Ghrelin inhibits the development of mouse preimplantation embryos in vitro

Ghrelin inhibits the development of mouse preimplantation embryos in vitro
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DOI:
10.1210/en.2003-0033
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发表时间:
2003-06-01
期刊:
影响因子:
4.8
通讯作者:
Tanaka, T
Tanaka, T
中科院分区:
医学2区
文献类型:
--
作者:
Kawamura, K;Sato, N;Tanaka, T

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尽管生长素释放肽在中枢神经系统中充当摄食行为和能量代谢的调节剂,但最近的研究表明生长素释放肽在生殖组织中的外周作用。在这里,我们研究了小鼠卵母细胞和植入前胚胎中生长素释放肽及其受体(GHS-R)的表达,并研究了生长素释放肽在调节早期胚胎发育中的作用。 ghrelin 和 GHS-R mRNA 在桑椹胚或更晚期的胚胎阶段均被检测到。至于ghrelin的起源,ghrelin mRNA和蛋白质均在子宫内膜中被鉴定。与自由进食的动物相比,禁食小鼠子宫液和血浆中的生长素释放肽水平显着增加。在培养基中添加生长素释放肽抑制了两细胞胚胎向孵化囊胚的发育,并且生长素释放肽的抑制作用被GHS-R拮抗剂消除。此外,生长素释放肽显着减少囊胚中的总细胞、内细胞团和滋养外胚层细胞的数量。这些观察结果表明,饥饿素可以在禁食期间抑制植入前胚胎的发育。因此,生长素释放肽可能充当外围因素,以避免营养不良状态下怀孕造成的过量代谢需求。
Although ghrelin acts as a modulator of feeding behavior and energy metabolism in the central nervous system, recent studies have implicated the peripheral actions of ghrelin in reproductive tissues. Here, we investigated the expression of ghrelin and its receptor (GHS-R) in mouse oocyte and preimplantation embryos, and we examined the role of ghrelin in the regulation of early embryo development. Both ghrelin and GHS-R mRNAs were detected in morula or more advanced embryo stages. As for the origin of ghrelin, both ghrelin mRNA and protein were identified in the uterine endometrium. The levels of ghrelin in uterine fluid as well as plasma were significantly increased in fasting mice compared with animals with free access to foods. Addition of ghrelin to culture media inhibited the development of two-cell embryos to the hatched blastocysts, and the inhibitory effects of ghrelin were abolished by an antagonist for the GHS-R. In addition, ghrelin significantly decreased the number of total cells, inner cell mass, and trophectoderm cells in blastocysts. These observations suggest that ghrelin could inhibit the development of preimplantation embryos during fasting. Thus, ghrelin may act as a peripheral factor to avoid the excess metabolic demands imposed by pregnancy during malnutritional states.