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【bio-news】生殖生理：肾上腺髓质素单倍剂量不足
Female Reproductive Tract
Haploinsufficiency for Adrenomedullin Reduces Pinopodes and Diminishes Uterine Receptivity in Mice
Manyu Li , Yongqin Wu , and Kathleen M. Caron *
* To whom correspondence should be addressed. E-mail: kathleen_caron@med.unc.edu .
Abstract
Adrenomedullin (AM) is a multifunctional peptide vasodilator that signals through a G-protein coupled receptor called calcitonin receptor-like receptor (CL), when the receptor is associated with a receptor activity modifying protein 2 (RAMP2).
We previously demonstrated that haploinsufficieny for each of these genes led to reduced maternal fertility and that even a modest genetic reduction of AM peptide caused maternal defects in implantation, placentation and fetal growth.
Here we further demonstrate that Adm+/- female mice displayed reduced pregnancy success rates that were not caused by defects in folliculogenesis, ovulation or fertilization.
The poor fertility of Adm+/- female mice could not be rescued by transfer of wildtype blastocysts, which suggested an underlying defect in uterine receptivity.
In fact, we found that Adm, Calcrl and Ramp2 gene expression are tightly and spatiotemporally regulated in the luminal epithelial cells of the uterus during the estrous cycle and the peri-implantation period.
RAMP3, which also generates an AM receptor when associated with CL, had a diametrically opposite expression pattern than that of Adm, Calcrl and Ramp2 and was most robustly induced in the stroma of the uterus.
Finally, we discovered that Adm+/- female mice have a substantially reduced number of pinopodes on the uterine luminal epithelial surface, which is indicative and possibly causative of the poor uterine receptivity. Taken together, our studies identify a new class of pharmacologically tractable proteins that are involved in establishing uterine receptivity through the regulation of pinopode formation.
Key words: Female Reproductive Tract • Implantation • Uterus • Gene Targeted Mouse models • pinopode Haploinsufficiency for Adrenomedullin Reduces Pinopodes and Diminishes Uterine Receptivity in Mice
肾上腺髓质素单倍剂量不足减少了小鼠胞饮突数目，使子宫内膜容受性建立受限
Manyu Li , Yongqin Wu , and Kathleen M. Caron *
* To whom correspondence should be addressed. E-mail: kathleen_caron@med.unc.edu .
Abstract
Adrenomedullin (AM) is a multifunctional peptide vasodilator that signals through a G-protein coupled receptor called calcitonin receptor-like receptor (CL), when the receptor is associated with a receptor activity modifying protein 2 (RAMP2).
肾上腺髓质素（ AM ）是一种多功能血管舒张多肽，通过G蛋白偶联受体所谓的降钙素受体样受体（CL）传递信号，此受体可与受体活性修饰蛋白2(RAMP2)交联。
We previously demonstrated that haploinsufficieny for each of these genes led to reduced maternal fertility and that even a modest genetic reduction of AM peptide caused maternal defects in implantation, placentation and fetal growth.
我们先前实验表明这些基因的任何一个单倍剂量不足都可以导致女性生育力下降，即使AM多肽的遗传缺陷非常轻微也会引起母体的胚胎植入，胎盘化和胎儿生长发育受限。
Here we further demonstrate that Adm+/- female mice displayed reduced pregnancy success rates that were not caused by defects in folliculogenesis, ovulation or fertilization.
本研究中我们进一步揭示了Adm+/-雌性小鼠怀孕的成功率下降，并非与卵泡生长失败、排卵或者受精缺陷有关。
The poor fertility of Adm+/- female mice could not be rescued by transfer of wildtype blastocysts, which suggested an underlying defect in uterine receptivity.
Adm+/-雌性小鼠生育力下降，而且不能通过植入野生型小鼠的卵泡来逆转，表明这些小鼠存在子宫内膜容受性缺陷。
In fact, we found that Adm, Calcrl and Ramp2 gene expression are tightly and spatiotemporally regulated in the luminal epithelial cells of the uterus during the estrous cycle and the peri-implantation period.
事实上，在月经周期和围植入期子宫内膜腔上皮细胞表达Adm, Calcrl 和 Ramp2基因是经过非常严密的调控的，以使这些基因的在特定的时间和空间表达。
RAMP3, which also generates an AM receptor when associated with CL, had a diametrically opposite expression pattern than that of Adm, Calcrl and Ramp2 and was most robustly induced in the stroma of the uterus.
RAMP3在与CL交联时可以产生AM受体，并且可以自行在子宫基质诱导合成AM受体，这与CL与Adm, Calcrl 和 Ramp2相交联时完全不同。
Finally, we discovered that Adm+/- female mice have a substantially reduced number of pinopodes on the uterine luminal epithelial surface, which is indicative and possibly causative of the poor uterine receptivity. Taken together, our studies identify a new class of pharmacologically tractable proteins that are involved in establishing uterine receptivity through the regulation of pinopode formation.
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作者:admin@医学,生命科学 2011-01-03 17:53
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