Physiological role of lysophosphatidic acid.

每一次成功的怀孕都需要适当的胚胎植入。（一个特别重要的过程）着床率低是使用辅助生殖技术（ART）治疗不孕不育的一个主要问题。我们报道了一种新的通过溶血磷脂酸（LPA）受体LPA_3/edg 7影响着床的分子机制。LPA_3基因的靶向缺失导致窝仔数显著减少，这可能归因于着床延迟和胚胎间隔改变。这两个事件导致胚胎死亡或胚胎发育延迟以及多个胚胎共享的肥大胎盘。环氧化酶2（考克斯-2）是一种影响着床的酶，在LPA_3缺乏的子宫中，其表达在着床前被下调。考克斯-2产生对着床至关重要的前列腺素^[1]，将前列腺素PGE_2和cPGI外源性注入缺乏LPA_3的雌性小鼠，可以挽救延迟着床，但不能挽救胚胎间距缺陷。这些数据确定LPA_3受体介导的信号作为一个新的影响植入，并进一步表明LPA信号和前列腺素生物合成之间的联系。

Every successful pregnancy requires proper embryo implantation. (a process of particular importance) Poor implantation rate is a major problem during infertility treatments using assisted reproductive technologies (ART). We report a new molecular influence on implantation through the lysophosphatidic acid (LPA) receptor LPA_3/edg7. Targeted deletion of LPA_3 resulted in significantly reduced litter size, which could be attributed to delayed implantation and altered embryo spacing. These two events led to embryo death or delayed embryonic development and hypertrophic placentas shared by multiple embryos. An enzyme demonstrated to influence implantation, cyclooxygenase-2 (COX-2), was down-regulated in LPA_3-deficient uteri during preimplantation. COX-2 produces prostaglandins that are critical for implantation ^1, and exogenous administration of the prostaglandins PGE_2 and cPGI into LPA_3-deficient females rescued delayed implantation but did not rescue defects in embryo spacing. These data identify LPA_3 receptor-mediated signaling as a new influence on implantation and further indicate linkage between LPA signalling and prostaglandin biosynthesis.