Impaired Ovulation in Mice with Targeted Deletion of the Neuronal Isoform of Nitric Oxide Synthase
Impaired Ovulation in Mice with Targeted Deletion of the Neuronal Isoform of Nitric Oxide Synthase
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靶向删除一氧化氮合酶神经元亚型导致小鼠排卵受损
DOI：
10.1007/bf03401926
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发表时间：
1998
影响因子：
5.7
通讯作者：
T. Dawson
中科院分区：
文献类型：
--
作者：
S. Klein;D. Carnovale;A. Burnett;E. Wallach;H. Zacur;J. K. Crone;V. Dawson;R. Nelson;T. Dawson
一氧化氮（NO）在许多生殖过程中起着重要作用。迄今为止，大多数研究都是通过使用一氧化氮前体一氧化氮合酶（NOS）的非特异性药物抑制剂来评估一氧化氮的作用。这些药理NOS抑制剂抑制NOS的所有亚型；因此，每个异构体对女性生殖生理的精确贡献是未知的。本研究的目的是确定神经元NOS （nNOS）在缺乏编码nNOS基因（nNOS−/−）的雌性小鼠的排卵调节中的具体作用。材料和方法野生型（WT）和非nos−/−雌性小鼠通过检测卵巢破裂部位的数量和暴露于外源性促性腺激素（即5 IU妊娠母马血清促性腺激素[PMSG]和5 IU人绒毛膜促性腺激素[hCG]）后从输卵管中恢复的卵母细胞数量来评估排卵。排卵效率以每卵巢破裂点的排卵卵母细胞数来确定。为了研究nNOS - / -小鼠的排卵缺陷是否由于中枢机制的改变，我们对注射25 ng促性腺激素释放激素（GnRH）的WT和nNOS - / -小鼠的血浆促黄体生成素（LH）浓度进行了评估。为了确定nNOS - / -小鼠的排卵缺陷是否由局部排卵过程引起，研究人员检测了WT和nNOS - / -雌性生殖道神经的神经是否存在nNOS蛋白。结果nNOS−/−雌性小鼠存在明显的生育缺陷；自发排卵和促性腺激素刺激排卵后，nNOS - / -小鼠输卵管内卵母细胞数量减少。在nNOS−/−小鼠中，垂体对外源性GnRH的反应是完整的。WT小鼠生殖道神经中可见致密的nNOS蛋白染色。结论nNOS−/−女性的生殖缺陷可能与排卵时卵巢卵母细胞向输卵管转移的改变有关。这些结果提示神经源性一氧化氮生成缺陷可能导致女性不育。
BackgroundNitric oxide (NO) plays an important role in numerous reproductive processes. To date, most studies have assessed the role of NO by using nonspecific pharmacological inhibitors of the precursor to NO, nitric oxide synthase (NOS). These pharmacological NOS inhibitors suppress all isoforms of NOS; thus, the precise contribution of each isoform to female reproductive physiology is unknown. The purpose of this study was to determine the specific role of neuronal NOS (nNOS) in the regulation of ovulation in female mice lacking the gene that encodes for nNOS (nNOS−/−).Materials and MethodsOvulation was assessed in wild-type (WT) and nNOS−/− female mice by examining the number of ovarian rupture sites and number of oocytes recovered from the oviducts following mating or exposure to exogenous gonadotropins (i.e., 5 IU pregnant mares serum gonadotropin [PMSG] and 5 IU human chorionic gonadotropin [hCG]). Ovulatory efficiency was determined as the number of ovulated oocytes per number of ovarian rupture sites. To examine whether ovulatory deficits in nNOS−/− mice were due to alterations in central mechanisms, plasma luteinizing hormone (LH) concentrations were assessed in WT and nNOS−/− mice that were challenged with 25 ng of gonadotropin-releasing hormone (GnRH). To determine whether ovulatory deficits in nNOS−/− mice were due to local ovulation processes, nerves innervating the reproductive tract of WT and nNOS−/− females were examined for the presence of nNOS protein.ResultsThere were substantial fertility deficits in nNOS−/− female mice; the nNOS−/− mice had fewer oocytes in their oviducts following spontaneous and gonadotropin-stimulated ovulation. Pituitary responsiveness to exogenous GnRH challenge was intact in nNOS−/− mice. Dense nNOS protein staining was observed in nerves innervating the reproductive tracts of WT mice.ConclusionsThe reproductive deficits in nNOS−/− females are most likely due to alterations in the transfer of oocytes from the ovaries to the oviducts during ovulation. These results suggest that defects in neuronally derived NO production may contribute to female infertility.
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影响因子：
6.7
作者：
J. Hesla;S. Preutthipan;Michael P. Maguire;T. Chang;Edward E. Wallach;A. Dharmarajan
通讯作者：
J. Hesla;S. Preutthipan;Michael P. Maguire;T. Chang;Edward E. Wallach;A. Dharmarajan
Interleukin-1 beta 刺激大鼠卵巢中亚硝酸盐的产生：异源细胞间相互作用和胰岛素介导的一氧化氮合酶诱导亚型调节的证据。
影响因子：
3.6
作者：
Ben-Shlomo,I;Kokia,E;Jackson,MJ;Adashi,EY;Payne,DW
通讯作者：
Payne,DW
Interleukin-1 对培养的大鼠卵巢细胞具有形态发生作用和细胞毒性：对于异源、不依赖于接触的细胞间相互作用具有必然作用。
影响因子：
4.8
作者：
Hurwitz,A;Hernandez,ER;Payne,DW;Dharmarajan,AM;Adashi,EY
通讯作者：
Adashi,EY
一氧化氮在体内和体外控制黄体生成素释放激素释放中的作用。
DOI：
10.1073/pnas.90.21.10130
发表时间：
1993
影响因子：
11.1
作者：
Rettori,V;Belova,N;Dees,WL;Nyberg,CL;Gimeno,M;McCann,SM
通讯作者：
McCann,SM
促性腺激素刺激的血卵泡屏障调节是由一氧化氮介导的。
DOI：
10.1152/ajpendo.1995.269.2.e290
发表时间：
1995
期刊：
The American journal of physiology.
影响因子：
--
作者：
Powers,RW;Chen,L;Russell,PT;Larsen,WJ
通讯作者：
Larsen,WJ