Synergistic role of nitric oxide and progesterone during the establishment of pregnancy in the rat
Synergistic role of nitric oxide and progesterone during the establishment of pregnancy in the rat
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DOI：
10.1093/humrep/14.2.542
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发表时间：
1999-02-01
影响因子：
6.1
通讯作者：
Garfield, RE
中科院分区：
文献类型：
--
作者：
Chwalisz, K;Winterhager, E;Garfield, RE
成功的妊娠严格依赖于滋养层-蜕膜的相互作用和着床部位的充足血液供应。一氧化氮（NO）已被证明在妊娠晚期发挥重要作用，尽管其在妊娠早期的作用尚不清楚。本研究的目的是评估NO是否在着床前[着床后（p.c.）1-4天]发挥作用。和围着床期（交配后6-8天）怀孕的各个阶段。在存在和不存在低剂量抗孕酮、奥那司酮的情况下，用非特异性一氧化氮合酶（NOS）抑制剂N-G-硝基-L-精氨酸甲酯（L-NAME）和iNOS抑制剂氨基胍处理大鼠，并在p，c.和19 p，c，。植入前，单独治疗（L-NAME，氨基胍，奥那司酮）对妊娠结局影响不大。相反，氨基胍加奥那司酮治疗完全阻止了妊娠，而L-NAME加奥那司酮将妊娠率降低至约50%。此外，两种治疗均显著降低了蜕膜化。输卵管推进实验显示，在p，c第1-4天，氨基胍加奥那司酮治疗后，胚胎发育停滞在8细胞期左右。类似地，在围着床期用L-NAME、氨基胍和奥那司酮治疗对妊娠的影响都很小。然而，L-NAME和奥那司酮的组合以及氨基胍和奥那司酮的组合分别在71%和42%的织补中阻止了妊娠，如在p，c第19天测定的。这些处理也明显抑制蜕膜化过程。这项研究表明，NOS抑制剂和抗孕激素的协同作用，防止怀孕。NOS，特别是细胞因子和孕酮诱导的iNOS，可能代表一个新的目标，新的治疗药物能够促进或抑制妊娠。
Successful pregnancy is strictly dependent on the trophoblast-decidual interaction and on an adequate blood supply to the implantation sites. Nitric oxide (NO) has been shown to play an important role during advanced gestation, although its role during early pregnancy is unclear. The aim of the present study in rats was to evaluate whether NO plays a role during the preimplantation [days 1-4 post coitum (p.c.)] and peri-implantation (days 6-8 p.c.) phases of pregnancy. The rats were treated with the non-specific nitric oxide synthase (NOS) inhibitor N-G-nitro-L-arginine methyl ester (L-NAME), and the iNOS inhibitor aminoguanidine in the presence and absence of low-dose antiprogestin, onapristone, and evaluated on days 9 p,c. and 19 p,c,, respectively. Before implantation, the treatments alone (L-NAME, aminoguanidine, onapristone) had little effect on pregnancy outcome. Conversely, aminoguanidine plus onapristone treatment completely prevented pregnancy, whereas L-NAME plus onapristone reduced the pregnancy rate to approximately 50%, In addition, both treatments drastically reduced decidualization, Oviductal pushing experiments revealed arrest of embryo development at around the 8-cell stage after aminoguanidine plus onapristone treatment on days 1-4 p,c. Similarly treatment during the peri-implantation period with L-NAME, aminoguanidine, and onapristone each had only marginal effects on pregnancy. However, a combination of L-NAME and onapristone, and aminoguanidine plus onapristone prevented pregnancy in 71% and 42% of darns, respectively, as determined on day 19 p,c. These treatments also markedly inhibited the decidualization process. This study demonstrates synergistic effects of NOS inhibitors and an antiprogestin in preventing pregnancy. NOS, particularly the cytokine- and progesterone-inducible iNOS, may represent a new target for novel therapeutic agents capable of promoting or inhibiting pregnancy.