Skip to main content Accessibility help

Folic acid facilitates in vitro maturation of mouse and Xenopus laevis oocytes

  • Xiaoli Huang (a1) (a2), Shu Gao (a2), Wei Xia (a3), Shaoying Hou (a2) and Kun Wu (a2)...


The water-soluble B vitamins, folate and folic acid, play an important role in reproductive health, but little is known about the effects of folic acid on infertility. The present study tested the hypothesis that folic acid affects oocyte maturation, a possible cause of female infertility. We have studied the in vitro maturation of mouse and Xenopus oocytes. Hypoxanthine (Hx) was used as an inhibitor of mouse oocyte maturation to mimic in vivo conditions by maintaining high levels of cyclic-AMP. The frequency of first polar body (PB1) formation and germinal vesicle breakdown (GVBD) in mouse oocytes was decreased by Hx. This effect was counteracted by folic acid added to the medium. PB1 extrusion and GVBD percentages rose to 27·7 and 40·0 % from 12·8 and 19·9 %, respectively, by exposure to 500 μm-folic acid. Folic acid also restored the spindle configuration, which had been elongated by Hx, as well as normalising the distribution of cortical granules (CG). In folic acid-treated Xenopus eggs, extracellular signal-regulated kinase 1 was phosphorylated, cyclin B2 and Mos were up-regulated and the frequency of GVBD was accelerated. Taken together, the findings suggest that folic acid facilitates oocyte maturation by altering the expression and phosphorylation of proteins involved in M-phase-promoting factor and mitogen-activated protein kinase pathways, as well as causing changes in spindle configuration and CG migration.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Folic acid facilitates in vitro maturation of mouse and Xenopus laevis oocytes
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Folic acid facilitates in vitro maturation of mouse and Xenopus laevis oocytes
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Folic acid facilitates in vitro maturation of mouse and Xenopus laevis oocytes
      Available formats


Corresponding author

*Corresponding author: K. Wu, fax +86 451 8750 2885, email


Hide All
1Mrazek, M & Fulka, J Jr. (2003) Failure of oocyte maturation: possible mechanisms for oocyte maturation arrest. Hum Reprod 18, 22492252.
2Levran, D, Farhi, J, Nahum, H, et al. (2002) Maturation arrest of human oocytes as a cause of infertility: case report. Hum Reprod 17, 16041609.
3Marteil, G, Richard-Parpaillon, L & Kubiak, JZ (2009) Role of oocyte quality in meiotic maturation and embryonic development. Reprod Biol 9, 203224.
4Jamnongjit, M & Hammes, SR (2005) Oocyte maturation: the coming of age of a germ cell. Semin Reprod Med 23, 234241.
5Avazeri, N, Denys, A & Lefevre, B (2006) Lead cations affect the control of both meiosis arrest and meiosis resumption of the mouse oocyte in vitro at least via the PKC pathway. Biochimie 88, 18231829.
6Navarro, PA, Liu, L & Keefe, DL (2004) In vivo effects of arsenite on meiosis, preimplantation development, and apoptosis in the mouse. Biol Reprod 70, 980985.
7Tamura, T & Picciano, MF (2006) Folate and human reproduction. Am J Clin Nutr 83, 9931016.
8Wong, WY, Merkus, HM, Thomas, CM, et al. (2002) Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial. Fertil Steril 77, 491498.
9Lo, RS, Said, HM, Unger, TF, et al. (1991) An endogenous carrier-mediated uptake system for folate in oocytes of Xenopus laevis. Proc Biol Sci 246, 161165.
10Boxmeer, JC, Brouns, RM, Lindemans, J, et al. (2008) Preconception folic acid treatment affects the microenvironment of the maturing oocyte in humans. Fertil Steril 89, 17661770.
11Szymański, W & Kazdepka-Ziemińska, A (2003) Effect of homocysteine concentration in follicular fluid on a degree of oocyte maturity. Ginekol Pol 74, 13921396.
12Downs, SM (1997) Involvement of purine nucleotide synthetic pathways in gonadotropin-induced meiotic maturation in mouse cumulus cell-enclosed oocytes. Mol Reprod Dev 46, 155167.
13Ma, S, Lan, G, Miao, Y, et al. (2003) Hypoxanthine (HX) inhibition of in vitro meiotic resumption in goat oocytes. Mol Reprod Dev 66, 306313.
14Zhu, ZY, Chen, DY, Li, JS, et al. (2003) Rotation of meiotic spindle is controlled by microfilaments in mouse oocytes. Biol Reprod 68, 943946.
15Sanfins, A, Lee, GY, Plancha, CE, et al. (2003) Distinctions in meiotic spindle structure and assembly during in vitro and in vivo maturation of mouse oocytes. Biol Reprod 69, 20592067.
16Cau, J, Faure, S, Vigneron, S, et al. (2000) Regulation of Xenopus p21-activated kinase (X-PAK2) by Cdc42 and maturation-promoting factor controls Xenopus oocyte maturation. J Biol Chem 275, 23672375.
17Miyara, F, Aubriot, FX, Glissant, A, et al. (2003) Multiparameter analysis of human oocytes at metaphase II stage after IVF failure in non-male infertility. Hum Reprod 18, 14941503.
18Liu, M, Sims, D, Calarco, P, et al. (2003) Biochemical heterogeneity, migration, and pre-fertilization release of mouse oocyte cortical granules. Reprod Biol Endocrinol 1, 77.
19Mamo, S, Carter, F, Lonergan, P, et al. (2011) Sequential analysis of global gene expression profiles in immature and in vitro matured bovine oocytes: potential molecular markers of oocyte maturation. BMC Genomics 12, 151.
20Bilodeau-Goeseels, S (2006) Effects of culture media and energy sources on the inhibition of nuclear maturation in bovine oocytes. Theriogenology 66, 297306.
21Kang, MK & Han, SJ (2011) Post-transcriptional and post-translational regulation during mouse oocyte maturation. BMB Rep 44, 147157.
22Cooke, S, Tyler, JP & Driscoll, GL (2003) Meiotic spindle location and identification and its effect on embryonic cleavage plane and early development. Hum Reprod 18, 23972405.
23Choi, WJ, Banerjee, J, Falcone, T, et al. (2007) Oxidative stress and tumor necrosis factor-alpha-induced alterations in metaphase II mouse oocyte spindle structure. Fertil Steril 88, 12201231.
24Brunet, S & Maro, B (2005) Cytoskeleton and cell cycle control during meiotic maturation of the mouse oocyte: integrating time and space. Reproduction 130, 801811.
25Hegele-Hartung, C, Kuhnke, J, Lessl, M, et al. (1999) Nuclear and cytoplasmic maturation of mouse oocytes after treatment with synthetic meiosis-activating sterol in vitro. Biol Reprod 61, 13621372.
26Ju, JC, Jiang, S, Tseng, JK, et al. (2005) Heat shock reduces developmental competence and alters spindle configuration of bovine oocytes. Theriogenology 64, 16771689.
27Mandelbaum, J, Anastasiou, O, Levy, R, et al. (2004) Effects of cryopreservation on the meiotic spindle of human oocytes. Eur J Obstet Gynecol Reprod Biol 113, Suppl. 1, S17S23.
28Liu, RH, Sun, QY, Li, YH, et al. (2003) Effects of cooling on meiotic spindle structure and chromosome alignment within in vitro matured porcine oocytes. Mol Reprod Dev 65, 212218.
29Hou, SY, Zhang, L, Wu, K, et al. (2008) Thioglycolic acid inhibits mouse oocyte maturation and affects chromosomal arrangement and spindle configuration. Toxicol Ind Health 24, 227234.
30Trounson, A (2006) Spindle abnormalities in oocytes. Fertil Steril 85, 838(discussion 841).
31Connors, SA, Kanatsu-Shinohara, M, Schultz, RM, et al. (1998) Involvement of the cytoskeleton in the movement of cortical granules during oocyte maturation, and cortical granule anchoring in mouse eggs. Dev Biol 200, 103115.
32Liu, XY, Mal, SF, Miao, DQ, et al. (2005) Cortical granules behave differently in mouse oocytes matured under different conditions. Hum Reprod 20, 34023413.
33Zhang, DX, Park, WJ, Sun, SC, et al. (2011) Regulation of maternal gene expression by MEK/MAPK and MPF signaling in porcine oocytes during in vitro meiotic maturation. J Reprod Dev 57, 4956.
34Kotani, T & Yamashita, M (2002) Discrimination of the roles of MPF and MAP kinase in morphological changes that occur during oocyte maturation. Dev Biol 252, 271286.
35Lorca, T, Bernis, C, Vigneron, S, et al. (2010) Constant regulation of both the MPF amplification loop and the Greatwall-PP2A pathway is required for metaphase II arrest and correct entry into the first embryonic cell cycle. J Cell Sci 123, 22812291.
36Sadler, SE, Archer, MR & Spellman, KM (2008) Activation of the progesterone-signaling pathway by methyl-beta-cyclodextrin or steroid in Xenopus laevis oocytes involves release of 45-kDa Galphas. Dev Biol 322, 199207.



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed