This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Manikkam, M. Articles by Padmanabhan, V. Search for Related Content PubMed PubMed Citation Articles by Manikkam, M. Articles by Padmanabhan, V.

Fetal Programming: Prenatal Testosterone Treatment Leads to Follicular Persistence/Luteal Defects; Partial Restoration of Ovarian Function by Cyclic Progesterone Treatment

Departments of Pediatrics (M.M., V.P.) and the Reproductive Sciences Program (M.M., T.L.S., V.P.), and the Center for Statistical Consultation and Research (K.W.), University of Michigan, Ann Arbor, Michigan 48109; and Division of Animal and Veterinary Sciences, West Virginia University (E.K.I.), Morgantown, West Virginia 26506

Address all correspondence and requests for reprints to: Dr. Vasantha Padmanabhan, Department of Pediatrics and Reproductive Sciences Program, University of Michigan, 300 North Ingalls Building, Room 1109 Southwest, Ann Arbor, Michigan 48109-0404. E-mail: vasantha{at}umich.edu.

Prenatal testosterone (T) excess during midgestation leads to estrous cycle defects and polycystic ovaries in sheep. We hypothesized that follicular persistence causes polycystic ovaries and that cyclic progesterone (P) treatment would overcome follicular persistence and restore cyclicity. Twice-weekly blood samples for P measurements were taken from control (C; n = 16) and prenatally T-treated (T60; n = 14; 100 mg T, im, twice weekly from d 30–90 of gestation) Suffolk sheep starting before the onset of puberty and continuing through the second breeding season. A subset of C and T60 sheep were treated cyclically with a modified controlled internal drug-releasing device for 13–14 d every 17 d during the first anestrus (CP, 7; TP, 6). Transrectal ovarian ultrasonography was performed for 8 d in the first and 21 d in the second breeding season. Prenatal T excess reduced the number, but increased the duration of progestogenic cycles, reduced the proportion of ewes with normal cycles, increased the proportion of ewes with subluteal cycles, decreased the proportion of ewes with ovulatory cycles, induced the occurrence of persistent follicles, and reduced the number of corpora lutea in those that cycled. Cyclic P treatment in anestrus, which produced one third the P concentration seen during luteal phase of cycle, did not reduce the number of persistent follicles, but increased the number of progestogenic cycles while reducing their duration. These findings suggested that follicular persistence might contribute to the polycystic ovarian morphology. Cyclic P treatment was able to only partially restore follicular dynamics, but this may be related to the low replacement concentrations of P achieved.

This article has been cited by other articles:

				V. A Sander, G. B Facorro, L. Piehl, E. Rubin de Celis, and A. B Motta Effect of DHEA and metformin on corpus luteum in mice Reproduction, September 1, 2009; 138(3): 571 - 579. [Abstract] [Full Text] [PDF]

				L. M. Jackson, K. M. Timmer, and D. L. Foster Organizational Actions of Postnatal Estradiol in Female Sheep Treated Prenatally with Testosterone: Programming of Prepubertal Neuroendocrine Function and the Onset of Puberty Endocrinology, May 1, 2009; 150(5): 2317 - 2324. [Abstract] [Full Text] [PDF]

				H. H Ortega, N. R Salvetti, and V. Padmanabhan Developmental programming: prenatal androgen excess disrupts ovarian steroid receptor balance Reproduction, May 1, 2009; 137(5): 865 - 877. [Abstract] [Full Text] [PDF]

				P. Smith, T. L. Steckler, A. Veiga-Lopez, and V. Padmanabhan Developmental Programming: Differential Effects of Prenatal Testosterone and Dihydrotestosterone on Follicular Recruitment, Depletion of Follicular Reserve, and Ovarian Morphology in Sheep Biol Reprod, April 1, 2009; 80(4): 726 - 736. [Abstract] [Full Text] [PDF]

				A. Veiga-Lopez, O. I. Astapova, E. F. Aizenberg, J. S. Lee, and V. Padmanabhan Developmental Programming: Contribution of Prenatal Androgen and Estrogen to Estradiol Feedback Systems and Periovulatory Hormonal Dynamics in Sheep Biol Reprod, April 1, 2009; 80(4): 718 - 725. [Abstract] [Full Text] [PDF]

				T. L. Steckler, C. Herkimer, D. A. Dumesic, and V. Padmanabhan Developmental Programming: Excess Weight Gain Amplifies the Effects of Prenatal Testosterone Excess On Reproductive Cyclicity--Implication for Polycystic Ovary Syndrome Endocrinology, March 1, 2009; 150(3): 1456 - 1465. [Abstract] [Full Text] [PDF]

				S. E. Recabarren, P. P. Rojas-Garcia, M. P. Recabarren, V. H. Alfaro, R. Smith, V. Padmanabhan, and T. Sir-Petermann Prenatal Testosterone Excess Reduces Sperm Count and Motility Endocrinology, December 1, 2008; 149(12): 6444 - 6448. [Abstract] [Full Text] [PDF]

				T. L. Steckler, J. S. Lee, W. Ye, E. K. Inskeep, and V. Padmanabhan Developmental Programming: Exogenous Gonadotropin Treatment Rescues Ovulatory Function But Does Not Completely Normalize Ovarian Function in Sheep Treated Prenatally with Testosterone Biol Reprod, October 1, 2008; 79(4): 686 - 695. [Abstract] [Full Text] [PDF]

				R. Sotomayor-Zarate, M. Dorfman, A. Paredes, and H. E. Lara Neonatal Exposure to Estradiol Valerate Programs Ovarian Sympathetic Innervation and Follicular Development in the Adult Rat Biol Reprod, April 1, 2008; 78(4): 673 - 680. [Abstract] [Full Text] [PDF]

				M. Manikkam, R. C. Thompson, C. Herkimer, K. B. Welch, J. Flak, F. J. Karsch, and V. Padmanabhan Developmental Programming: Impact of Prenatal Testosterone Excess on Pre- and Postnatal Gonadotropin Regulation in Sheep Biol Reprod, April 1, 2008; 78(4): 648 - 660. [Abstract] [Full Text] [PDF]

				A. Veiga-Lopez, W. Ye, D.J. Phillips, C. Herkimer, P.G. Knight, and V. Padmanabhan Developmental Programming: Deficits in Reproductive Hormone Dynamics and Ovulatory Outcomes in Prenatal, Testosterone-Treated Sheep Biol Reprod, April 1, 2008; 78(4): 636 - 647. [Abstract] [Full Text] [PDF]

				L. Manneras, S. Cajander, A. Holmang, Z. Seleskovic, T. Lystig, M. Lonn, and E. Stener-Victorin A New Rat Model Exhibiting Both Ovarian and Metabolic Characteristics of Polycystic Ovary Syndrome Endocrinology, August 1, 2007; 148(8): 3781 - 3791. [Abstract] [Full Text] [PDF]

				T. Steckler, M. Manikkam, E. K. Inskeep, and V. Padmanabhan Developmental Programming: Follicular Persistence in Prenatal Testosterone-Treated Sheep Is Not Programmed by Androgenic Actions of Testosterone Endocrinology, July 1, 2007; 148(7): 3532 - 3540. [Abstract] [Full Text] [PDF]

				A. J. King, N. Bari Olivier, P. S. Mohankumar, J. S. Lee, V. Padmanabhan, and G. D. Fink Hypertension caused by prenatal testosterone excess in female sheep Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1837 - E1841. [Abstract] [Full Text] [PDF]

				M. Savabieasfahani, K. Kannan, O. Astapova, N. P. Evans, and V. Padmanabhan Developmental Programming: Differential Effects of Prenatal Exposure to Bisphenol-A or Methoxychlor on Reproductive Function Endocrinology, December 1, 2006; 147(12): 5956 - 5966. [Abstract] [Full Text] [PDF]