Developmental origin of reproductive and metabolic dysfunctions: Androgenic versus estrogenic reprogramming

Seminars in Reproductive Medicine

Volumn 29, Issue 3, 2011, Pages 173-186

  Padmanabhan, Vasantha ^a   Veiga Lopez, Almudena ^a  

^a UNIVERSITY OF MICHIGAN   (United States)

Author keywords

androgens; estrogens; fetal programming; Infertility; PCOS

Indexed keywords

ANDROGEN; ESTROGEN; FATTY ACID; GONADORELIN; INSULIN; LUTEINIZING HORMONE; PROGESTERONE;

ANDROGENIC PROGRAMMING; ANOVULATION; ARTICLE; ATHEROGENESIS; BODY FAT; CHOLESTEROL BLOOD LEVEL; DISEASE MODEL; DISEASE SEVERITY; ENVIRONMENTAL FACTOR; ESTROGENIC PROGRAMMING; FEMALE INFERTILITY; FETUS DEVELOPMENT; GENETIC ASSOCIATION; HUMAN; HYPERANDROGENISM; HYPERTENSION; INTRAUTERINE GROWTH RETARDATION; METABOLIC DISORDER; NEUROENDOCRINE SYSTEM; NONHUMAN; ORGAN WEIGHT; OVARY FOLLICLE; OVARY POLYCYSTIC DISEASE; PANCREAS ISLET BETA CELL; PERINATAL PERIOD; PHENOTYPE; POSTNATAL DEVELOPMENT; PRENATAL DEVELOPMENT; TRIACYLGLYCEROL BLOOD LEVEL; VISCERA;

ADULT; ANDROGENS; ANIMALS; ANIMALS, NEWBORN; DISEASE MODELS, ANIMAL; DISEASE SUSCEPTIBILITY; ESTROGENS; FEMALE; FETAL DEVELOPMENT; HUMANS; HYPERINSULINISM; INFERTILITY; MALE; METABOLIC DISEASES; POLYCYSTIC OVARY SYNDROME; PREGNANCY; PRENATAL EXPOSURE DELAYED EFFECTS;

EID: 79959800774     PISSN: 15268004     EISSN: 15264564     Source Type: Journal    
DOI: 10.1055/s-0031-1275519     Document Type: Article

References (116)

1. Boivin J, Bunting L, Collins J A., Nygren K G. International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care. Hum Reprod 2007 22 6 1506-1512 (Pubitemid 47055136)
2. Homburg R. Polycystic ovary syndrome: induction of ovulation. Baillieres Clin Endocrinol Metab 1996 10 2 281-292 (Pubitemid 26166056)
3. Messinis I E. Ovulation induction: a mini review. Hum Reprod 2005 20 10 2688-2697 (Pubitemid 41487621)
4. Hamilton-Fairley D, Franks S. Common problems in induction of ovulation. Baillieres Clin Obstet Gynaecol 1990 4 3 609-625
5. Tummon I, Gavrilova-Jordan L, Allemand M C., Session D. Polycystic ovaries and ovarian hyperstimulation syndrome: a systematic review. Acta Obstet Gynecol Scand 2005 84 7 611-616 (Pubitemid 40917381)
6. Boomsma C M., Fauser B C., Macklon N S. Pregnancy complications in women with polycystic ovary syndrome. Semin Reprod Med 2008 26 1 72-84
7. Janssen O E., Hahn S, Tan S, Benson S, Elsenbruch S. Mood and sexual function in polycystic ovary syndrome. Semin Reprod Med 2008 26 1 45-52
8. Himelein M J., Thatcher S S. Polycystic ovary syndrome and mental health: a review. Obstet Gynecol Surv 2006 61 11 723-732 (Pubitemid 44655530)
9. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997 18 6 774-800 (Pubitemid 28009567)
10. Lord J M., Flight I H., Norman R J. Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol) for polycystic ovary syndrome. Cochrane Database Syst Rev 2003 3 3 CD003053
11. Essah P A., Nestler J E. The metabolic syndrome in polycystic ovary syndrome. J Endocrinol Invest 2006 29 3 270-280
12. Barber T M., McCarthy M I., Wass J A., Franks S. Obesity and polycystic ovary syndrome. Clin Endocrinol (Oxf) 2006 65 2 137-145 (Pubitemid 44079674)
13. Hoffman L K., Ehrmann D A. Cardiometabolic features of polycystic ovary syndrome. Nat Clin Pract Endocrinol Metab 2008 4 4 215-222 (Pubitemid 351430905)
14. Navaratnarajah R, Pillay O C., Hardiman P. Polycystic ovary syndrome and endometrial cancer. Semin Reprod Med 2008 26 1 62-71
15. Barker D JP. Programming the baby. In: Gillman M W. Barker D JP eds. Mothers, Babies, and Disease in Later Life. London, United Kingdom BMJ Publishing Group 1994 14-36
16. Dumesic D A., Abbott D H., Padmanabhan V. Polycystic ovary syndrome and its developmental origins. Rev Endocr Metab Disord 2007 8 2 127-141 (Pubitemid 47434646)
17. Davies M J., Norman R J. Programming and reproductive functioning. Trends Endocrinol Metab 2002 13 9 386-392 (Pubitemid 36723591)
18. Barnes R B., Rosenfield R L., Ehrmann D A. et al. 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 5 1328-1333 (Pubitemid 24369843)
19. Abbott D H., Dumesic D A., Levine J E., Dunaif A, Padmanabhan V. Animal models and fetal programming of PCOS. In: Azziz R Nestler J E. Dewailly D eds. Contemporary Endocrinology: Androgen Excess Disorders in Women: Polycystic Ovary Syndrome and Other Disorders. Totowa, NJ Humana Press 2006 259-272
20. Rosenfield R L. Current concepts of polycystic ovary syndrome. Baillieres Clin Obstet Gynaecol 1997 11 2 307-333 (Pubitemid 27353118)
21. Rebar R, Judd H L., Yen S S., Rakoff J, Vandenberg G, Naftolin F. Characterization of the inappropriate gonadotropin secretion in polycystic ovary syndrome. J Clin Invest 1976 57 5 1320-1329
22. Franks S, Roberts R, Hardy K. Gonadotrophin regimens and oocyte quality in women with polycystic ovaries. Reprod Biomed Online 2003 6 2 181-184 (Pubitemid 36857146)
23. Webber L J., Stubbs S, Stark J et al. Formation and early development of follicles in the polycystic ovary. Lancet 2003 362 9389 1017-1021 (Pubitemid 37186878)
24. Foong S C., Abbott D H., Zschunke M A., Lesnick T G., Phy J L., Dumesic D A. Follicle luteinization in hyperandrogenic follicles of polycystic ovary syndrome patients undergoing gonadotropin therapy for in vitro fertilization. J Clin Endocrinol Metab 2006 91 6 2327-2333 (Pubitemid 43855024)
25. Pastor C L., Griffin-Korf M L., Aloi J A., Evans W S., Marshall J C. 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 2 582-590 (Pubitemid 28496543)
26. Patel K, Coffler M S., Dahan M H., Malcom P J., Deutsch R, Chang R J. Relationship of GnRH-stimulated LH release to episodic LH secretion and baseline endocrine-metabolic measures in women with polycystic ovary syndrome. Clin Endocrinol (Oxf) 2004 60 1 67-74 (Pubitemid 38183500)
27. Ehrmann D A. -cell dysfunction, glucose intolerance, and diabetes in the polycystic syndrome. In: Azziz R Nestler J E. Dewailly D eds. Androgen Excess Disorders in Women. Totowa, NJ Humana Press 2007 319-324
28. Ibáñez L, Potau N, Francois I, de Zegher F. Precocious pubarche, hyperinsulinism, and ovarian hyperandrogenism in girls: relation to reduced fetal growth. J Clin Endocrinol Metab 1998 83 10 3558-3562 (Pubitemid 28500889)
29. de Zegher F, Ibáñez L. Prenatal growth restraint followed by catch-up of weight: a hyperinsulinemic pathway to polycystic ovary syndrome. Fertil Steril 2006 86 Suppl 1 S4-S5
30. Diamanti-Kandarakis E. Role of obesity and adiposity in polycystic ovary syndrome. Int J Obes (Lond) 2007 31 Suppl 2 S8-S13; discussion S31S32 (Pubitemid 350023168)
31. Pasquali R, Gambineri A. The endocrine impact of obesity and body habitus in the polycystic syndrome. In: Azziz R Nestler J E. Dewailly D eds. Androgen Excess Disorders in Women. Totowa, NJ Humana Press 2007 283-291
32. Essah P A., Nestler J E. The metabolic syndrome in polycystic ovary syndrome. J Endocrinol Invest 2006 29 3 270-280
33. Eisner J R., Barnett M A., Dumesic D A., Abbott D H. Ovarian hyperandrogenism in adult female rhesus monkeys exposed to prenatal androgen excess. Fertil Steril 2002 77 1 167-172 (Pubitemid 34093911)
34. Abbott D H., Barnett D K., Bruns C M., Dumesic D A. Androgen excess fetal programming of female reproduction: a developmental aetiology for polycystic ovary syndrome? Hum Reprod Update 2005 11 4 357-374 (Pubitemid 40895465)
35. Dumesic D A., Abbott D H., Eisner J R., Goy R W. Prenatal exposure of female rhesus monkeys to testosterone propionate increases serum luteinizing hormone levels in adulthood. Fertil Steril 1997 67 1 155-163 (Pubitemid 26428430)
36. Goy R W., Robinson J A. Prenatal exposure of rhesus monkeys to patent androgens: morphological, behavioral, and physiological consequences. Banbury Rep 1982 11 355-378
37. Abbott D H., Dumesic D A., Eisner J R., Kemnitz J W., Goy R W. The prenatally androgenized female rhesus monkey as a model for polycystic ovarian syndrome. In: Azziz R Nestler J E. Dewailly D eds. Androgen Excess Disorders in Women. Philadelphia, PA Lippincott-Raven Press 1997 369-382
38. Abbott D H., Eisner J R., Colman R J., Kemnitz J, Dumesic D A. Prenatal androgen excess programs for PCOS in female rhesus monkeys. In: Chang R J. Dunaif A Hiendel J eds. Polycystic Ovary Syndrome. New York, NY Marcel Dekker 2002 119-133
39. Dumesic D A., Schramm R D., Peterson E, Paprocki A M., Zhou R, Abbott D H. 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 3 1111-1119 (Pubitemid 36121075)
40. Steiner R A., Clifton D K., Spies H G., Resko J A. Sexual differentiation and feedback control of luteinizing hormone secretion in the rhesus monkey. Biol Reprod 1976 15 2 206-212
41. Levine J E., Terasawa E, Hoffman S M., Dobbert M JW, Foecking E M., Abbott D H. Luteinizing hormone (LH) hypersecretion and diminished LH responses to RU486 in a non human primate model for polycystic ovary syndrome (PCOS). Paper presented at: Annual Meeting of the Endocrine Society; June 4, 2005; San Diego, CA
42. Eisner J R., Dumesic D A., Kemnitz J W., Abbott D H. Timing of prenatal androgen excess determines differential impairment in insulin secretion and action in adult female rhesus monkeys. J Clin Endocrinol Metab 2000 85 3 1206-1210 (Pubitemid 32269373)
43. Abbott D H., Bruns C M., Barnett D K. et al. Metabolic and reproductive consequences of prenatal testosterone exposure. Paper presented at: Annual Meeting of the Endocrine Society; June 19, 2003; Philadelphia, PA
44. Abbott D H., Barnett D K., Levine J E. et al. Endocrine antecedents of polycystic ovary syndrome in fetal and infant prenatally androgenized female rhesus monkeys. Biol Reprod 2008 79 1 154-163 (Pubitemid 351931028)
45. Eisner J R., Dumesic D A., Kemnitz J W., Colman R J., Abbott D H. Increased adiposity in female rhesus monkeys exposed to androgen excess during early gestation. Obes Res 2003 11 2 279-286 (Pubitemid 41127397)
46. Abbott D H., Eisner J R., Goodfriend T L. et al. Leptin and total free fatty acids are elevated in the circulation of prenatally androgenized female rhesus monkeys. Paper presented at: Annual Meeting of the Endocrine Society; June 18, 2002; San Francisco, CA
47. Ortega H H., Salvetti N R., Padmanabhan V. Developmental programming: prenatal androgen excess disrupts ovarian steroid receptor balance. Reproduction 2009 137 5 865-877
48. Manikkam M, Thompson R C., Herkimer C et al. Developmental programming: impact of prenatal testosterone excess on pre- and postnatal gonadotropin regulation in sheep. Biol Reprod 2008 78 4 648-660 (Pubitemid 351469344)
49. Sharma T P., Herkimer C, West C et al. Fetal programming: prenatal androgen disrupts positive feedback actions of estradiol but does not affect timing of puberty in female sheep. Biol Reprod 2002 66 4 924-933 (Pubitemid 34263111)
50. Sarma H N., Manikkam M, Herkimer C, Dell'Orco J, Foster D L., Padmanabhan V. Fetal programming: excess prenatal testosterone reduces postnatal LH, but not FSH responsiveness to estradiol negative feedback in the female. Endocrinology 2005 146 4281-4291 (Pubitemid 41324024)
51. Birch R A., Padmanabhan V, Foster D L., Unsworth W P., Robinson J E. Prenatal programming of reproductive neuroendocrine function: fetal androgen exposure produces progressive disruption of reproductive cycles in sheep. Endocrinology 2003 144 4 1426-1434 (Pubitemid 36428485)
52. Manikkam M, Steckler T L., Welch K B., Inskeep E K., 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 4 1997-2007
53. Steckler T, Manikkam M, Inskeep E K., Padmanabhan V. Developmental programming: follicular persistence in prenatal testosterone-treated sheep is not programmed by androgenic actions of testosterone. Endocrinology 2007 148 7 3532-3540 (Pubitemid 46997017)
54. Manikkam M, Crespi E J., Doop D D. et al. Fetal programming: prenatal testosterone excess leads to fetal growth retardation and postnatal catch-up growth in sheep. Endocrinology 2004 145 2 790-798 (Pubitemid 38183822)
55. Steckler T L., Roberts E K., Doop D D., Lee T M., Padmanabhan V. Developmental programming in sheep: administration of testosterone during 60-90 days of pregnancy reduces breeding success and pregnancy outcome. Theriogenology 2007 67 3 459-467 (Pubitemid 46026847)
56. West C, Foster D L., Evans N P., Robinson J, Padmanabhan V. Intra-follicular activin availability is altered in prenatally-androgenized lambs. Mol Cell Endocrinol 2001 185 12 51-59 (Pubitemid 33103953)
57. Smith P, Steckler T L., Veiga-Lopez A, Padmanabhan V. Developmental programming: differential effects of prenatal testosterone and dihydrotestosterone on follicular recruitment, depletion of follicular reserve, and ovarian morphology in sheep. Biol Reprod 2009 80 4 726-736
58. Forsdike R A., Hardy K, Bull L et al. Disordered follicle development in ovaries of prenatally androgenized ewes. J Endocrinol 2007 192 2 421-428 (Pubitemid 46444443)
59. Steckler T, Wang J, Bartol F F., Roy S K., Padmanabhan V. Fetal programming: prenatal testosterone treatment causes intrauterine growth retardation, reduces ovarian reserve and increases ovarian follicular recruitment. Endocrinology 2005 146 7 3185-3193 (Pubitemid 41007051)
60. Unsworth W P., Taylor J A., Robinson J E. 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 3 619-627 (Pubitemid 40279840)
61. Robinson J E., Forsdike R A., Taylor J A. 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 12 5797-5805 (Pubitemid 30645369)
62. Veiga-Lopez A, Ye W, Phillips D J., Herkimer C, Knight P G., Padmanabhan V. Developmental programming: deficits in reproductive hormone dynamics and ovulatory outcomes in prenatal, testosterone-treated sheep. Biol Reprod 2008 78 4 636-647 (Pubitemid 351469343)
63. Recabarren S E., Padmanabhan V, Codner E et al. Postnatal developmental consequences of altered insulin sensitivity in female sheep treated prenatally with testosterone. Am J Physiol Endocrinol Metab 2005 289 5 E801-E806 (Pubitemid 41504379)
64. Padmanabhan V, Veiga-Lopez A, Abbott D H., Recabarren S E., Herkimer C. Developmental programming: impact of prenatal testosterone excess and postnatal weight gain on insulin sensitivity index and transfer of traits to offspring of overweight females. Endocrinology 2010 151 2 595-605
65. King A J., Olivier N B., Mohankumar P S., Lee J S., Padmanabhan V, Fink G D. Hypertension caused by prenatal testosterone excess in female sheep. Am J Physiol Endocrinol Metab 2007 292 6 E1837-E1841 (Pubitemid 47084721)
66. Foecking E M., Szabo M, Schwartz N B., Levine J E. 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 6 1475-1483 (Pubitemid 40696090)
67. Wu X Y., Li Z L., Wu C Y. et al. Endocrine traits of polycystic ovary syndrome in prenatally androgenized female Sprague-Dawley rats. Endocr J 2010 57 3 201-209
68. Demissie M, Lazic M, Foecking E M., Aird F, Dunaif A, Levine J E. Transient prenatal androgen exposure produces metabolic syndrome in adult female rats. Am J Physiol Endocrinol Metab 2008 295 2 E262-E268
69. Slob A K., den Hamer R, Woutersen P J., van der Werff ten Bosch J J. Prenatal testosterone propionate and postnatal ovarian activity in the rat. Acta Endocrinol (Copenh) 1983 103 3 420-427 (Pubitemid 13060447)
70. Alexanderson C, Eriksson E, Stener-Victorin E et al. Postnatal testosterone exposure results in insulin resistance, enlarged mesenteric adipocytes, and an atherogenic lipid profile in adult female rats: comparisons with estradiol and dihydrotestosterone. Endocrinology 2007 148 11 5369-5376 (Pubitemid 350012629)
71. Nilsson C, Niklasson M, Eriksson E, Björntorp P, Holmäng A. Imprinting of female offspring with testosterone results in insulin resistance and changes in body fat distribution at adult age in rats. J Clin Invest 1998 101 1 74-78 (Pubitemid 28058905)
72. Cheng G, Coolen L M., Padmanabhan V, Goodman R L., Lehman M N. The kisspeptin/neurokinin B/dynorphin (KNDy) cell population of the arcuate nucleus: sex differences and effects of prenatal testosterone in sheep. Endocrinology 2010 151 1 301-311
73. Padmanabhan V, Veiga-Lopez A, Abbott D H., Dumesic D A. Developmental programming of ovarian dysfunction. In: Gonzalez-Bulnes A ed. Novel Concepts in Ovarian Endocrinology. Kerala, India Research Signpost Editors 2007 328-352
74. Kennedy T G., Gillio-Meina C, Phang S H. Prostaglandins and the initiation of blastocyst implantation and decidualization. Reproduction 2007 134 5 635-643 (Pubitemid 350143146)
75. Pelliniemi L J., Fröjdman K. Structural and regulatory macromolecules in sex differentiation of gonads. J Exp Zool 2001 290 5 523-528 (Pubitemid 32930902)
76. Hemsworth B N., Jackson H. Effect of busulphan on the developing ovary in the rat. J Reprod Fertil 1963 6 229-233
77. Rajah R, Glaser E M., Hirshfield A N. The changing architecture of the neonatal rat ovary during histogenesis. Dev Dyn 1992 194 3 177-192
78. Malamed S, Gibney J A., Ojeda S R. Ovarian innervation develops before initiation of folliculogenesis in the rat. Cell Tissue Res 1992 270 1 87-93
79. Ortega H H., Rey F, Velazquez M M., Padmanabhan V. Developmental programming: effect of prenatal steroid excess on intraovarian components of insulin signaling pathway and related proteins in sheep. Biol Reprod 2010 82 6 1065-1075
80. Welt C K., Taylor A E., Fox J, Messerlian G M., Adams J M., Schneyer A L. Follicular arrest in polycystic ovary syndrome is associated with deficient inhibin A and B biosynthesis. J Clin Endocrinol Metab 2005 90 10 5582-5587 (Pubitemid 41415462)
81. Fujiwara T, Sidis Y, Welt C et al. Dynamics of inhibin subunit and follistatin mRNA during development of normal and polycystic ovary syndrome follicles. J Clin Endocrinol Metab 2001 86 9 4206-4215 (Pubitemid 32848537)
82. Brown E, Lee T, Padmanabhan V, Lehman M N., Coolen L M. The ventral tegmental area dopamine system is masculinized by prenatal testosterone via androgen receptor action in female sheep. Paper presented at: Annual Meeting of Society for Behavioral Neuroendocrinology; July 18, 2010; Toronto, ON, Canada
83. Fauser B C., Diedrich K, Devroey P, Evian Annual Reproduction Workshop Group 2007. Predictors of ovarian response: progress towards individualized treatment in ovulation induction and ovarian stimulation. Hum Reprod Update 2008 14 1 1-14
84. Zawadki J K., Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A Givens J R. Haseltine F P. Merriam G R. eds. Polycystic Ovary Syndrome. Boston, MA Blackwell Scientific 1992 377-384
85. 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 1 41-47
86. Azziz R, Carmina E, Dewailly D et al, Androgen Excess Society. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab 2006 91 11 4237-4245 (Pubitemid 44833391)
87. Wild R A., Carmina E, Diamanti-Kandarakis E et al. Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society. J Clin Endocrinol Metab 2010 95 5 2038-2049
88. Veiga-Lopez A, Astapova O I., Aizenberg E F., Lee J S., Padmanabhan V. Developmental programming: contribution of prenatal androgen and estrogen to estradiol feedback systems and periovulatory hormonal dynamics in sheep. Biol Reprod 2009 80 4 718-725
89. Sullivan S D., Moenter S M. Prenatal androgens alter GABAergic drive to gonadotropin-releasing hormone neurons: implications for a common fertility disorder. Proc Natl Acad Sci U S A 2004 101 18 7129-7134 (Pubitemid 38596454)
90. Roland A V., Nunemaker C S., Keller S R., Moenter S M. Prenatal androgen exposure programs metabolic dysfunction in female mice. J Endocrinol 2010 207 2 213-223
91. Mannerås L, Cajander S, Holmäng A et al. A new rat model exhibiting both ovarian and metabolic characteristics of polycystic ovary syndrome. Endocrinology 2007 148 8 3781-3791 (Pubitemid 47105840)
92. 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 2 103-108 (Pubitemid 38316828)
93. Baravalle C, Salvetti N R., Mira G A., Pezzone N, Ortega H H. Microscopic characterization of follicular structures in letrozole-induced polycystic ovarian syndrome in the rat. Arch Med Res 2006 37 7 830-839 (Pubitemid 44349101)
94. Rosa-E-Silva A, Guimaraes M A., Padmanabhan V, Lara H E. Prepubertal administration of estradiol valerate disrupts cyclicity and leads to cystic ovarian morphology during adult life in the rat: role of sympathetic innervation. Endocrinology 2003 144 10 4289-4297 (Pubitemid 37204827)
95. Handa R J., Pak T R., Kudwa A E., Lund T D., Hinds L. An alternate pathway for androgen regulation of brain function: activation of estrogen receptor beta by the metabolite of dihydrotestosterone, 5alpha-androstane-3beta, 17beta-diol. Horm Behav 2008 53 5 741-752
96. Sotomayor-Zárate R, Dorfman M, Paredes A, Lara H E. Neonatal exposure to estradiol valerate programs ovarian sympathetic innervation and follicular development in the adult rat. Biol Reprod 2008 78 4 673-680 (Pubitemid 351469346)
97. Veiga-Lopez A, Steckler T L., Abbott D H. et al. Developmental programming: impact of excess prenatal testosterone on intra-uterine fetal endocrine milieu and growth in sheep. Biol Reprod 2011 84 1 87-96
98. Wood R I., Foster D L. Sexual differentiation of reproductive neuroendocrine function in sheep. Rev Reprod 1998 3 2 130-140 (Pubitemid 28310285)
99. Foster D L., Padmanabhan V, Wood R I., Robinson J E. Sexual differentiation of the neuroendocrine control of gonadotrophin secretion: concepts derived from sheep models. Reprod Suppl 2002 59 83-99
100. Steckler T L., Herkimer C, Dumesic D A., Padmanabhan V. Developmental programming: excess weight gain amplifies the effects of prenatal testosterone excess on reproductive cyclicityimplication for polycystic ovary syndrome. Endocrinology 2009 150 3 1456-1465
101. Ludwig D S. Childhood obesitythe shape of things to come. N Engl J Med 2007 357 23 2325-2327 (Pubitemid 350223386)
102. Moran L J., Brinkworth G D., Norman R J. Dietary therapy in polycystic ovary syndrome. Semin Reprod Med 2008 26 1 85-92
103. Tang T, Lord J M., Norman R J., Yasmin E, Balen A H. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev 2010 1 CD003053
104. Veiga-Lopez A, Lee J S., Padmanabhan V. Developmental programming: insulin sensitizer treatment improves reproductive function in prenatal testosterone-treated female sheep. Endocrinology 2010 151 8 4007-4017
105. Zhou R, Bruns C M., Bird I M. et al. Pioglitazone improves insulin action and normalizes menstrual cycles in a majority of prenatally androgenized female rhesus monkeys. Reprod Toxicol 2007 23 3 438-448 (Pubitemid 46602932)
106. Dasgupta S, Reddy B M. Present status of understanding on the genetic etiology of polycystic ovary syndrome. J Postgrad Med 2008 54 2 115-125 (Pubitemid 351724195)
107. Yildiz B O., 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 5 2031-2036 (Pubitemid 36549872)
108. Vink J M., Sadrzadeh S, Lambalk C B., Boomsma D I. Heritability of polycystic ovary syndrome in a Dutch twin-family study. J Clin Endocrinol Metab 2006 91 6 2100-2104 (Pubitemid 43854989)
109. Waterland R A. Is epigenetics an important link between early life events and adult disease? Horm Res 2009 71 Suppl 1 13-16
110. Hickey T E., Legro R S., Norman R J. Epigenetic modification of the X chromosome influences susceptibility to polycystic ovary syndrome. J Clin Endocrinol Metab 2006 91 7 2789-2791 (Pubitemid 44024652)
111. Gemzell-Danielsson K, Marions L. Mechanisms of action of mifepristone and levonorgestrel when used for emergency contraception. Hum Reprod Update 2004 10 4 341-348 (Pubitemid 38997071)
112. Kasa-Vubu J Z., Dahl G E., Evans N P. et al. Progesterone blocks the estradiol-induced gonadotropin discharge in the ewe by inhibiting the surge of gonadotropin-releasing hormone. Endocrinology 1992 131 1 208-212
113. Levine J E. New concepts of the neuroendocrine regulation of gonadotropin surges in rats. Biol Reprod 1997 56 2 293-302 (Pubitemid 27081569)
114. Beck-Peccoz P, Padmanabhan V, Baggiani A M. et al. 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 3 525-532 (Pubitemid 21921904)
115. Diamanti-Kandarakis E, Bourguignon J P., Giudice L C. et al. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr Rev 2009 30 4 293-342
116. Sir-Petermann T, Codner E, Pérez V et al. Metabolic and reproductive features before and during puberty in daughters of women with polycystic ovary syndrome. J Clin Endocrinol Metab 2009 94 6 1923-1930