Conceptus signals for establishment and maintenance of pregnancy.
Conceptus signals for establishment and maintenance of pregnancy.
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DOI：
10.1016/j.anireprosci.2004.04.014
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发表时间：
2004-07-05
期刊：
影响因子：
--
通讯作者：
Bazer, Fuller W
中科院分区：
文献类型：
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作者：
Spencer, Thomas E;Bazer, Fuller W
妊娠的建立和维持是由概念（胚胎/胎儿和相关的胚胎外膜）发出的信号引起的，并且需要黄体（CL）产生的黄体酮。在大多数哺乳动物中，滋养层产生的激素通过直接或间接维持 CL 来维持黄体酮的产生。在家畜（反刍动物和猪）中，来自滋养层的激素具有抗黄体溶解作用，因为它们作用于子宫内膜，阻止子宫释放黄体溶解前列腺素 F2 α (PGF)。在周期性和怀孕的绵羊中，孕酮负向自动调节子宫内膜腔 (LE) 和浅腺上皮 (GE) 中孕酮受体 (PR) 基因的表达。周期性绵羊的现有证据表明，PR 丧失后，上皮雌激素受体 (ER) 和催产素受体 (OTR) 都会增加，从而使催产素诱导子宫释放黄体溶解 PGF 脉冲。在怀孕的绵羊中，孕体滋养层产生干扰素 tau (IFN tau)，作用于子宫内膜，直接抑制 ER α 基因和间接抑制 OTR 基因的转录，从而消除子宫内膜黄体溶解机制的发展。随后，黄体酮、IFN tau、胎盘催乳素 (PL) 和生长激素 (GH) 的连续、重叠作用构成了激素伺服机制，可调节子宫内膜腺形态发生和终末分化功能，以维持绵羊妊娠。在猪中，孕体滋养层产生雌激素，将 PGF 分泌方向从内分泌方向改变为外分泌方向，从而将溶黄体 PGF 隔离在子宫腔内。概念雌激素还能增加子宫内膜 LE 中成纤维细胞生长因子 7 (FGF-7) 的表达，进而刺激表达 FGF-7 受体的滋养外胚层的增殖和分化功能。对这些生理机制的策略性调控可以提供改善子宫容量、概念存活和生殖健康的治疗方案。
Establishment and maintenance of pregnancy results from signaling by the conceptus (embryo/fetus and associated extraembryonic membranes) and requires progesterone produced by the corpus luteum (CL). In most mammals, hormones produced by the trophoblast maintain progesterone production by acting directly or indirectly to maintain the CL. In domestic animals (ruminants and pigs), hormones from the trophoblast are antiluteolytic in that they act on the endometrium to prevent uterine release of luteolytic prostaglandin F2 alpha (PGF). In cyclic and pregnant sheep, progesterone negatively autoregulates expression of the progesterone receptor (PR) gene in the endometrial luminal (LE) and superficial glandular epithelium (GE). Available evidence in cyclic sheep indicates that loss of the PR is closely followed by increases in epithelial estrogen receptors (ER) and then oxytocin receptors (OTR), allowing oxytocin to induce uterine release of luteolytic PGF pulses. In pregnant sheep, the conceptus trophoblast produces interferon tau (IFN tau) that acts on the endometrium to inhibit transcription of the ER alpha gene directly and the OTR gene indirectly to abrogate development of the endometrial luteolytic mechanism. Subsequently, sequential, overlapping actions of progesterone, IFN tau, placental lactogen (PL) and growth hormone (GH) comprise a hormonal servomechanism that regulates endometrial gland morphogenesis and terminal differentiated function to maintain pregnancy in sheep. In pigs, the conceptus trophoblast produces estrogen that alters the direction of PGF secretion from an endocrine to exocrine direction, thereby sequestering luteolytic PGF within the uterine lumen. Conceptus estrogen also increases expression of fibroblast growth factor 7 (FGF-7) in the endometrial LE that, in turn, stimulates proliferation and differentiated functions of the trophectoderm, which expresses the FGF-7 receptor. Strategic manipulation of these physiological mechanisms can offer therapeutic schemes to improve uterine capacity, conceptus survival and reproductive health.