Cytokines and Pregnancy Recognition

Bazer, Fuller W.; Spencer, Thomas E.; Ott, Troy L.; Johnson, Howard M.

doi:10.1007/978-1-4613-8422-9_4

Cited by 5 publications

(3 citation statements)

References 77 publications

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“…During early pregnancy, the ruminant conceptus produces IFN-T, which inhibits formation of ER and OTR on the endometrial epithelium and prevents pulsatile release of luteolytic PGF 2 . [22]. The biological mechanism(s) whereby IFN-t signals maternal recognition of pregnancy in the ovine uterus has not been determined.…”

Section: Discussionmentioning

confidence: 97%

“…In both cyclic and pregnant ewes, endometrial production of luteolytic prostaglandin F 2 , (PGF 2 ,) is regulated by complex interactions between estrogen, progesterone, oxytocin, and their respective receptors in the uterus [13,[19][20][21][22]. Endometrial steroid hormone receptor populations change in sheep during the estrous cycle and pregnancy [12,13,23,24].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Temporal and Spatial Alterations in Uterine Estrogen Receptor and Progesterone Receptor Gene Expression During the Estrous Cycle and Early Pregnancy in the Ewe1

Spencer

Bazer

1995

Biology of Reproduction

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290

208

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Mechanisms regulating responses of the ovine uterus to endocrine and paracrine signals during the estrous cycle and pregnancy are likely to require tissue- and cell-specific regulation of steroid hormone receptor gene expression. To determine effects of day and pregnancy status (cyclic or pregnant) on uterine estrogen receptor (ER) and progesterone receptor (PR) gene expression, ewes were hysterectomized either on Day 1 (Day 0 = estrus/mating), 6, 11, 13, or 15 of the estrous cycle (n = 3/day) or on Day 11, 13, 15, 17, or 25 of early pregnancy (n = 5/day). Steady state levels of ER and PR mRNA were determined in endometrial and myometrial tissues by slot-blot hybridization and ribonuclease protection assays, respectively, using homologous ovine ER and PR cRNA probes. Changes in spatial expression of ER and PR mRNA and protein in uterine tissue sections were determined by in situ hybridization and immunocytochemical analyses. In cyclic ewes, steady state levels of endometrial ER mRNA were highest on Day 1, declined between Days 1 and 6, and increased between Days 11 and 15. However in pregnant ewes, endometrial ER mRNA levels decreased between Days 11 and 15 and increased slightly between Days 15 and 25. In cyclic ewes, levels of myometrial ER mRNA were highest on Day 1, decreased to Day 6, and remained low thereafter. In cyclic ewes, endometrial PR mRNA levels were highest on Day 1, decreased between Days 1 and 11, and then increased between Days 13 and 15. In cyclic ewes, myometrial PR mRNA levels were highest on Day 1 and declined thereafter. Endometrial PR mRNA levels were not different between cyclic and pregnant ewes on Days 11, 13, and 15. In pregnant ewes, PR mRNA levels were low on Day 11, increased between Days 11 and 17, and decreased between Days 17 and 25. In pregnant ewes, myometrial PR mRNA levels were low and did not change between Days 11 and 25. In situ hybridization and immunocytochemical analyses revealed distinct tissue- and cell type-specific alterations in uterine ER and PR mRNA and protein expression during the estrous cycle and early pregnancy that generally paralleled overall changes in steady state levels of ER and PR mRNAs. In the endometrium, the most striking observation was that PR mRNA and protein expression disappeared from the luminal and shallow glandular epithelium between Days 6 and 13 of the estrous cycle, whereas ER mRNA and protein expression was low on Days 6 and 11 and increased between Days 11 and 15 in the luminal and shallow glandular epithelium. During early pregnancy, expression of ER and PR mRNAs, as well as ER and PR protein, was very low or absent in the luminal and shallow glandular epithelium between Days 13 and 25 of pregnancy. Moreover, ER and PR mRNA and protein were consistently present at low levels in the stroma and deep glandular epithelium in both cyclic (Days 11-15) and pregnant (Days 11-25) ewes. Collectively, results suggest that uterine ER and PR gene expression is regulated in a tissue- and cell type-specific manner during the estrous cycle and early...

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Temporal and Spatial Alterations in Uterine Estrogen Receptor and Progesterone Receptor Gene Expression During the Estrous Cycle and Early Pregnancy in the Ewe1

Spencer

Bazer

1995

Biology of Reproduction

Self Cite

290

208

View full text Add to dashboard Cite

show abstract

“…Future studies in mice deficient in IFN-␥ and its receptor [38,39] may assist in defining these pathways even though compensation by Type I IFNs [40] may confound interpretations of the results, as has been the case with other functionally redundant cytokines and growth factors in the uterus. a Hybridization signal intensities are an average determined by two independent readers as ND, cell type or tissue not detected; 0, no IFN-␥ mRNA detected; ϩ/Ϫ, weakly positive hybridization signal; ϩ, positive hybridization signal; ϩϩ, strongly positive hybridization signal.…”

Section: Discussionmentioning

confidence: 99%

Interferon-γ gene expression in cycling and pregnant mouse uterus: temporal aspects and cellular localization

Platt

Hunt

1998

Journal of Leukocyte Biology

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Ovine Interferon-τ Regulates Expression of Endometrial Receptors for Estrogen and Oxytocin but not Progesterone1

Spencer

Becker

George

et al. 1995

Biology of Reproduction

131

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Ovine interferon-tau (oIFN-tau) may stabilize endometrial progesterone receptor (PR) and/or inhibit estrogen receptor (ER) gene expression during pregnancy recognition to suppress endometrial oxytocin receptor (OTR) formation and production of luteolytic prostaglandin (PG) F2 alpha pulses. This study determined whether or not oIFN-tau stabilized PR expression in the endometrium during PR down-regulation by continuous exposure to progesterone. Twenty cyclic ewes were bilaterally ovariectomized and fitted with uterine catheters on Day 2 of the estrous cycle (Day 0 = estrus). Ewes were then assigned randomly to be treated, in a 2 x 2 factorial arrangement, with recombinant oIFN-tau (roIFN-tau; 2 x 10(7) antiviral units per ewe per day) or control proteins (6 mg/day) by intrauterine injection from Days 10 to 14, and with daily i.m. injections of 20 mg progesterone from Days 2 to 14 (P) or progesterone from Days 2 to 14 plus 50 micrograms estradiol-17 beta from Days 12 to 14 (P+E). All ewes were hysterectomized on Day 15. Endometrial PR mRNA (p < 0.01) and protein (p < 0.03) were higher in ewes receiving P+E than in those receiving P alone. However, the increase in PR mRNA and protein was not as great in the endometrium of roIFN-tau-treated ewes as compared to controls (p < 0.08, treatment x steroid). In ewes receiving P alone, PR mRNA and immunoreactive PR were localized to stroma and deep glandular epithelium and were not present in endometrial luminal and shallow glandular epithelium. Values for endometrial ER mRNA (p < 0.02) and ER protein (p < 0.01) were greater in controls than in roIFN-tau-treated ewes regardless of steroid treatment. Among controls, ER mRNA and immunoreactive ER protein were present in the luminal and glandular epithelium and were increased in the epithelium and stroma in ewes receiving estrogen. In contrast, endometrial ER mRNA and immunoreactive ER protein were very low or absent in the endometrium of roIFN-tau-treated ewes and were not increased by estrogen. Among controls, endometrial OTR density was greater (p < 0.09) in ewes treated with P+E than in those treated with P alone. In roIFN-tau-treated ewes, endometrial OTR density was lower (p < 0.01) than in the controls. Results indicate that roIFN-tau did not stabilize or prevent autologous down-regulation of PR mRNA or protein expression in the endometrium. However, roIFN-tau did suppress endometrial ER expression and OTR formation in ewes regardless of steroid treatment. The results support the hypothesis that the antiluteolytic effects of oIFN-tau are to suppress endometrial ER gene expression in the endometrial epithelium, thereby inhibiting formation of OTR and production of luteolytic PGF2 alpha pulses.

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Cytokines and Pregnancy Recognition

Cited by 5 publications

References 77 publications

Temporal and Spatial Alterations in Uterine Estrogen Receptor and Progesterone Receptor Gene Expression During the Estrous Cycle and Early Pregnancy in the Ewe1

Temporal and Spatial Alterations in Uterine Estrogen Receptor and Progesterone Receptor Gene Expression During the Estrous Cycle and Early Pregnancy in the Ewe1

Interferon-γ gene expression in cycling and pregnant mouse uterus: temporal aspects and cellular localization

Ovine Interferon-τ Regulates Expression of Endometrial Receptors for Estrogen and Oxytocin but not Progesterone1

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