Document Detail

Effects of neonatal progestin exposure on female reproductive tract structure and function in the adult ewe.
MedLine Citation:
PMID:  11207194     Owner:  NLM     Status:  MEDLINE    
Endometrial glands are present in all mammalian uteri and produce secretions that are hypothesized to support conceptus (i.e., embryo/fetus and placental membranes) survival and development. In sheep, endometrial gland morphogenesis occurs postnatally and can be epigenetically ablated by chronic neonatal exposure to a progestin from birth, thereby producing an adult uterine gland knock-out (UGKO) phenotype. This study determined the long-term effects of neonatal progestin exposure on adult ovine reproductive tract structure and function. Neonatal ewes were exposed to norgestomet (Nor) from birth to 32 wk of age. Unexposed ewes served as controls. After puberty, adult Nor-treated (n = 6) and control (n = 6) ewes were repeatedly bred at estrus (Day 0) to intact rams of proven fertility. In contrast to a pregnancy rate of 80% for control ewes, pregnancy was never detected on Day 25 after mating (or thereafter) in bred UGKO ewes. Control and Nor-treated ewes were then bred and necropsied on Day 9. Similar numbers of hatched blastocysts were present in uterine flushings from control and Nor-treated ewes. Weights of the ovaries and cervices were not affected by treatment. No histoarchitectural differences between control and Nor-treated ewes were detected for ovaries, oviducts, cervices, or vaginae. However, uterocervical and uterine weight as well as uterine horn length were less for Nor-treated ewes. The uteri of Nor-treated ewes were devoid of endometrial glands and lacked the stromal delineation characteristic of intercaruncular endometrium in control ewes. Endometrial width, area, and lumenal epithelial length were decreased in uteri from Nor-treated ewes, but myometrial width and morphology were not affected. Expression of a number of mRNAs that are expressed predominantly in the endometrial epithelia was not different between uteri from control and from Nor-treated ewes. Collectively, these results indicate that neonatal exposure of ewes to a progestin from birth appears to only affect development of the uterus and not any extrauterine reproductive tract tissues. The infertility of the UGKO ewes appears to result from a lack of endometrial glands and, by extension, of their secretions that are required to support growth and development of peri-implantation conceptuses.
C A Gray; F W Bazer; T E Spencer
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biology of reproduction     Volume:  64     ISSN:  0006-3363     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2001 Mar 
Date Detail:
Created Date:  2001-03-14     Completed Date:  2001-05-31     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  797-804     Citation Subset:  IM    
Center for Animal Biotechnology and Genomics and the Department of Animal Science, Texas A&M University, College Station, Texas 77843-2471, USA.
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MeSH Terms
Animals, Newborn
Fertility / drug effects
Genitalia, Female / anatomy & histology,  drug effects*,  physiology
Image Processing, Computer-Assisted
In Situ Hybridization
Least-Squares Analysis
Pregnenediones / pharmacology*
Progesterone Congeners / pharmacology*
Random Allocation
Sheep / growth & development*
Uterus / anatomy & histology,  drug effects,  physiology
Grant Support
Reg. No./Substance:
0/Pregnenediones; 0/Progesterone Congeners; 25092-41-5/norgestomet

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

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