The antioxidant curcumin postpones ovarian aging in young and middle-aged mice
Saeideh Hasani Azami A , Hamid Nazarian A , Mohammad Amin Abdollahifar A , Fatemeh Eini B E , Mehdi Allahbakhshian Farsani C and Marefat Ghaffari Novin D E
+ Author Affiliations
- Author Affiliations
A Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Postal code: 1985717443.
B Fertility and Infertility Research Centre, Hormozgan University of Medical Sciences, Bandar Abbas, Iran. Postal code: 7919915519.
C Laboratory Haematology and Blood Bank Department, Faculty of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Postal code: 1971653313.
D Cellular and Molecular Biology Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Postal code: 1985717443.
E Corresponding authors. Emails: mghaffarin@sbmu.ac.ir; feini13@gmail.com
Reproduction, Fertility and Development 32(3) 292-303 https://doi.org/10.1071/RD18472
Submitted: 12 October 2018 Accepted: 4 July 2019 Published: 28 October 2019
Abstract
Reproductive senescence is accompanied by a reduced number and quality of ovarian follicles in response to the accumulation of free radicals and the process of apoptosis. Having selected mice as models, we examined the hypothesis that curcumin as an antioxidant and anti-inflammatory agent might prevent or retard ovarian aging. Female NMRI 21-day-old mice were divided into control, vehicle and curcumin groups. In the treatment group the mice received curcumin at 100 mg kg–1 day–1 intraperitoneally. After 6, 12 and 33 weeks several parameters were examined including ovarian reserve, oocyte quality, oxidative status, in vitro fertilisation and expression of ovulation-related (growth differentiation factor 9 (GDF-9) and bone morphogenetic protein 15 (BMP-15)) and anti-aging-related (sirtuin 1 (SIRT-1) and SIRT-3) genes. Curcumin treatment up to 12 and 33 weeks resulted in increased ovarian volume and number of follicles and was associated with elevated anti-Müllerian hormone and oestrogen and diminished FSH serum levels. Furthermore, enhanced oocyte maturation, fertilisation and embryo development plus reduced oxidative stress were seen in the curcumin group. Also, the expression of GDF-9, BMP-15, SIRT-1 and SIRT-3 genes was increased in the curcumin group. Concerning gestational age, the findings of the study suggested that administration of curcumin could delay the process of oocyte aging in a mouse model.
Additional keywords: in vitro fertilisation, ovarian reserve, oxidative stress, glutathione.
References
Aggarwal, B. B., and Harikumar, K. B. (2009). Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int. J. Biochem. Cell Biol. 41, 40–59.| Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases.Crossref | GoogleScholarGoogle Scholar | 18662800PubMed |
Aktas, C., Kanter, M., and Kocak, Z. (2012). Antiapoptotic and proliferative activity of curcumin on ovarian follicles in mice exposed to whole body ionizing radiation. Toxicol. Ind. Health 28, 852–863.
| Antiapoptotic and proliferative activity of curcumin on ovarian follicles in mice exposed to whole body ionizing radiation.Crossref | GoogleScholarGoogle Scholar | 22075690PubMed |
Al-Suhaimi, E. A., Al-Riziza, N. A., and Al-Essa, R. A. (2011). Physiological and therapeutical roles of ginger and turmeric on endocrine functions. Am. J. Chin. Med. 39, 215–231.
| Physiological and therapeutical roles of ginger and turmeric on endocrine functions.Crossref | GoogleScholarGoogle Scholar | 21476200PubMed |
Anand, P., Kunnumakkara, A. B., Newman, R. A., and Aggarwal, B. B. (2007). Bioavailability of curcumin: problems and promises. Mol. Pharm. 4, 807–818.
| Bioavailability of curcumin: problems and promises.Crossref | GoogleScholarGoogle Scholar | 17999464PubMed |
Appasamy, M., Jauniaux, E., Serhal, P., Al-Qahtani, A., Groome, N. P., and Muttukrishna, S. (2008). Evaluation of the relationship between follicular fluid oxidative stress, ovarian hormones, and response to gonadotropin stimulation. Fertility and sterility 89, 912–921.
| Evaluation of the relationship between follicular fluid oxidative stress, ovarian hormones, and response to gonadotropin stimulation.Crossref | GoogleScholarGoogle Scholar | 17681319PubMed |
Augustyniak, A., Bartosz, G., Čipak, A., Duburs, G., Horáková, L. U., Łuczaj, W., Majekova, M., Odysseos, A. D., Rackova, L., and Skrzydlewska, E. (2010). Natural and synthetic antioxidants: an updated overview. Free Radic. Res. 44, 1216–1262.
| Natural and synthetic antioxidants: an updated overview.Crossref | GoogleScholarGoogle Scholar | 20836663PubMed |
Bachmeier, B. E., Mirisola, V., Romeo, F., Generoso, L., Esposito, A., Dell’Eva, R., Blengio, F., Killian, P. H., Albini, A., and Pfeffer, U. (2010). Reference profile correlation reveals estrogen-like transcriptional activity of curcumin. Cell. Physiol. Biochem. 26, 471–482.
| Reference profile correlation reveals estrogen-like transcriptional activity of curcumin.Crossref | GoogleScholarGoogle Scholar | 20798532PubMed |
Behroozi-Lak, T., Ebrahimpour, M., Zarei, L., Pourjabali, M., Farhad, N., and Mohaddesi, H. (2018). Systemic administration of curcumin nanoparticles protects ischemia-reperfusion injury in ovaries: an animal model study. Rev. Assoc. Med. Bras. 64, 22–31.
| Systemic administration of curcumin nanoparticles protects ischemia-reperfusion injury in ovaries: an animal model study.Crossref | GoogleScholarGoogle Scholar | 29561939PubMed |
Bernal, A. B., Vickers, M. H., Hampton, M. B., Poynton, R. A., and Sloboda, D. M. (2010). Maternal undernutrition significantly impacts ovarian follicle number and increases ovarian oxidative stress in adult rat offspring. PLoS One 5, e15558.
| Maternal undernutrition significantly impacts ovarian follicle number and increases ovarian oxidative stress in adult rat offspring.Crossref | GoogleScholarGoogle Scholar | 21179452PubMed |
Borgeest, C., Symonds, D., Mayer, L., Hoyer, P., and Flaws, J. (2002). Methoxychlor may cause ovarian follicular atresia and proliferation of the ovarian epithelium in the mouse. Toxicol. Sci. 68, 473–478.
| Methoxychlor may cause ovarian follicular atresia and proliferation of the ovarian epithelium in the mouse.Crossref | GoogleScholarGoogle Scholar | 12151644PubMed |
Broekmans, F. J., Soules, M. R., and Fauser, B. C. (2009). Ovarian aging: mechanisms and clinical consequences. Endocr. Rev. 30, 465–493.
| Ovarian aging: mechanisms and clinical consequences.Crossref | GoogleScholarGoogle Scholar | 19589949PubMed |
Choe, C., Shin, Y.-W., Kim, E.-J., Cho, S.-R., Kim, H.-J., Choi, S.-H., Han, M.-H., Han, J., Son, D.-S., and Kang, D. (2010). Synergistic effects of glutathione and β-mercaptoethanol treatment during in vitro maturation of porcine oocytes on early embryonic development in a culture system supplemented with L-cysteine. J. Reprod. Dev. 56, 575–582.
| Synergistic effects of glutathione and β-mercaptoethanol treatment during in vitro maturation of porcine oocytes on early embryonic development in a culture system supplemented with L-cysteine.Crossref | GoogleScholarGoogle Scholar | 20657156PubMed |
Devine, P. J., Perreault, S. D., and Luderer, U. (2012). Roles of reactive oxygen species and antioxidants in ovarian toxicity. Biol. Reprod. 86, 27.
| Roles of reactive oxygen species and antioxidants in ovarian toxicity.Crossref | GoogleScholarGoogle Scholar | 22034525PubMed |
Diaz, F. J., O’Brien, M. J., Wigglesworth, K., and Eppig, J. J. (2006). The preantral granulosa cell to cumulus cell transition in the mouse ovary: development of competence to undergo expansion. Dev. Biol. 299, 91–104.
| The preantral granulosa cell to cumulus cell transition in the mouse ovary: development of competence to undergo expansion.Crossref | GoogleScholarGoogle Scholar | 16908014PubMed |
Djahanbakhch, O., Ezzati, M., and Zosmer, A. (2007). Reproductive ageing in women. J. Pathol. 211, 219–231.
| Reproductive ageing in women.Crossref | GoogleScholarGoogle Scholar | 17200943PubMed |
Eini, F., Novin, M. G., Joharchi, K., Hosseini, A., Nazarian, H., Piryaei, A., and Bidadkosh, A. (2017). Intracytoplasmic oxidative stress reverses epigenetic modifications in polycystic ovary syndrome. Reprod. Fertil. Dev. 29, 2313–2323.
| Intracytoplasmic oxidative stress reverses epigenetic modifications in polycystic ovary syndrome.Crossref | GoogleScholarGoogle Scholar | 28442024PubMed |
Faddy, M., and Gosden, R. (2007). Numbers of ovarian follicles and testing germ line renewal in the postnatal ovary: facts and fallacies. Cell Cycle 6, 1951–1952.
| Numbers of ovarian follicles and testing germ line renewal in the postnatal ovary: facts and fallacies.Crossref | GoogleScholarGoogle Scholar | 17660713PubMed |
Firmawati, A. (2018). Curcumin is effective in improving folliculogenesis profile and oocytes quality in vitro in ectopic endometriosis mouse (Mus musculus) models. Jurnal Ilmu-Ilmu Peternakan 28, 42–50.
| Curcumin is effective in improving folliculogenesis profile and oocytes quality in vitro in ectopic endometriosis mouse (Mus musculus) models.Crossref | GoogleScholarGoogle Scholar |
Geng, X., Hong, Q., Wang, W., Zheng, W., Li, O., Cai, G., Chen, X., and Wu, D. (2017). Biological membrane-packed mesenchymal stem cells treat acute kidney disease by ameliorating mitochondrial-related apoptosis. Sci. Rep. 7, 41136.
| Biological membrane-packed mesenchymal stem cells treat acute kidney disease by ameliorating mitochondrial-related apoptosis.Crossref | GoogleScholarGoogle Scholar | 28117405PubMed |
Hendarto, H., Widyanugraha, M. Y. A., and Widjiati, W. (2018). Curcumin improves growth factors expression of bovine cumulus-oocyte complexes cultured in peritoneal fluid of women with endometriosis. International Journal of Reproductive Biomedicine 16, 775–782.
| Curcumin improves growth factors expression of bovine cumulus-oocyte complexes cultured in peritoneal fluid of women with endometriosis.Crossref | GoogleScholarGoogle Scholar |
Liu, J., Liu, M., Ye, X., Liu, K., Huang, J., Wang, L., Ji, G., Liu, N., Tang, X., and Baltz, J. M. (2012). Delay in oocyte aging in mice by the antioxidant N-acetyl-L-cysteine (NAC). Hum. Reprod. 27, 1411–1420.
| Delay in oocyte aging in mice by the antioxidant N-acetyl-L-cysteine (NAC).Crossref | GoogleScholarGoogle Scholar | 22357770PubMed |
Ma, S., Shi, W., Wang, X., Song, P., and Zhong, X. (2017). Bisphenol A exposure during pregnancy alters the mortality and levels of reproductive hormones and genes in offspring mice. BioMed Res. Int. 2017, 3585809.
| Bisphenol A exposure during pregnancy alters the mortality and levels of reproductive hormones and genes in offspring mice.Crossref | GoogleScholarGoogle Scholar | 29181387PubMed |
McGraw, S., Robert, C., Massicotte, L., and Sirard, M.-A. (2003). Quantification of histone acetyltransferase and histone deacetylase transcripts during early bovine embryo development. Biol. Reprod. 68, 383–389.
| Quantification of histone acetyltransferase and histone deacetylase transcripts during early bovine embryo development.Crossref | GoogleScholarGoogle Scholar | 12533400PubMed |
Mehranjani, M. S., and Mansoori, T. (2016). Stereological study on the effect of vitamin C in preventing the adverse effects of bisphenol A on rat ovary. Int. J. Reprod. Biomed. (Yazd). 14, 403–410.
| Stereological study on the effect of vitamin C in preventing the adverse effects of bisphenol A on rat ovary.Crossref | GoogleScholarGoogle Scholar |
Melekoglu, R., Ciftci, O., Eraslan, S., Cetin, A., and Basak, N. (2018). Beneficial effects of curcumin and capsaicin on cyclophosphamide-induced premature ovarian failure in a rat model. J. Ovarian Res. 11, 33.
| Beneficial effects of curcumin and capsaicin on cyclophosphamide-induced premature ovarian failure in a rat model.Crossref | GoogleScholarGoogle Scholar | 29699594PubMed |
Noorafshan, A., and Ashkani-Esfahani, S. (2013). A review of therapeutic effects of curcumin. Curr. Pharm. Des. 19, 2032–2046.
| 23116311PubMed |
Noorafshan, A., Abdollahifar, M.-A., Karbalay-Doust, S., Asadi-Golshan, R., and Rashidian-Rashidabadi, A. (2013). Protective effects of curcumin and sertraline on the behavioral changes in chronic variable stress-induced rats. Exp. Neurobiol. 22, 96–106.
| Protective effects of curcumin and sertraline on the behavioral changes in chronic variable stress-induced rats.Crossref | GoogleScholarGoogle Scholar | 23833558PubMed |
Patzkó, Á., Bai, Y., Saporta, M. A., Katona, I., Wu, X., Vizzuso, D., Feltri, M. L., Wang, S., Dillon, L. M., and Kamholz, J. (2012). Curcumin derivatives promote Schwann cell differentiation and improve neuropathy in R98C CMT1B mice. Brain 135, 3551–3566.
| Curcumin derivatives promote Schwann cell differentiation and improve neuropathy in R98C CMT1B mice.Crossref | GoogleScholarGoogle Scholar | 23250879PubMed |
Paulose, T., Hannon, P. R., Peretz, J., Craig, Z. R., and Flaws, J. A. (2012). Estrogen receptor alpha overexpressing mouse antral follicles are sensitive to atresia induced by methoxychlor and its metabolites. Reprod. Toxicol. 33, 353–360.
| Estrogen receptor alpha overexpressing mouse antral follicles are sensitive to atresia induced by methoxychlor and its metabolites.Crossref | GoogleScholarGoogle Scholar | 22306526PubMed |
Qin, X., Cao, M., Lai, F., Yang, F., Ge, W., Zhang, X., Cheng, S., Sun, X., Qin, G., and Shen, W. (2015). Oxidative stress induced by zearalenone in porcine granulosa cells and its rescue by curcumin in vitro. PLoS One 10, e0127551.
| Oxidative stress induced by zearalenone in porcine granulosa cells and its rescue by curcumin in vitro.Crossref | GoogleScholarGoogle Scholar | 26658695PubMed |
Qin, C., Zhang, N., and Kallen, A. (2017). A novel, noncoding-RNA-mediated, post-transcriptional mechanism of AMH regulation by the H19/LET-7 axis. Fertil. Steril. 108, e25–e26.
| A novel, noncoding-RNA-mediated, post-transcriptional mechanism of AMH regulation by the H19/LET-7 axis.Crossref | GoogleScholarGoogle Scholar |
Reddy, P. S., Begum, N., Mutha, S., and Bakshi, V. (2016). Beneficial effect of curcumin in Letrozole induced polycystic ovary syndrome. Asian Pac. J. Reprod. 5, 116–122.
| Beneficial effect of curcumin in Letrozole induced polycystic ovary syndrome.Crossref | GoogleScholarGoogle Scholar |
Schefe, J. H., Lehmann, K. E., Buschmann, I. R., Unger, T., and Funke-Kaiser, H. (2006). Quantitative real-time RT-PCR data analysis: current concepts and the novel “gene expression’s C T difference” formula. J. Mol. Med. 84, 901–910.
| Quantitative real-time RT-PCR data analysis: current concepts and the novel “gene expression’s C T difference” formula.Crossref | GoogleScholarGoogle Scholar | 16972087PubMed |
Semba, R. D., Nicklett, E. J., and Ferrucci, L. (2010). Does accumulation of advanced glycation end products contribute to the aging phenotype? J. Gerontol. A Biol. Sci. Med. Sci. 65A, 963–975.
| Does accumulation of advanced glycation end products contribute to the aging phenotype?Crossref | GoogleScholarGoogle Scholar |
Stier, A., Reichert, S., Massemin, S., Bize, P., and Criscuolo, F. (2012). Constraint and cost of oxidative stress on reproduction: correlative evidence in laboratory mice and review of the literature. Front. Zool. 9, 37.
| Constraint and cost of oxidative stress on reproduction: correlative evidence in laboratory mice and review of the literature.Crossref | GoogleScholarGoogle Scholar | 23268929PubMed |
Şükür, Y. E., Kıvançlı, İ. B., and Özmen, B. (2014). Ovarian aging and premature ovarian failure. J. Turk. Ger. Gynecol. Assoc. 15, 190–196.
| Ovarian aging and premature ovarian failure.Crossref | GoogleScholarGoogle Scholar | 25317048PubMed |
Sun, R. Z., Lei, L., Cheng, L., Jin, Z. F., Zu, S. J., Shan, Z. Y., Wang, Z. D., Zhang, J. X., and Liu, Z. H. (2010). Expression of GDF-9, BMP-15 and their receptors in mammalian ovary follicles. J. Mol. Histol. 41, 325–332.
| Expression of GDF-9, BMP-15 and their receptors in mammalian ovary follicles.Crossref | GoogleScholarGoogle Scholar | 20857181PubMed |
Tarín, J., Ten, J., Vendrell, F. J., de Oliveira, M. N., and Cano, A. (1998). Effects of maternal ageing and dietary antioxidant supplementation on ovulation, fertilisation and embryo development in vitro in the mouse. Reprod. Nutr. Dev. 38, 499–508.
| Effects of maternal ageing and dietary antioxidant supplementation on ovulation, fertilisation and embryo development in vitro in the mouse.Crossref | GoogleScholarGoogle Scholar | 9923002PubMed |
Tatone, C., Amicarelli, F., Carbone, M. C., Monteleone, P., Caserta, D., Marci, R., Artini, P. G., Piomboni, P., and Focarelli, R. (2008). Cellular and molecular aspects of ovarian follicle ageing. Hum. Reprod. Update 14, 131–142.
| Cellular and molecular aspects of ovarian follicle ageing.Crossref | GoogleScholarGoogle Scholar | 18239135PubMed |
Tiwari-Pandey, R., and Ram Sairam, M. (2009). Modulation of ovarian structure and abdominal obesity in curcumin-and flutamide-treated aging FSH-R haploinsufficient mice. Reprod. Sci. 16, 539–550.
| Modulation of ovarian structure and abdominal obesity in curcumin-and flutamide-treated aging FSH-R haploinsufficient mice.Crossref | GoogleScholarGoogle Scholar | 19304795PubMed |
Ubaldi, F., and Rienzi, L. (2008). Morphological selection of gametes. Placenta 29, 115–120.
| Morphological selection of gametes.Crossref | GoogleScholarGoogle Scholar | 18762336PubMed |
Ueki, M., Ueno, M., Morishita, J., and Maekawa, N. (2013). Curcumin ameliorates cisplatin-induced nephrotoxicity by inhibiting renal inflammation in mice. J. Biosci. Bioeng. 115, 547–551.
| Curcumin ameliorates cisplatin-induced nephrotoxicity by inhibiting renal inflammation in mice.Crossref | GoogleScholarGoogle Scholar | 23245727PubMed |
Visser, J. A., de Jong, F. H., Laven, J. S., and Themmen, A. P. (2006). Anti-Müllerian hormone: a new marker for ovarian function. Reproduction 131, 1–9.
| Anti-Müllerian hormone: a new marker for ovarian function.Crossref | GoogleScholarGoogle Scholar | 16388003PubMed |
Wang, M.-E., Chen, Y.-C., Chen, I.-S., Hsieh, S.-C., Chen, S.-S., and Chiu, C.-H. (2012). Curcumin protects against thioacetamide-induced hepatic fibrosis by attenuating the inflammatory response and inducing apoptosis of damaged hepatocytes. J. Nutr. Biochem. 23, 1352–1366.
| Curcumin protects against thioacetamide-induced hepatic fibrosis by attenuating the inflammatory response and inducing apoptosis of damaged hepatocytes.Crossref | GoogleScholarGoogle Scholar | 22221674PubMed |
Xia, T., Fu, Y., Li, S., Ma, R., Zhao, Z., Wang, B., and Chao, C. (2016). Bu Shen Tiao Chong recipe restores diminished ovary reserve through the BDNF pathway. J. Assist. Reprod. Genet. 33, 795–805.
| Bu Shen Tiao Chong recipe restores diminished ovary reserve through the BDNF pathway.Crossref | GoogleScholarGoogle Scholar | 27094194PubMed |
Yan, Z., Dai, Y., Fu, H., Zheng, Y., Bao, D., Yin, Y., Chen, Q., Nie, X., Hao, Q., and Hou, D. (2018). Curcumin exerts a protective effect against premature ovarian failure in mice. J. Mol. Endocrinol. 60, 261–271.
| Curcumin exerts a protective effect against premature ovarian failure in mice.Crossref | GoogleScholarGoogle Scholar | 29437881PubMed |
Yang, Q., Dai, S., Luo, X., Zhu, J., Li, F., Liu, J., Yao, G., and Sun, Y. (2018). Melatonin attenuates postovulatory oocyte dysfunction by regulating SIRT1 expression. Reproduction 156, 81–92.
| Melatonin attenuates postovulatory oocyte dysfunction by regulating SIRT1 expression.Crossref | GoogleScholarGoogle Scholar | 29752296PubMed |
Zhang, T., Zhou, Y., Li, L., Wang, H.-H., Ma, X.-S., Qian, W.-P., Shen, W., Schatten, H., and Sun, Q.-Y. (2016). SIRT1, 2, 3 protect mouse oocytes from postovulatory aging. Aging (Albany NY) 8, 685–694.
| SIRT1, 2, 3 protect mouse oocytes from postovulatory aging.Crossref | GoogleScholarGoogle Scholar | 26974211PubMed |
