Stenhouse Claire, Newton Makenzie G, Halloran Katherine M, Moses Robyn M, Sah Nirvay, Suva Larry J, Bazer Fuller W
Departments of Animal Science, Texas A&M University, Kleberg Center, TX, 77843-2471, College Station, USA.
Veterinary Physiology and Pharmacology, Texas A&M University, TX, 77843, College Station, USA.
J Anim Sci Biotechnol. 2023 Jan 12;14(1):13. doi: 10.1186/s40104-022-00803-2.
Recent evidence suggests important roles for progesterone (P4) and interferon tau in the regulation of calcium, phosphate, and vitamin D signaling in the uteri of pregnant sheep. However, the effects of P4 and estradiol (E2), with respect to the expression of their receptors PGR and ESR1, respectively, in uterine epithelia on mineral signaling during the estrous cycle has not been investigated. Estrous cycles of mature Suffolk ewes were synchronized, prostaglandin F2α was administered, and ewes were observed for estrus (designated as Day 0) in the presence of vasectomized rams. On Days 1, 9, or 14 of the estrous cycle, hysterectomies were performed.
25-hydroxyvitamin D was more abundant in plasma from ewes on Day 14 than Day 1 (P < 0.05). Expression of fibroblast growth factor receptor 2 (FGFR2), a disintegrin and metalloprotease 17 (ADAM17), and parathyroid hormone-related protein (PTHrP) mRNAs was greater in endometria on Day 9 compared to Days 1 and 14 (P < 0.01). Similarly, expression of transient receptor potential cation channel subfamily V member 6 (TRPV6) mRNA was greater in endometria on Day 9 than Day 1 (P < 0.05). ATPase plasma membrane Ca transporting 4 (ATP2B4) and S100 calcium binding protein G (S100G) mRNA expression was greater in endometria on Day 14 than on Days 1 and 9 (P < 0.01). In contrast, endometrial expression of vitamin D receptor (VDR) mRNA was lower on Days 9 and 14 than Day 1 (P < 0.01). Expression of klotho (KL) (P < 0.05) and cytochrome P450 family 24 subfamily A member 1 (CYP24) (P < 0.01) mRNAs was lower on Day 14 than Days 1 and 9. ADAM17, FGF23, CYP2R1, CYP27B1, KL, and VDR proteins immunolocalized to the uterine myometrium, blood vessels, and uterine luminal (LE), superficial glandular (sGE), and glandular (GE) epithelia. S100A9 protein was weakly expressed in the uterine myometrium, LE, sGE, and GE. Immunoreactivity of CYP2R1 and KL proteins in uterine LE and sGE was less on Day 1 than on Days 9 and 14. In contrast, S100G protein was expressed exclusively by GE, and immunoreactive S100G protein was less on Day 9. S100A12 protein localized to stromal cells of the uterine stratum spongiosum and blood vessels, but not by uterine epithelial cells.
Collectively, these results implicate E2, P4, and PGR in the regulation of phosphate, calcium, and vitamin D signaling in cyclic ewes.
最近的证据表明,孕酮(P4)和干扰素τ在妊娠绵羊子宫中钙、磷和维生素D信号调节中发挥重要作用。然而,在发情周期中,P4和雌二醇(E2)分别通过其受体PGR和ESR1在子宫上皮细胞中对矿物质信号传导的影响尚未得到研究。对成熟萨福克母羊的发情周期进行同步化处理,注射前列腺素F2α,并在输精管切除的公羊存在的情况下观察母羊发情情况(记为第0天)。在发情周期的第1、9或14天进行子宫切除术。
与第1天相比,第14天母羊血浆中25-羟基维生素D含量更高(P < 0.05)。与第1天和第14天相比,第9天子宫内膜中成纤维细胞生长因子受体2(FGFR2)、解整合素和金属蛋白酶17(ADAM17)以及甲状旁腺激素相关蛋白(PTHrP)mRNA的表达更高(P < 0.01)。同样,第9天子宫内膜中瞬时受体电位阳离子通道亚家族V成员6(TRPV6)mRNA的表达高于第1天(P < 0.05)。第14天子宫内膜中ATP酶质膜钙转运4(ATP2B4)和S100钙结合蛋白G(S100G)mRNA表达高于第1天和第9天(P < 0.01)。相反,第9天和第14天子宫内膜中维生素D受体(VDR)mRNA表达低于第1天(P < 0.01)。第14天klotho(KL)(P < 0.05)和细胞色素P450家族24亚家族A成员1(CYP24)(P < 0.01)mRNA表达低于第1天和第9天。ADAM17、FGF23、CYP2R1、CYP27B1、KL和VDR蛋白免疫定位在子宫肌层、血管以及子宫腔(LE)、浅表腺上皮(sGE)和腺上皮(GE)。S100A9蛋白在子宫肌层、LE、sGE和GE中弱表达。子宫LE和sGE中CYP2R1和KL蛋白的免疫反应性在第1天低于第9天和第14天。相反,S100G蛋白仅由GE表达,且第9天免疫反应性S100G蛋白较少。S100A12蛋白定位于子宫海绵层的基质细胞和血管,但子宫上皮细胞不表达。
总体而言,这些结果表明E2、P4和PGR参与调节周期性母羊的磷、钙和维生素D信号传导。