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Protective effects of ethanol extracts of Artemisia asiatica Nakai ex Pamp. on ageing-induced deterioration in mouse oocyte quality

Published online by Cambridge University Press:  21 June 2017

Hyuk-Joon Jeon
Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Korea.
Seung Yeop You
Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Korea.
Dong Hyun Kim
Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Korea. Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam, Korea.
Hong Bae Jeon
Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam, Korea.
Jeong Su Oh*
Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Korea.
All correspondence to: Jeong Su Oh. Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Korea. Tel.: +82 31 290 7865. Fax: +82 31 290 7870. E-mail:


Following ovulation, oocytes undergo a time-dependent deterioration in quality referred to as post-ovulatory ageing. Although various factors influence the post-ovulatory ageing of oocytes, oxidative stress is a key factor involved in deterioration of oocyte quality. Artemisia asiatica Nakai ex Pamp. has been widely used in East Asia as a food ingredient and traditional medicine for the treatment of inflammation, cancer, and microbial infections. Recent studies have shown that A. asiatica exhibits antioxidative effects. In this study, we investigated whether A. asiatica has the potential to attenuate deterioration in oocyte quality during post-ovulatory ageing. Freshly ovulated mouse oocytes were cultured with 0, 50, 100 or 200 μg/ml ethanol extracts of A. asiatica Nakai ex Pamp. After culture for up to 24 h, various ageing-induced oocyte abnormalities, including morphological changes, reactive oxygen species (ROS) accumulation, apoptosis, chromosome and spindle defects, and mitochondrial aggregation were determined. Treatment of oocytes with A. asiatica extracts reduced ageing-induced morphological changes. Moreover, A. asiatica extracts decreased ROS generation and the onset of apoptosis by preventing elevation of the Bax/Bcl-2 expression ratio during post-ovulatory ageing. Furthermore, A. asiatica extracts attenuated the ageing-induced abnormalities including spindle defects, chromosome misalignment and mitochondrial aggregation. Our results demonstrate that A. asiatica can relieve deterioration in oocyte quality and delay the onset of apoptosis during post-ovulatory ageing.

Research Article
Copyright © Cambridge University Press 2017 

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Agarwal, A., Gupta, S., Sekhon, L. & Shah, R. (2008). Redox considerations in female reproductive function and assisted reproduction: from molecular mechanisms to health implications. Antioxid. Redox Signal. 10, 1375–403.CrossRefGoogle ScholarPubMed
Chaube, S.K., Prasad, P.V., Thakur, S.C. & Shrivastav, T.G. (2005). Hydrogen peroxide modulates meiotic cell cycle and induces morphological features characteristic of apoptosis in rat oocytes cultured in vitro . Apoptosis 10, 863–74.CrossRefGoogle ScholarPubMed
Choi, W.J., Banerjee, J., Falcone, T., Bena, J., Agarwal, A. & Sharma, R.K. (2007). Oxidative stress and tumour necrosis factor-α-induced alterations in metaphase II mouse oocyte spindle structure. Fertil. Steril. 88, 1220–31.Google Scholar
de Matos, D.G. & Furnus, C.C. (2000). The importance of having high glutathione (GSH). level after bovine in vitro maturation on embryo development effect of β-mercaptoethanol, cysteine and cystine. Theriogenology 53, 761–71.Google Scholar
Dodson, M.G., Minhas, B.S., Curtis, S.K., Palmer, T.V. & Robertson, J.L. (1989). Spontaneous zona reaction in the mouse as a limiting factor for the time in which an oocyte may be fertilized. J. In Vitro Fert. Embryo. Transf. 6, 101–6.CrossRefGoogle ScholarPubMed
Ducibella, T., Duffy, P., Reindollar, R. & Su, B. (1990). Changes in the distribution of mouse oocyte cortical granules and ability to undergo the cortical reaction during gonadotropin-stimulated meiotic maturation and aging in vivo . Biol. Reprod. 43, 870–6.Google Scholar
Duranthon, V. & Renard, J.P. (2001). The developmental competence of mammalian oocytes: a convenient but biologically fuzzy concept. Theriogenology 55, 1277–89.Google Scholar
Eppig, J.J., Hosoe, M., O'Brien, M.J., Pendola, F.M., Requena, A. & Watanabe, S. (2000). Conditions that affect acquisition of developmental competence by mouse oocytes in. vitro: FSH, insulin, glucose and ascorbic acid. Mol. Cell. Endocrinol. 163, 109–16.Google Scholar
Fissore, R.A., Kurokawa, M., Knott, J., Zhang, M. & Smyth, J. (2002). Mechanisms underlying oocyte activation and postovulatory ageing. Reproduction 124, 745–54.Google Scholar
Fujino, Y., Ozaki, K., Yamamasu, S., Ito, F., Matsuoka, I., Hayashi, E., Nakamura, H., Ogita, S., Sato, E. & Inoue, M. (1996). DNA fragmentation of oocytes in aged mice. Hum. Reprod. 11, 1480–3.Google Scholar
Hahm, K.B., Kim, J.H., You, B.M., Kim, Y.S., Cho, S.W., Yim, H., Ahn, B.O. & Kim, W.B. (1998). Induction of apoptosis with an extract of Artemisia. asiatica attenuates the severity of cerulein-induced pancreatitis in rats. Pancreas 17, 153–7.Google Scholar
Huh, K., Kwon, T.H., Shin, U.S., Kim, W.B., Ahn, B.O., Oh, T.Y. & Kim, J.A. (2003). Inhibitory effects of DA-9601 on ethanol-induced gastrohemorrhagic lesions and gastric xanthine oxidase activity in rats. J. Ethnopharmacol. 88, 269–73.Google Scholar
Longo, F.J. (1981). Changes in the zones pellucidae and plasmalemma of aging mouse eggs. Biol. Reprod. 25, 399411.CrossRefGoogle ScholarPubMed
Lord, T. & Aitken, R.J. (2013). Oxidative stress and ageing of the post-ovulatory oocyte. Reproduction 146, R217–27.Google Scholar
Luberda, Z. (2005). The role of glutathione in mammalian gametes. Reprod. Biol. 5, 517.Google ScholarPubMed
Martin, S.J., Reutelingsperger, C.P., McGahon, A.J., Rader, J.A., van Schie, R.C., LaFace, D.M. & Green, D.R. (1995). Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl . J. Exp. Med. 182, 1545–56.CrossRefGoogle ScholarPubMed
Miao, Y.L., Kikuchi, K., Sun, Q.Y. & Schatten, H. (2009). Oocyte aging: cellular and molecular changes, developmental potential and reversal possibility. Hum. Reprod. Update 15, 573–85.Google Scholar
Nagai, S., Mabuchi, T., Hirata, S., Shoda, T., Kasai, T., Yokota, S., Shitara, H., Yonekawa, H. & Hoshi, K. (2006). Correlation of abnormal mitochondrial distribution in mouse oocytes with reduced developmental competence. Tohoku J. Exp. Med. 210, 137–44.Google Scholar
Oh, T.Y., Ahn, G.J., Choi, S.M., Ahn, B.O. & Kim, W.B. (2005). Increased susceptibility of ethanol-treated gastric mucosa to naproxen and its inhibition by DA-9601, an Artemisia asiatica extract. World J. Gastroenterol. 11, 7450–6.Google Scholar
Oh, T.Y., Lee, J.S., Ahn, B.O., Cho, H., Kim, W.B., Kim, Y.B., Surh, Y.J., Cho, S.W., Lee, K.M. & Hahm, K.B. (2001). Oxidative stress is more important than acid in the pathogenesis of reflux oesophagitis in rats. Gut 49, 364–71.CrossRefGoogle ScholarPubMed
Perez, G.I., Jurisicova, A., Matikainen, T., Moriyama, T., Kim, M.R., Takai, Y., Pru, J.K., Kolesnick, R.N. & Tilly, J.L. (2005). A central role for ceramide in the age-related acceleration of apoptosis in the female germline. FASEB J. 19, 860862.Google Scholar
Premkumar, K.V. & Chaube, S.K. (2013). An insufficient increase of cytosolic free calcium level results postovulatory aging-induced abortive spontaneous egg activation in rat. J. Assist. Reprod. Genet. 30, 117–23.CrossRefGoogle ScholarPubMed
Ryu, B.K., Ahn, B.O., Oh, T.Y., Kim, S.H., Kim, W.B. & Lee, E.B. (1998). Studies on protective effect of DA-9601, Artemisia asiatica extract, on acetaminophen- and CCl4-induced liver damage in rats. Arch. Pharm. Res. 21, 508–13.Google Scholar
Seo, H.J., Park, K.K., Han, S.S., Chung, W.Y., Son, M.W., Kim, W.B. & Surh, Y.J. (2002). Inhibitory effects of the standardized extract (DA-9601) of Artemisia asiatica Nakai on phorbol ester-induced ornithine decarboxylase activity, papilloma formation, cyclooxygenase-2 expression, inducible nitric oxide synthase expression and nuclear transcription factor kappa B activation in mouse skin. Int. J. Cancer 100, 456–62.Google Scholar
Seol, S.Y., Kim, M.H., Ryu, J.S., Choi, M.G., Shin, D.W. & Ahn, B.O. (2004). DA-9601 for erosive gastritis: results of a double-blind placebo-controlled phase III clinical trial. World J. Gastroenterol. 10, 2379–82.Google Scholar
Song, H.J., Shin, C.Y., Oh, T.Y. & Sohn, U.D. (2008). The protective effect of eupatilin on indomethacin-induced cell damage in cultured feline ileal smooth muscle cells: involvement of HO-1 and ERK. J. Ethnopharmacol. 118, 94101.Google Scholar
Steuerwald, N.M., Steuerwald, M.D. & Mailhes, J.B. (2005). Post-ovulatory aging of mouse oocytes leads to decreased MAD2 transcripts and increased frequencies of premature centromere separation and anaphase. Mol. Hum. Reprod. 11, 623–30.Google Scholar
Szollosi, D. (1971). Morphological changes in mouse eggs due to aging in the fallopian tube. Am. J .Anat. 130, 209–25.Google Scholar
Takahashi, T., Takahashi, E., Igarashi, H., Tezuka, N. & Kurachi, H. (2003). Impact of oxidative stress in aged mouse oocytes on calcium oscillations at fertilization. Mol. Reprod. Dev. 66, 143–52.Google Scholar
Tao, Y., Zhou, B., Xia, G., Wang, F., Wu, Z. & Fu, M. (2004). Exposure to l-ascorbic acid or α-tocopherol facilitates the development of porcine denuded oocytes from metaphase I to metaphase II and prevents cumulus cells from fragmentation. Reprod. Domest. Anim. 39, 52–7.Google Scholar
Tarin, J.J., Perez-Albala, S., Aguilar, A., Minarro, J., Hermenegildo, C. & Cano, A. (1999). Long-term effects of postovulatory aging of mouse oocytes on offspring: a two-generational study. Biol. Reprod. 61, 1347–55.CrossRefGoogle ScholarPubMed
Tatone, C., Di Emidio, G., Barbaro, R., Vento, M., Ciriminna, R. & Artini, P.G. (2011). Effects of reproductive aging and postovulatory aging on the maintenance of biological competence after oocyte vitrification: insights from the mouse model. Theriogenology 76, 864–73.Google Scholar
Wakayama, S., Thuan, N.V., Kishigami, S., Ohta, H., Mizutani, E., Hikichi, T., Miyake, M. & Wakayama, T. (2004). Production of offspring from one-day-old oocytes stored at room temperature. J. Reprod. Dev. 50, 627–37.CrossRefGoogle ScholarPubMed
Winston, N.J., Braude, P.R. & Johnson, M.H. (1993). Are failed-fertilized human oocytes useful? Hum. Reprod. 8, 503–7.Google Scholar
Xu, Z., Abbott, A., Kopf, G.S., Schultz, R.M. & Ducibella, T. (1997). Spontaneous activation of ovulated mouse eggs: time-dependent effects on M-phase exit, cortical granule exocytosis, maternal messenger ribonucleic acid recruitment, and inositol 1,4,5-trisphosphate sensitivity. Biol. Reprod. 57, 743–50.Google Scholar
Zhang, N., Wakai, T. & Fissore, R.A. (2011). Caffeine alleviates the deterioration of Ca2+ release mechanisms and fragmentation of in vitro-aged mouse eggs. Mol. Reprod. Dev. 78, 684701.CrossRefGoogle ScholarPubMed