哺乳动物排卵过程复杂,包括卵泡发育、卵泡成熟破裂后的排卵以及黄体形成和退化等过程。目前研究表明,排卵过程受低氧微环境和响应低氧条件的因子—低氧诱导因子(Hypoxic inducible factor, HIF)的影响。低氧调控HIF并影响许多生理过程,如血管生成、炎症反应等。尽管排卵的具体过程早已阐明,但低氧参与调控排卵过程的分子机制并不十分清楚。本文主要综述了哺乳动物在排卵过程中低氧环境如何产生以及HIF如何调控该过程的分子机制,旨在进一步理解排卵机制和卵巢的综合性功能,为相关的卵巢疾病提供一定的理论依据。
Mammalian ovulation is a complicated process that includes development of follicles, ovulation, formation of corpus luteum and luteolysis. The three different stages of the ovulation activity are affected by hypoxic microenvironment and hypoxia-induced factors (HIF), which play a crucial role in physiologyical processes, such as angiogenesis and inflammation. Although the process of ovulation has been well elucidated, the molecular mechanism regulated by hypoxia needs an in depth study. In this review, we summarize how hypoxic and HIF regulate gene expression during mammalian ovulation in order to provide a better understanding of ovulation mechanism, which may lay a theoretical basis for prevention and therapy of various ovarian diseases.
[1] Breen SM, Andric N, Ping T, Xie F, Offermans S, Gossen JA, Ascoli M. Ovulation involves the luteinizing hormone- dependent activation of Gq/11 in granulosa cells. Mol Endocrinlo , 2013, 27(9): 1483-1491.
[2] Nishimura R, OkudaA K. Multiple roles of hypoxia in ovarian function: roles of hypoxia-inducible factor-related and -unrelated signals during the luteal phase. Reprod Fertil Dev , 2015.
[3] Tam KK, Russell DL, Peet DJ, Bracken CP, Rodgers RJ, Thompson JG, Kind KL. Hormonally regulated follicle differentiation and luteinization in the mouse is associated with hypoxia inducible factor activity. Mol Cell Endocrinol , 2010, 327(1-2): 47-55.
[4] Hashimoto T, Shibasaki T. Hypoxia-inducible factor as an angiogenic master switch. Front Pediatr , 2015, 3: 33.
[5] Takacova M, Pastorekova S. Tumour hypoxia-molecular mechanisms and clinical relevance. Klin Onkol, 2015, 28(3): 183-190.
[6] Li QF, Dai AG. Progress of HIFs. Journal of Medical Molecular Biology (wuhan) , 2003, 25(4): 219-223. 李启芳, 戴爱国. 低氧诱导因子家族研究进展. 国外医学分子生物学分册, 2003, 25(4): 219-223.
[7] Semenza GL, Wang GL. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol , 1992, 12(12): 5447-5454.
[8] Ema M, Taya S, Yokotani N, Sogawa K, Matsuda Y, Fujii-Kuriyama Y. A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1alpha regulates the VEGF expression and is potentially involved in lung and vascular?development. Proc Natl Acad Sci USA , 1997, 94(9): 4273-4278.
[9] Gu YZ, Moran SM, Hoqenesch JB, Wartman L, Bradfield CA. Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3alpha. Gene Expr , 1998, 7(3): 205-213.
[10] Pawlus MR, Cheng JH. Enhanceosomes as integrators of hypoxia inducible factor (HIF) and other transcription factors in the hypoxic transcriptional response. Cell Signal , 2013, 25(9): 1895-1903.
[11] Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM , Lane WS, Kaelin WG Jr. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Scince , 2001, 292(5516): 464-468.
[12] Ivan M, Kaelin WG Jr. The von Hippel-Lindau tumor suppressor protein. Curr Opin Genet Dev , 2001, 11(1): 27-34.
[13] Lisztwan J, Imbert G, Wirbelauer C, Gstaiger M, Krek W. The von Hippel-Lindau tumor suppressor protein is a component of an E3 ubiquitin-protein ligase activity. Genes Dev , 1999, 13(14): 1822-1833.
[14] Iwai K, Yamanaka K, Kamura T, Minato N, Conaway RC, Conaway JW, Klausner RD, Pause A. Identification of the von Hippel-Lindau tumor-suppressor protein as part of an active E3 ubiquitin ligase complex. Proc Natl Acad Sci USA , 1999, 96(22): 12436-12441.
[15] Heikkila M, Pasanen A, Kivirikko KI, Myllyharju J. Roles of the human hypoxia-inducible factor (HIF)-3α variantsin the hypoxia response. Cell Mol Life Sci , 2011, 68(23): 3885-3901.
[16] Chen L, Endler A, Shibasaki F. Hypoxia and angiogenesis: regulation of hypoxia-inducible factors via novel binding factors. Exp Mol Med , 2009, 41(12): 849-857.
[17] Cockman ME, Masson N, Mole DR, Jaakkola P, Chang GW, Clifford SC, Maher ER, Pugh CW, Ratcliffe PJ, Maxwell PH. Hypoxia inducible factor-alpha binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein. J Biol Chem , 2000, 275(33): 25733-25741.
[18] Zhao YZ, Liu XL, Shen GM, Ma YN, Zhang FL, Chen MT, Zhao HL, Yu J, Zhang JW. Hypoxia induces peroxisome proliferator-activated receptor γ expression via HIF-1- dependent mechanisms in HepG2 cell line. Arch Biochem Biophys , 2014, 543: 40-47.
[19] Pawlus MR, Wang L, Murakami A, Dai G, Hu CJ. STAT3 or USF2 contributes to HIF target gene specificity. PLoS One , 2013, 8(8): e72358.
[20] Pawlus MR , Wang L , Hu CJ. STAT3 and HIF1&
