Joyce Margaret M, Burghardt James R, Burghardt Robert C, Hooper R Neil, Jaeger Laurie A, Spencer Thomas E, Bazer Fuller W, Johnson Greg A
Center for Animal Biotechnology and Genomics, Texas A&M University, College Station, Texas 77843-4458, USA.
Biol Reprod. 2007 Aug;77(2):292-302. doi: 10.1095/biolreprod.107.060939. Epub 2007 May 2.
Pig conceptuses secrete estrogen for pregnancy recognition, and they secrete interferons (IFNs) gamma and delta during the peri-implantation period. The uterine effects of pig IFNs are not known, although ruminant conceptuses secrete IFN tau for pregnancy recognition, and this increases the expression of IFN-stimulated genes (ISGs) in the endometrium. In sheep, the transcriptional repressor interferon-regulatory factor 2 (IRF2) is expressed in the endometrial luminal epithelium (LE) and appears to restrict IFN tau induction of most ISGs, including IRF1, to the stroma and glands. Interestingly, MX1, which is an ISG in sheep, is also expressed in the endometrial stroma of pregnant pigs. The objective of the present study was to determine if estrogen and/or conceptus secretory proteins (CSPs) that contain IFNs regulate IRF1 and IRF2 in pig endometria. The endometrial levels of IRF1 and IRF2 were low throughout the estrus cycle. After Day 12 of pregnancy, the levels of the classical ISGs, which include IRF1, STAT2, MIC, and B2M, increased in the overall endometrium, with expression of IRF1 and STAT2 being specifically localized to the stroma. IRF2 increased in the LE after Day 12. To determine the effects of estrogen, pigs were treated with 17 beta-estradiol benzoate (E2). To determine the CSP effects, pigs were treated with E2 and implanted with mini-osmotic pumps that delivered control serum proteins (CX) to one ligated uterine horn and CSP to the other horn. Estrogen increased the level of IRF2 in the endometrial LE. The administration of E2 and infusion of CSP increased the level of IRF1 in the stroma. These results suggest that conceptus estrogen induces IRF2 in the LE and limits the induction of IRF1 by conceptus IFNs to the stroma. The cell-specific expression of IRF1 and IRF2 in the pig endometrium highlights the complex and overlapping events that are associated with gene expression during the peri-implantation period, when pregnancy recognition signaling and uterine remodeling for implantation and placentation are necessary for successful pregnancy.
猪的胚胎分泌雌激素用于妊娠识别，并且在植入前期分泌γ和δ干扰素（IFN）。猪IFN对子宫的影响尚不清楚，尽管反刍动物的胚胎分泌IFNτ用于妊娠识别，并且这会增加子宫内膜中IFN刺激基因（ISG）的表达。在绵羊中，转录抑制因子干扰素调节因子2（IRF2）在内膜腔上皮（LE）中表达，并且似乎将包括IRF1在内的大多数ISG的IFNτ诱导限制在基质和腺体中。有趣的是，绵羊中的一种ISG即MX1，在妊娠母猪的子宫内膜基质中也有表达。本研究的目的是确定雌激素和/或含有IFN的胚胎分泌蛋白（CSP）是否调节猪子宫内膜中的IRF1和IRF2。在整个发情周期中，子宫内膜中IRF1和IRF2的水平都很低。妊娠第12天后，包括IRF1、STAT2、MIC和B2M在内的经典ISG在整个子宫内膜中的水平升高，其中IRF1和STAT2的表达特异性定位于基质。妊娠第12天后，LE中的IRF2增加。为了确定雌激素的作用，给猪注射苯甲酸雌二醇（E2）。为了确定CSP的作用，给猪注射E2并植入微型渗透泵，向一侧结扎的子宫角输送对照血清蛋白（CX），向另一侧子宫角输送CSP。雌激素增加了子宫内膜LE中IRF2的水平。注射E2并输注CSP增加了基质中IRF1的水平。这些结果表明，胚胎雌激素在LE中诱导IRF2，并将胚胎IFN对IRF1的诱导限制在基质中。猪子宫内膜中IRF1和IRF2的细胞特异性表达突出了植入前期与基因表达相关的复杂且重叠的事件，此时妊娠识别信号以及为植入和胎盘形成进行的子宫重塑对于成功妊娠是必要的。
