75:881–888. [PubMed] 53. Erickson GF, Magoffin DA, Garzo VG, Cheung AP, Chang RJ. Granulosa cells of polycystic ovaries: are they normal or abnormal? Hum Reprod. 1992;7:293–299. [PubMed] 54. Mason HD, Willis DS, Beard RW, Winston RM, Margara R, Franks S. Estradiol production by granulosa cells of normal and polycystic ovaries: relationship to menstrual cycle history and concentrations of gonadotropins and sex steroids in follicular fluid. J Clin Endocrinol Metab. 1994;79:1355–1360. [PubMed] 55. Jonard S, Robert Y, Cortet-Rudelli C, Pigny P, Decanter C, Dewailly D. Ultrasound examination of polycystic ovaries: is it worth counting the follicles? Hum Reprod. 2003;18:598–603. [PubMed] 56. Jakimiuk AJ, Weitsman SR, Magoffin DA. 5α-Reductase activity in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 1999;84:2414–2418. [PubMed] 57. Agarwal SK, Judd HL, Magoffin DA. A mechanism for the suppression of estrogen production in polycystic ovary syndrome. J Clin Endocrinol Metab. 1996;81:3686–3691. [PubMed] 58. Dumesic DA, Schramm RD, Bird IM, Peterson E, Paprocki AM, Zhou R, Abbott DH. Reduced intrafollicular androstenedione and estradiol levels in early-treated prenatally androgenized female rhesus monkeys receiving FSH therapy for in vitro fertilization. Biol Reprod. 2003;69 1213–121. [PubMed] 59. Zeleznik AJ, Little-Ihrig L, Ramasawamy S. Administration of dihydrotestosterone to rhesus monkeys inhibits gonadotropin-stimulated ovarian steroidogenesis. J Clin Endocrinol Metab. 2004;89:860–866. [PubMed] 60. Pradeep PK, Li X, Peegel H, Menon KMJ. Dihydrotestosterone inhibits granulosa cell proliferation by decreasing the cyclin D2 mRNA expression and cell cycle arrest at G1 phase. Endocrinology. 2002;143:2930–2935. [PubMed] 61. Franks S, Gilling-Smith C, Watson H, Willis D. Insulin action in the normal and polycystic ovary. Endocrinol Metab Clin North Am. 1999;28:361–378. [PubMed] 62. Legro RS, Bentley-Lewis R, Driscoll D, Wang SC, Dunaif A. Insulin resistance in the sisters of women with polycystic ovary syndrome: association with hyperandrogenemia rather than menstrual irregularity. J Clin Endocrinol Metab. 2002;87:2128–2133. [PubMed] 63. Clark AM, Thornley B, Tomlinson L, Galletley C, Norman RJ. Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum Reprod. 1998;13:1502–1505. [PubMed] 64. Willis D, Franks S. Insulin action in human granulosa cells from normal and polycystic ovaries is mediated by the insulin receptor and not the type-1 insulin-like growth factor receptor. J Clin Endocrinol Metab. 1995;80:3788–3790. [PubMed] 65. Willis D, Mason H, Gilling-Smith C, Franks S. Modulation by insulin of follicle-stimulating hormone and luteinizing hormone actions in human granulosa cells of normal and polycystic ovaries. J Clin Endocrinol Metab. 1996;81:302–309. [PubMed] 66. Willis D, Watson H, Mason H, Galea R, Brincat M, Franks S. Premature response to LH of granulosa cells from anovulatory women with polycystic ovaries: relevance to mechanism of anovulation. J Clin Endocrinol Metab. 1998;83:3984–3991. [PubMed] 67. Jakimiuk AJ, Weitsman SR, Navab A, Magoffin DA. Luteinizing hormone receptor, steroidogenesis acute regulatory protein, and steroidogenic enzyme messenger ribonucleic acids are overproduced in thecal and granulosa cells from polycystic ovaries. J Clin Metab Endocrinol. 2001;86:1318–1323. [PubMed] 68. Franks S, Mason H, Willis D. Follicular dynamics in the polycystic ovary syndrome. Mol Cell Endocrinol. 2000;163:49–52. [PubMed] 69. Dumesic DA, Schramm RD, Peterson E, Paprocki AM, Zhou R, Abbott DH. Impaired developmental competence of oocytes in adult prenatally androgenized female rhesus monkeys undergoing gonadotropin stimulation for in vitro fertilization. J Clin Endocrinol Metab. 2002;87:1111–1119. [PubMed] 70. Dunaif A, Scott D, Finegood D, Quintana B, Whitcomb R. The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome. J Clin Endocrinol Metab. 1996;81:3299–3306. [PubMed] 71. Norman RJ, Kidson WJ, Cuneo RC, Zacharin MR. Metformin and intervention in polycystic ovary syndrome. MJA. 2001;174:580–583. [PubMed] 72. Lord JM, Flight IHK, Norman RJ. Metformin in polycystic ovary syndrome: systematic review and meta-analysis. BMJ. 2003;327:1–6. [PMC free article] [PubMed] 73. Zhou R, Bruns CM, Bird IM, Kemnitz JW, Goodfriend TL, Dumesic DA, Abbott DA. Pioglitazone improves insulin action and normalizes menstrual cycles in a nonhuman primate model of polycystic ovary syndrome. Reprod Toxicol. 2007;23:438–448. [PMC free article] [PubMed] 74. Sadatsuki M, Tsutsumi O, Yamada R, Muramatsu M, Taketani Y. Local regulatory effects of activin A and follistatin on meiotic maturation of rat oocytes. Biochem Biophys Res Commun. 1993;196:388–395. [PubMed] 75. Knight PG, Glister C. Potential local regulatory functions of inhibins, activins and follistatin in the ovary. Reproduction. 2001;121:503–512. [PubMed] 76. Schneyer AL, Fujiwara T, Fox J, Welt CK, Adams J, Messerlian GM, Taylor AE. Dynamic changes in the intrafollicular inhibin/activin/follistatin axis during human follicular development: relationship to circulating hormone levels. J Clin Endocrinol Metab. 2000;85:3319–3330. [PubMed] 77. Lambert-Messerlian G, Taylor A, Leykin L, Isaacson K, Toth T, Chang Y, Schneyer A. Characterization of intrafollicular steroid hormones, inhibin, and follistatin in women with and without polycystic ovarian syndrome following gonadotropin stimulation. Biol Reprod. 1997;57:1211–1216. [PubMed] 78. Magoffin DA, Jakimiuk AJ, Inhibin A. inhibin B and activin concentrations in follicular fluid from women with polycystic ovary syndrome. Hum Reprod. 1998;13:2693–2698. [PubMed] 79. Welt CK, Taylor AE, Fox J, Messerlian GM, Adams JM, Schneyer AL. Follicular arrest in polycystic ovary syndrome is associated with deficient inhibin A and B biosynthesis. J Clin Endocrinol Metab. 2005;90:5582–5587. [PubMed] 80. Norman RJ, Milner CR, Groome NP, Robertson DM. Circulating follistatin concentrations are higher and activin levels are lower in polycystic ovarian syndrome. Hum Reprod. 2001;16:668–672. [PubMed] 81. Eldar-Geva T, Spitz IM, Groome NP, Margalioth EJ, Homberg R. Follistatin and activin A serum concentrations in obese and non-obese patients with polycystic ovary syndrome. Hum Reprod. 2001;16:2552–2556. [PubMed] 82. Kipp JL, Kilen SM, Bristol-Gould S, Woodruff TK, Mayo KE. Neonatal exposure to estrogens suppresses activin expression and signaling in the mouse ovary. Endocrinology. 2007;148:1968–1976. [PubMed]
83. Lobo RA. The syndrome of hyperandrogenic chronic anovulation. In: Mishell DR Jr, Davajan V, Lobo RA, editors. Infertility, Contraception and Reproductive Endocrinology. Third Edition. Cambridge: Blackwell Scientific Publications; 1991. pp. 447–487.
84. Waldstreicher J, Santoro NF, Hall JE, Filicori M, Crowley WF., Jr Hyperfunction of the hypothalamic-pituitary axis in women with polycystic ovarian disease: indirect evidence for partial gonadotroph desensitization. J Clin Endocrinol Metab. 1988;66:165–172. [PubMed] 85. Rosenfield RL, Barnes RB, Cara JF, Lucky AW. Dysregulation of cytochrome P450c17a as the cause of polycystic ovarian syndrome. Fertil Steril. 1990;53:785–791. [PubMed] 86. Marshall J, Eagleson C, McCartney C. Neuroendocrine aspects of polycystic ovary syndrome. Endocrinol Metab Clin North Am. 1999;28:295–324. [PubMed] 87. Chhabra S, McCartney CR, Yoo RY, Eagleson CA, Chang RJ, Marshall JC. Progesterone inhibition of the hypothalamic gonadotropin-releasing hormone pulse generator: evidence for varied effects in hyperandrogenic adolescent girls. J Clin Endocrinol Metab. 2005;90:2810–2815. [PubMed] 88. Eagleson CA, Gingrich MB, Pastor CL, Arora TK, Burt CM, Evans WS, Marshall JC. Polycystic ovarian syndrome: evidence that flutamide restores sensitivity of the gonadotropin-releasing hormone pulse generator to inhibition by estradiol and progesterone. J Clin Endocrinol Metab. 2000;85:4047–4052. [PubMed] 89. Wood RI, Mehta V, Herbosa CG, Foster DL. Prenatal testosterone differentially masculinizes tonic and surge modes of luteinizing hormone secretion in the developing sheep. Neuroendocrinology. 1995;62:238–247. [PubMed] 90. Foster DL, Padmanabhan V, Wood RI, Robinson JE. Sexual differentiation of the neuroendocrine control of gonadotrophin secretion: concepts derived from sheep models. Reprod Suppl. 2002;59:83–99. [PubMed] 91. Buhl AE, Norman RL, Resko JA. Sex differences in estrogen-induced gonadotropin release in hamsters. Biol Reprod. 1978;18:592–597. [PubMed]
92. Levine JE, Terasawa E, Hoffman SM, Dobbert MJW, Foecking EM, Abbott DH. Luteinizing hormone (LH) hypersecretion and diminished LH responses to RU486 in a nonhuman primate model for polycystic ovary syndrome (PCOS) Abstract P1-85. 87th Annual Meeting of the Endocrine Society. 2005:4–7. San Diego, CA, June.
93. Flak J, Herkimer C, Han D, Padmanabhan V. Fetal programming: Prenatal testosterone treatment, by its androgenic action, programs adult hypergonadotropism partly by increasing pituitary sensitivity to GnRH. Abstract. 2005;143:113. Biol Rep Special Issue.
94. Esinler I, Bayar U, Bozdag G, Yarali H. Outcome of intracytoplasmic sperm injection in patients with polycystic ovary syndrome or isolated polycystic ovaries. Fertil Steril. 2005;84:932–937. [PubMed] 95. Heijnen EMEW, Eijkemans MJC, Hughes EG, Laven JSE, Macklon NS, Fauser BCJM. A meta-analysis of outcomes of conventional IVF in women with polycstic ovary syndrome. Human Reprod Update. 2006;12:13–21. [PubMed] 96. Lu XE, Yang XF, Li MG, Zhou FZ, Zhu YM, Huang HF. Outcome of in vitro fertilization-embryo transfer in treatment of polycystic ovarian syndrome. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2006;35:319–322. [PubMed] 97. Ludwig M, Finas DF, Al-Hasani S, Diedrich K, Ortmann O. Oocyte quality and treatment outcome in intracytoplasmic sperm injection cycles of polycystic ovarian syndrome patients. Hum Reprod. 1999;14:354–358. [PubMed] 98. Hwang JL, Seow KM, Lin YH, Hsieh BC, Huang LW, Chen HJ, Huang SC, Chen CY, Chen PH, Tzeng CR. IVF versus ICSI in sibling oocytes from patients with polycystic ovarian syndrome: a randomized controlled trial. Hum Reprod. 2005;20:1261–1265. [PubMed] 99. Sengoku K, Tamate K, Takuma N, Yoshida T, Goishi K, Ishikawa M. The chromosomal normality of unfertilized oocytes from patients with polycystic ovarian syndrome. Hum Reprod. 1997;12:474–477. [PubMed] 100. Kodama H, Fukuda J, Karube H, Matsui T, Shimizu Y, Tanaka T. High incidence of embryo transfer cancellations in patients with polycystic ovary syndrome. Hum Reprod. 1995;10:1962–1967. [PubMed] 101. Cano F, Garcia-Velasco JA, Millet A, Remohi J, Simon C, Pellicer A. Oocyte quality in polycystic ovaries revisited: identification of a particular subgroup of women. J Assist Reprod Genet. 1997;14:254–260. [PMC free article] [PubMed] 102. Foong SC, Abbott DH, Zschunke MA, Lesnick TG, Phy JL, Dumesic DA. Follicle luteinization in hyperandrogenic follicles of polycystic ovary syndrome (PCOS) patients undergoing gonadotropin therapy for in vitro fertilization. J Clin Endocrinol Metab. 2006;91:2327–2333. [PubMed] 103. Wood JR, Dumesic DA, Abbott DH, Strauss JF. Molecular abnormalities in oocytes from women with polycystic ovary syndrome revealed by microarray analysis. J Clin Endocrinol Metab. 2007;92:705–713. [PubMed] 104. Tesarik J, Mendoza C. Nongenomic effects of 17β -estradiol on maturing human oocytes: relationship to oocyte developmental potential. J Clin Endocrinol Metab. 1995;80:1438–1443. [PubMed] 105. Zheng P, Wei S, Bavister BD, Yang J, Ding C, Ji W. 17β-estradiol and progesterone improve in-vitro cytoplasmic maturation of oocytes from unstimulated prepubertal and adult rhesus monkeys. Hum Reprod. 2003;18:2137–2144. [PubMed] 106. Kreiner D, Liu HC, Itskovitz J, Veeck L, Rosenwaks Z. Follicular fluid estradiol and progesterone are markers of preovulatory oocyte quality. Fertil Steril. 1987;48:991–994. [PubMed] 107. Eppig JJ, O’Brien MJ, Pendola FL, Watanabe S. Factors affecting the developmental competence of mouse oocytes grown in vitro: follicle stimulating hormone and insulin. Biol Reprod. 1998;59:1445–1453. [PubMed] 108. Foong SC, Abbott DH, Lesnick TG, Session DR, Walker DL, Dumesic DA. Diminished intrafollicular estradiol (E2) levels in women with reduced ovarian responsiveness to recombinant human follicle stimulating hormone (FSH) therapy for in vitro fertilization (IVF) Fertil Steril. 2005;83:1377–1383. [PubMed] 109. Hillier SG, Whitelaw PF, Smyth CD. Follicular oestrogen synthesis: the ‘two-cell, two-gonadotropin’ model revisited. Mol Cell Endocrinol. 1994;100:51–54. [PubMed] 110. Tesarik J, Mendoza C. Direct non-genomic effects of follicular steroids on maturing human oocytes: oestrogen versus androgen antagonism. Hum Reprod Update. 1997;3:95–100. [PubMed] 111. Yding Andersen C. Characteristics of human follicular fluid associated with successful conception after in vitro fertilization. J Clin Endocrinol Metab. 1993;77:1227–1234. [PubMed] 112. Steckler TL, Robertts EK, Doop DD, Lee TM, Padmanabhan V. Developmental programming in sheep: administration of testosterone during 60–90 days of pregnancy reduces breeding success and pregnancy outcome. Theriogenology. 2007;67:459–467. [PubMed]
113. Wild RA. Hyperandrogenism: Implications for cardiovascular, endometrial, and breast disease. In: Adashi EY, Rock JA, Rosenwaks Z, editors. Reproductive Endocrinology, Surgery, and Technology’. Philadelphia: Lippincott-Raven Publishers; 1996. pp. 1617–1634.
114. Dunaif A. Insulin resistance and the polycystic ovarian syndrome: mechanism and implications for pathogenesis. Endocr Rev. 1997;18:774–800. [PubMed] 115. 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. [PubMed] 116. Waterworth DM, Bennett ST, Gharani N, McCarthy M, Hague S, Batty S, Conway GS, White DW, Todd JA, Franks S, Williamson R. Linkage and association of insulin gene VNTR regulatory polymorphism with polycystic ovary syndrome. Lancet. 1997;349:986–990. [PubMed] 117. Urbanek M, Legro RS, Driscoll D, Strauss JF, Dunaif A, Spielman RS. Searching for the polycystic ovary syndrome genes. J Pediatr Endocrinol. 2000;13 Suppl.5:1311–1313. [PubMed] 118. Tucci S, Futterweit W, Concepcion ES, Greenberg DA, Villanueva R, Davies TF, Tomer Y. Evidence for association of polycystic ovary syndrome in Caucasian women with a marker at the insulin receptor gene locus. J Clin Endocrinol Metab. 2001;86:446–449. [PubMed] 119. Diamanti-Kandarakis E, Mitrakou A, Hennes MMI, Platanissiotis D, Kaklas N, Spina J, Georgiadou E, Hoffmann RG, Kissebah AH, Raptis S. Insulin sensitivity and antiandrogen therapy in women with polycystic ovary syndrome. Metabolism. 1995;44:525–531. [PubMed] 120. Holte J, Bergh T, Berne CH, Berglund L, Lithell H. Enhanced early insulin response to glucose in relation to insulin resistance in women with polycystic ovary syndrome and normal glucose tolerance. J Clin Endocrinol Metab. 1994;78:1052–1058. [PubMed] 121. Vrbikova J, Cibula D, Dvorakova K, Stanicka S, Sindelka G, Hill M, Fanta M, Vondra K, Skrha J. Insulin sensitivity in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2004;89:2942–2945. [PubMed] 122. Coviello AD, Legro RS, Dunaif A. Adolescent girls with polycystic ovary syndrome have an increased risk of metabolic syndrome associated with increasing androgen levels independent of obesity and insulin resistance. J Clin Endocrinol Metab. 2006;91:492–497. [PubMed] 123. Kemnitz JW, Goy RW, Flitsch TJ, Lohmiller JJ, Robinson JA. Obesity in male and female rhesus monkeys: fat distribution, glucoregulation, and serum androgen levels. J Clin Endocrinol Metab. 1989;69:287–293. [PubMed] 124. Eisner JR, Dumesic DA, Kemnitz JW, Abbott DH. Timing of prenatal androgen excess determines differential impairment in insulin secretion and action in adult female rhesus monkeys. J Clin Endocrinol Metab. 2000;85:1206–1210. [PubMed] 125. Eisner JR, Dumesic DA, Kemnitz JW, Colman RJ, Abbott DH. Increased adiposity in female rhesus monkeys exposed to androgen excess during early gestation. Obes Res. 2003;11:279–286. [PubMed] 126. Bruns CM, Baum ST, Colman RJ, Dumesic DA, Eisner JR, Jensen MD, Whigham LD, Abbott DH. Prenatal androgen excess negatively impacts body fat distribution in a nonhuman primate model of polycystic ovary syndrome (PCOS) Int J of Obesity. in press [PMC free article] [PubMed]
127. Abbott DH, Eisner JR, Goodfriend T, Medley RD, Peterson EJ, Colman RJ, Kemnitz JW, Dumesic DA. Leptin and total free fatty acids are elevated in the circulation of prenatally androgenized female rhesus monkeys. 84rd Annual Meeting of The Endocrine Society; June 19–22, 2002B; San Francisco, CA. pp. 19–22. Abstract P2-329.
128. King AJ, Olivier NB, Mohankumar PS, Lee JS, Padmanabhan V, Fink GD. Hypertension caused by prenatal testosterone excess in female sheep. Am J Physiol Endocrinol Metab. 2007 Feb 27; [Epub ahead of print] PMID: 17327368. [PubMed] 129. Brettenthaler N, De Geyter C, Huber PR, Keller U. Effect of the insulin sensitizer pioglitazone on insulin resistance, hyperandrogenism, and ovulatory dysfunction in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2004;89:3835–3840. [PubMed] 130. Baillargeon JP, Jakubowicz DJ, Iuorno MJ, Jakubowicz S, Nestler JE. Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity. Fertil Steril. 2004;82:893–902. [PubMed]
131. Lee JS, Aizenberg E, Djoumbi D, Foster DL, Padmanabhan V. Fetal programming of the postnatal responsiveness of LH to estradiol negative feedback in sheep: time and duration of exposure and quality of prenatal steroid. Abstract. 2005;660(Biol Rep Special Issue):227.
132. Barker DJP. Fetal programming of coronary heart disease. Trends Endocrinol Metab. 2002;13:364–368. [PubMed] 133. Neel JV. Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”? Am J Hum Genet. 1962;14:353–362. [PubMed] 134. De Boo HA, Harding JE. The developmental origins of adult disease (Barker) hypothesis. Aust N Z J Obstet Gynaecol. 2006;46:4–14. [PubMed] 135. Ibanez L, Potau N, Zampolli M, Prat N, Virdis R, Vicens-Calvet E, Carrascosa A. Hyperinsulinemia in postpubertal girls with a history of premature pubarche and functional ovarian hyperandrogenism. J Clin Endocrinol Metab. 1996;81:1237–1243. [PubMed] 136. Sir-Petermann T, Hitchsfeld C, Maliqueo M, Codner E, Echiburu B, Gazitua R, Recabarren S, Cassorla F. Birth weight in offspring of mothers with polycystic ovarian syndrome. Hum Reprod. 2005;20:2122–2126. [PubMed] 137. Laitinen J, Taponen S, Martikainen H, Pouta A, Millwood I, Hartikainen AL, Ruokonen A, Sovio U, McCarthy MI, Franks S, Jarvelin MR. Body size from birth to adulthood as a predictor of self-reported polycystic ovary syndrome symptoms. Int J Obes Relat Metab Disord. 2003;27:710–715. [PubMed] 138. Sadrzadeh S, Klip WA, Broekmans FJ, Schats R, Willemsen WN, Burger CW, Van Leeuwen FE, Lambalk CB. OMEGA Project group: Birth weight and age at menarche in patients with polycystic ovary syndrome or diminished ovarian reserve, in a retrospective cohort. Hum Reprod. 2003;18:2225–2230. [PubMed] 139. McGivern RF. Low birthweight in rats induced by prenatal exposure to testosterone combined with alcohol, pair-feeding, or stress. Teratology. 1989;40:335–338. [PubMed] 140. Manikkam M, Crespi EJ, Doop DD, Herkimer C, Lee JS, Yu S, Brown MB, Foster DL, Padmanabhan V. Fetal programming: prenatal testosterone excess leads to fetal growth retardation and postnatal catch-up growth in sheep. Endocrinology. 2004;145:790–798. [PubMed] 141. Tanguy G, Thoumsin HJ, Zorn JR, Cedard L. DHEA-S-loading test in cases of intrauterine growth retardation: relationship between the pattern of the maternal plasma metabolites and the fetoplacental dysfunction. Gynecol Obstet Invest. 1981;12:305–316. [PubMed] 142. Thoumsin HJ, Alsat E, Cedard L. In vitro aromatization of androgens into estrogens in placental insufficiency. Gynecol Obstet Invest. 1982;13:37–43. [PubMed]
143. Astapova O, Steckler TS, Lee TM, Jackson LM, Padmanabhan V. Fetal programming: Advanced placentome differentiation in testosterone-treated sheep is facilitated by androgenic actions of testosterone. Abstract. 2005;579(Biol Rep Special Issue):209.
144. Crespi EJ, Steckler T, Mohankumar PS, Padmanabhan V. Prenatal testosterone excess and IGF bioavailability during intrauterine growth retardation and postnatal catch-up growth in sheep. J Physiology. 2006;572:119–130.
145. Slob AK, den Hamer R, Woutersen PJ, van der Werff ten Bosch JJ. Prenatal testosterone propionate and postnatal ovarian activity in the rat. Acta Endocrinol (Copenh) 1983;103:420–427. [PubMed] 146. Herman RA, Jones B, Mann DR, Wallen K. Timing of prenatal exposure: anatomical and endocrine effects on junvenile male and female rhesus monkeys. Horm Behav. 2000;38:52–66. [PubMed] 147. Desai M, Hales CN. Role of fetal and infant growth in programming metabolism in later life. Biol Rev. 1997;72:329–348. [PubMed] 148. Wolf CJ, LeBlanc GA, Gray LE., Jr Interactive effects of vinclozolin and testosterone propionate on pregnancy and sexual differentiation of the male and female SD rat. Toxicol Sci. 2004;78:135–143. [PubMed] 149. Moran C, Azziz R. The role of the adrenal cortex in polycystic ovary syndrome. Obstet Gynecol Clin North Am. 2001;28:63–75. [PubMed] 150. Carmina E, Koyama T, Chang L, Stanczyk FZ, Lobo RA. Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome? Am J Obstet Gynecol. 1992;167:1807–1812. [PubMed] 151. Beck Peccoz P, Padmanabhan V, Baggiani AM, Cortelazzi D, Buscaglia M, Medri G, Marconi AM, Pardi G, Beitins IZ. Maturation of hypothalamic-pituitary-gonadal function in normal human fetuses: circulating levels of gonadotropins, their common alpha-subunit and free testosterone, and discrepancy between immunological and biological activities of circulating follicle-stimulating hormone. J Clin Endocrinol Metab. 1991;73:525–532. [PubMed] 152. Yildiz BO, Yarali H, Oguz H, Bayraktar M. Glucose intolerance, insulin resistance, and hyperandrogenemia in first degree relatives of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88:2031–2036. [PubMed] 153. Fox R. Prevalence of a positive family history of type 2 diabetes in women with polycystic ovarian disease. Gynecol Endocrinol. 1999;13:390–393. [PubMed] 154. Sir-Petermann T, Angel B, Maliqueo M, Carvajal F, Santos JL, Perez-Bravo F. Prevalence of Type II diabetes mellitus and insulin resistance in parents of women with polycystic ovary syndrome. Diabetologia. 2002;45:959–964. [PubMed] 155. Bruns CM, Baum ST, Colman RJ, Eisner JR, Kemnitz JW, Weindruch R, Abbott DH. Insulin resistance and impaired insulin secretion in prenatally androgenized male rhesus monkeys. J Clin Endocrinol Metab. 2004;89:6218–6223. [PubMed] 156. Shifren JL, Osathanondh R, Yeh J. Human fetal ovaries and uteri: developmental expression of genes encoding the insulin, insulin-like growth factor I, and insulin-like growth factor II receptors. Fertil Steril. 1993;59:1036–1040. [PubMed] 157. Cole B, Hensinger K, Maciel GAR, Chang RJ, Erickson GF. Human fetal ovary development involves the spatiotemporal expression of p450c17 protein. J Clin Endocrinol Metab. 2006;91:3654–3661. [PubMed] 158. Driscoll SG, Benirschke K, Curtis GW. Neonatal deaths among infants of diabetic mothers. Postmortem findings in ninety-five infants. Am J Dis Child. 1960;100:818–835. [PubMed] 159. Hultquist GT, Olding LB. Endocrine pathology of infants of diabetic mothers. A quantitative morphological analysis including a comparison with infants of iso-immunized and of non-diabetic mothers. Acta Endocrinol (Copenh) 1981;241 Suppl:1–202. [PubMed] 160. Barbieri RL, Saltzman DH, Torday JS, Randall RW, Frigoletto FD, Ryan KJ. Elevated concentrations of the β-subunit of human chorionic gonadotropin and testosterone in the amniotic fluid of gestations of diabetic mothers. Am J Obstet Gynecol. 1986;154:1039–1043. [PubMed] 161. Senekjian EK, Potkul RK, Frey K, Herbst AL. Infertility among daughters either exposed or not exposed to diethylstilbestrol. Am J Obstet Gynecol. 1988;158:493–498. [PubMed] 162. Newbold RR. Lessons learned from perinatal exposure to diethylstilbestrol. Toxicol Appl Pharmacol. 2004;199:142–150. [PubMed]
163. Tchernitchin AN, Tchernitchin N. Imprinting of paths of heterodifferentiation by prenatal or neonatal exposure to hormone, pharmaceuticals, pollutants and other agents or conditions. Med Sci Res. 1992;20:391–397.
164. Tchernitchin AN, Tchernitchin NN, Mena MA, Unda C, Soto J. Imprinting: perinatal exposures cause the development of diseases during the adult age. Acta Biol Hung. 1999;50:425–440. [PubMed] 165. Newbold RR, Bullock BC, McLachlan JA. Exposure to diethylstilbestrol during pregnancy permanently alters the ovary and oviduct. Biol Reprod. 1983;28:735–744. [PubMed] 166. Steckler T, Manikkam M, Inskeep EK, Padmanabhan V. Developmental Programming: Follicular persistence in prenatal testosterone-treated sheep is not programmed by androgenic actions of testosterone. Endocrinology. in press [PubMed] 167. Savabieasfahani M, Kannan K, Astapova O, Evans NP, Padmanabhan V. Developmental programming: differential effects of prenatal exposure to bisphenol-A or methoxychlor on reproductive function. Endocrinology. 2006;147:5956–5966. [PubMed] 168. Zachos NC, Billiar RB, Albrecht ED, Pepe GJ. Developmental regulation of baboon fetal ovarian maturation by estrogen. Biol Reprod. 2002;67:1148–1156. [PubMed] 169. Zachos NC, Billiar RB, Albrecht ED, Pepe GJ. Regulation of oocyte microvilli development in the baboon fetal ovary by estrogen. Endocrinology. 2004;145:959–966. [PubMed] 170. Cecconi S, Ciccarelli C, Barberi M, Macchiarelli G, Canipari R. Granulosa cell-oocyte interactions. Eur J Obstet Gynecol Reprod Biol. 2004;115 Suppl 1:S19–S22. [PubMed] 171. Hautanen A, Raikkonen K, Adlercreutz H. Associations between pituitary-adrenocortical function and abdominal obesity, hyperinsulinaemia and dyslipidaemia in normotensive males. J Intern Med. 1997;241:451–461. [PubMed] 172. Rees WD, Wilson FA, Maloney CA. Sulfur amino acid metabolism in pregnancy: the impact of methionine in the maternal diet. J Nutr. 2006;136 Suppl 6:1701S–1705S. [PubMed] 173. Kwong WY, Miller DJ, Wilkins AP, Dear MS, Wright JN, Osmond C, Zhang J, Fleming TP. Maternal low protein diet restricted to the preimplantation period induces a gender-specific change on hepatic gene expression in rat fetuses. Mol Reprod Dev. 2007;74:48–56. [PubMed] 174. Park BH, Kim YJ, Park JS, Lee HY, Ha EH, Min JW, Park HS. Folate and homocysteine levels during pregnancy affect DNA methylation in human placenta. J Prev Med Pub Health. 2005;38:437–442. [PubMed]