Spencer T E, Becker W C, George P, Mirando M A, Ogle T F, Bazer F W
Department of Animal Science, Texas A&M University, College Station 77843-2471, USA.
Biol Reprod. 1995 Sep;53(3):732-45. doi: 10.1095/biolreprod53.3.732.
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.
绵羊干扰素 -τ（oIFN -τ）在妊娠识别期间可能会稳定子宫内膜孕酮受体（PR）和/或抑制雌激素受体（ER）基因表达，以抑制子宫内膜催产素受体（OTR）的形成以及黄体溶解前列腺素（PG）F2α脉冲的产生。本研究确定了在持续暴露于孕酮导致PR下调期间，oIFN -τ是否能稳定子宫内膜中的PR表达。20只处于发情周期的母羊在发情周期的第2天（第0天 = 发情期）进行双侧卵巢切除并植入子宫导管。然后，母羊被随机分配，按照2×2析因设计，从第10天至第14天通过子宫内注射接受重组oIFN -τ（roIFN -τ；每只母羊每天2×10⁷抗病毒单位）或对照蛋白（6毫克/天），并从第2天至第14天每天肌肉注射20毫克孕酮（P），或从第2天至第14天注射孕酮并从第12天至第14天注射50微克雌二醇 -17β（P + E）。所有母羊在第15天进行子宫切除。接受P + E的母羊子宫内膜PR mRNA（p < 0.01）和蛋白（p < 0.03）水平高于仅接受P的母羊。然而，与对照组相比，roIFN -τ处理的母羊子宫内膜中PR mRNA和蛋白的增加幅度较小（p < 0.08，处理×类固醇）。在仅接受P的母羊中，PR mRNA和免疫反应性PR定位于基质和深层腺上皮，而不存在于子宫内膜腔和浅层腺上皮中。无论类固醇处理如何，对照组的子宫内膜ER mRNA（p < 0.02）和ER蛋白（p < 0.01）值均高于roIFN -τ处理的母羊。在对照组中，ER mRNA和免疫反应性ER蛋白存在于腔上皮和腺上皮中，并且在接受雌激素的母羊的上皮和基质中增加。相比之下，roIFN -τ处理的母羊子宫内膜中ER mRNA和免疫反应性ER蛋白非常低或不存在，并且不会因雌激素而增加。在对照组中，接受P + E处理的母羊子宫内膜OTR密度高于仅接受P处理的母羊（p < 0.09）。在roIFN -τ处理的母羊中，子宫内膜OTR密度低于对照组（p < 0.01）。结果表明，roIFN -τ不能稳定或阻止子宫内膜中PR mRNA或蛋白表达的自身下调。然而，无论类固醇处理如何，roIFN -τ确实抑制了母羊子宫内膜ER表达和OTR形成。这些结果支持了以下假设：oIFN -τ的抗黄体溶解作用是通过抑制子宫内膜上皮中的ER基因表达，从而抑制OTR的形成和黄体溶解PGF2α脉冲的产生。
