Document Detail

Developmental programming: impact of prenatal testosterone excess on ovarian cell proliferation and apoptotic factors in sheep.
MedLine Citation:
PMID:  22539681     Owner:  NLM     Status:  MEDLINE    
Prenatal testosterone (T) excess leads to reproductive dysfunctions in sheep, which include increased ovarian follicular recruitment and persistence. To test the hypothesis that follicular disruptions in T sheep stem from changes in the developmental ontogeny of ovarian proliferation and apoptotic factors, pregnant Suffolk sheep were injected twice weekly with T propionate or dihydrotestosterone propionate (DHT; a nonaromatizable androgen) from Days 30 to 90 of gestation. Changes in developmental expression of proliferating cell nuclear antigen (PCNA), BCL2, BAX, activated CASP3, and FAS/FASLG were determined at Fetal Days 90 and 140, 22 wk, 10 mo, and 21 mo of age by immunocytochemisty. Prenatal T treatment induced changes in expression of proliferative and apoptotic markers in a follicle-, age-, and steroid-specific manner. Changes in BAX were evident only during fetal life and PCNA, BCL2, and CASP3 only postnatally. Prenatal T and not DHT increased PCNA and decreased BCL2 in granulosa/theca cells of antral follicles at 10 and 21 mo but decreased CASP3 in granulosa/theca cells of antral follicles at 22 wk (prepubertal) and 10 and 21 mo. Both treatments decreased BAX immunostaining in granulosa cells of Fetal Day 90 primordial/primary follicles. Neither treatment affected FAS expression at any developmental time point in any follicular compartment. Effects on BAX appear to be programmed by androgenic actions and PCNA, BCL2, and CASP3 by estrogenic actions of T. Overall, the findings demonstrate that fetal exposure to excess T disrupts the ovarian proliferation/apoptosis balance, thus providing a basis for the follicular disruptions evidenced in these females.
Natalia R Salvetti; Hugo H Ortega; Almudena Veiga-Lopez; Vasantha Padmanabhan
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-07-26
Journal Detail:
Title:  Biology of reproduction     Volume:  87     ISSN:  1529-7268     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-27     Completed Date:  2012-11-30     Revised Date:  2014-11-09    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  22, 1-10     Citation Subset:  IM    
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MeSH Terms
Antigens, CD95 / metabolism
Apoptosis / drug effects,  physiology
Caspase 3 / metabolism
Cell Proliferation / drug effects
Dihydrotestosterone / administration & dosage,  analogs & derivatives
Fas Ligand Protein / metabolism
Ovary / drug effects*,  pathology*,  physiopathology
Prenatal Exposure Delayed Effects / pathology*,  physiopathology
Proliferating Cell Nuclear Antigen / metabolism
Proto-Oncogene Proteins c-bcl-2 / metabolism
Testosterone Propionate / administration & dosage*
Translational Medical Research
Grant Support
Reg. No./Substance:
0/Antigens, CD95; 0/Fas Ligand Protein; 0/Proliferating Cell Nuclear Antigen; 0/Proto-Oncogene Proteins c-bcl-2; 08J2K08A3Y/Dihydrotestosterone; 855-22-1/dihydrotestosterone propionate; EC 3.4.22.-/Caspase 3; WI93Z9138A/Testosterone Propionate
Comment In:
Biol Reprod. 2012 Jul;87(1):21, 1-2   [PMID:  22553219 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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