Hu Junting, Ma Shulan, Zou Sien, Li Xin, Cui Peng, Weijdegård Birgitta, Wu Gencheng, Shao Ruijin, Billig Håkan, Feng Yi
Department of Integrative Medicine and Neurobiology, State Key Lab of Medical Neurobiology, Shanghai Medical College and Institute of Acupuncture Research (WHO Collaborating Center for Traditional Medicine), Institute of Brain Science, Fudan University, Shanghai 200032, China.
Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China.
Int J Mol Sci. 2014 Dec 23;16(1):49-67. doi: 10.3390/ijms16010049.
Nitric oxide (NO) is highly unstable and has a half-life of seconds in buffer solutions. It is synthesized by NO-synthase (NOS), which has been found to exist in the following three isoforms: neuro nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS). NOS activity is localized in the reproductive tracts of many species, although direct evidence for NOS isoforms in the Fallopian tubes of mice is still lacking. In the present study, we investigated the expression and regulation of NOS isoforms in the mouse and human Fallopian tubes during the estrous and menstrual cycles, respectively. We also measured isoform expression in humans with ectopic pregnancy and in mice treated with lipopolysaccharide (LPS). Our results confirmed the presence of different NOS isoforms in the mouse and human Fallopian tubes during different stages of the estrous and menstrual cycles and showed that iNOS expression increased in the Fallopian tubes of women with ectopic pregnancy and in LPS-treated mice. Elevated iNOS activity might influence ovulation, cilia beats, contractility, and embryo transportation in such a manner as to increase the risk of ectopic pregnancy. This study has provided morphological and molecular evidence that NOS isoforms are present and active in the human and mouse Fallopian tubes and suggests that iNOS might play an important role in both the reproductive cycle and infection-induced ectopic pregnancies.
一氧化氮（NO）极不稳定，在缓冲溶液中的半衰期仅为几秒。它由一氧化氮合酶（NOS）合成，已发现该酶存在以下三种同工型：神经型一氧化氮合酶（nNOS）、诱导型一氧化氮合酶（iNOS）和内皮型一氧化氮合酶（eNOS）。尽管仍缺乏小鼠输卵管中NOS同工型的直接证据，但NOS活性存在于许多物种的生殖道中。在本研究中，我们分别调查了发情周期和月经周期中小鼠和人类输卵管中NOS同工型的表达及调控情况。我们还检测了异位妊娠患者以及用脂多糖（LPS）处理的小鼠中同工型的表达。我们的结果证实，在发情周期和月经周期的不同阶段，小鼠和人类输卵管中存在不同的NOS同工型，并且显示异位妊娠女性的输卵管以及LPS处理的小鼠中iNOS表达增加。升高的iNOS活性可能会以增加异位妊娠风险的方式影响排卵、纤毛摆动、收缩性和胚胎运输。本研究提供了形态学和分子证据，证明NOS同工型存在于人类和小鼠输卵管中并具有活性，表明iNOS可能在生殖周期和感染诱导的异位妊娠中都发挥重要作用。
