Document Detail

Ovine uterine gland knock-out model: effects of gland ablation on the estrous cycle.
MedLine Citation:
PMID:  10642586     Owner:  NLM     Status:  MEDLINE    
Ovine endometrial gland development is a postnatal event that can be inhibited epigenetically by chronic exposure of ewe lambs to a synthetic progestin from birth to puberty. As adults, these neonatally progestin-treated ewes lack endometrial glands and display a uterine gland knockout (UGKO) phenotype that is useful as a model for study of endometrial function. Here, objectives were to determine: 1) length of progestin exposure necessary from birth to produce the UGKO phenotype in ewes; 2) if UGKO ewes display normal estrous cycles; and 3) if UGKO ewes could establish and/or maintain pregnancy. Ewe lambs (n = 22) received a Norgestomet (Nor) implant at birth and every two weeks thereafter for 8 (Group I), 16 (Group II), or 32 (Groups III and IV) weeks. Control ewe lambs (n = 13) received no Nor treatment (Groups V and VI). Ewes in Groups I, II, III, and VI were hemihysterectomized (Hhx) at 16 weeks of age. After puberty, the remaining uterine horn in Hhx ewes was removed on either Day 9 or 15 of the estrous cycle (Day 0 = estrus). Histological analyses of uteri indicated that progestin exposure for 8, 16, or 32 weeks prevented endometrial adenogenesis and produced the UGKO phenotype in adult ewes. Three endometrial phenotypes were consistently observed in Nor-treated ewes: 1) no glands, 2) slight glandular invaginations into the stroma, and 3) limited numbers of cyst- or gland-like structures in the stroma. Overall patterns of uterine progesterone, estrogen, and oxytocin receptor expression were not different in uteri from adult cyclic control and UGKO ewes. However, receptor expression was variegated in the ruffled luminal epithelium of uteri from UGKO ewes. Intact UGKO ewes displayed altered estrous cycles with interestrous intervals of 17 to 43 days, and they responded to exogenous prostaglandin F(2 approximately ) (PGF) with luteolysis and behavioral estrus. During the estrous cycle, plasma concentrations of progesterone in intact control and UGKO ewes were not different during metestrus and diestrus, but levels did not decline in many UGKO ewes during late diestrus. Peak peripheral plasma concentrations of PGF metabolite, in response to an oxytocin challenge on Day 15, were threefold lower in UGKO compared to control ewes. Intact UGKO ewes bred repeatedly to intact rams did not display evidence of pregnancy based on results of ultrasound. Collectively, results indicate that 1) transient, progestin-induced disruption of ovine uterine development from birth alters both structural and functional integrity of the adult endometrium; 2) normal adult endometrial integrity, including uterine glands, is required to insure a luteolytic pattern of PGF production; and 3) the UGKO phenotype, characterized by the absence of endometrial glands and a compact, disorganized endometrial stroma, limits or inhibits the capacity of uterine tissues to support the establishment and/or maintenance of pregnancy.
C Allison Gray; F F Bartol; K M Taylor; A A Wiley; W S Ramsey; T L Ott; 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.    
Journal Detail:
Title:  Biology of reproduction     Volume:  62     ISSN:  0006-3363     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2000 Feb 
Date Detail:
Created Date:  2000-02-25     Completed Date:  2000-02-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  448-56     Citation Subset:  IM    
Center for Animal Biotechnology and Genomics, Albert B. Alkek Institute of Biosciences and Technology, Texas A&M University System Health Science Center, and Department of Animal Science, Texas A&M University, College Station, Texas 77843-2471, USA.
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MeSH Terms
Dinoprost / analogs & derivatives,  blood,  metabolism
Estrus / physiology*
In Situ Hybridization
Oxytocin / pharmacology
Pregnenediones / pharmacology
Progesterone / blood,  metabolism
Receptors, Estrogen / biosynthesis,  drug effects
Receptors, Progesterone / biosynthesis,  drug effects
Uterus / metabolism*
Reg. No./Substance:
0/Pregnenediones; 0/Receptors, Estrogen; 0/Receptors, Progesterone; 25092-41-5/norgestomet; 27376-76-7/15-keto-13,14-dihydroprostaglandin F2alpha; 50-56-6/Oxytocin; 551-11-1/Dinoprost; 57-83-0/Progesterone

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