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. 2017 Mar 28;8(13):20602-20611.
doi: 10.18632/oncotarget.15292.

Caffeine delays oocyte aging and maintains the quality of aged oocytes safely in mouse

Xia Zhang  1   2 , Xiaoyan Liu  1   3   4 , Li Chen  1   3 , Dan-Ya Wu  1   3 , Zheng-Wen Nie  1   3 , Ying-Ying Gao  1   3 , Yi-Liang Miao  1   3   2
Affiliations

Caffeine delays oocyte aging and maintains the quality of aged oocytes safely in mouse

Xia Zhang et al. Oncotarget. .

Abstract

Caffeine, as an oocyte aging inhibitor, was used in many different species to control or delay oocyte aging. However, the safety of caffeine and developmental competence of aged oocytes inhibited by caffeine has not been studied systematically. So we detected the spindle morphology, distribution of cortical granules, zona pellucida hardening and pronucleus formation to assess oocyte quality of caffeine treated oocytes. We found that aged oocytes treated by caffeine maintained weak susceptibility to activating stimuli and regained normal competent after aged further 6 hr. Caffeine maintained the spindle morphology, changed cortical granules distribution of aged oocytes and could not prevent zona pellucida hardening. Furthermore, caffeine increased pronucleus formation of aged oocytes and decreased fragmentation after fertilization. These results suggested that caffeine could maintain the quality of aged oocytes safely in mouse.

Keywords: Gerotarget; caffeine; mouse; oocyte aging; oocyte quality.

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Conflict of interest statement

CONFLICTS OF INTERESTS

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1. The effects of caffeine on the cumulus cells attaching and parthenogenetic activation during oocyte aging
A. Fresh oocytes with full cumulus cells attached. B. Caffeine-treated aged oocytes for 24 hr with most cumulus cells attached. C. Oocytes aged for 24 hr in vitro with few cumulus cells attached. D. The activation of fresh oocytes, caffeine treated oocytes and oocytes aged in vitro after parthenogenetic activation. All graphs show mean ± s.e.m. Abbreviations used in this and all subsequent figures: CA, caffeine treated; IVA, in vitro aging. a-c: Values without a common letter in their superscripts differ significantly (P < 0.05). The black arrows indicate the unattached cumulus cells in aged COCs. Bar, 80 μm.
Figure 2
Figure 2. The effects of caffeine on the spindle morphology during oocyte aging
A. Spindle morphology of fresh oocytes, caffeine-treated oocytes and oocytes aged in vitro. B. Percentage of oocytes with intact and abnormal spindles in fresh oocytes, caffeine-treated oocytes and oocytes aged in vitro. All graphs show mean ± s.e.m. Abbreviations used in this and all subsequent figures: CA, caffeine treated; IVA, in vitro aging. a-c: Values without a common letter in their superscripts differ significantly (P < 0.05). Spindle (green) and chromosomes (blue). The white arrows indicate the spindle defects and chromosome misalignment. Bar, 20 μm.
Figure 3
Figure 3. The effects of caffeine on the CGs distribution during oocyte aging
A. Four types of CGs distribution are shown in different oocytes. B. Percentage of oocytes with different CGs distribution in fresh oocytes, caffeine-treated oocytes and oocytes aged in vitro. All graphs show mean ± s.e.m. Abbreviations used in this and all subsequent figures: CA, caffeine treated; IVA, in vitro aging. a-c: Values without a common letter in their superscripts differ significantly (P < 0.05). CGs (green) and chromosomes (blue). The white arrow indicates CG free domain in fresh oocyte. Bar, 20 μm.
Figure 4
Figure 4. The effects of caffeine on the ZP hardening and fertilization by ICSI during oocyte aging
A. Changes in chymotrypsin digestion time of ZP (T50 is the time at which 50% of the ZPs per group were completely digested) of fresh oocytes, caffeine-treated oocytes and oocytes aged in vitro. B. The fertilization of fresh oocytes, caffeine treated oocytes and oocytes aged in vitro after Intracytoplasmic sperm injection (ICSI). Abbreviations used in this and all subsequent figures: CA, caffeine treated; IVA, in vitro aging. a-c: Values without a common letter in their superscripts differ significantly (P < 0.05).
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References

    1. Wang Q, Sun QY. Evaluation of oocyte quality: morphological, cellular and molecular predictors. Reproduction, fertility, and development. 2007;19:1–12. - PubMed
    1. Austin CR. In: In “concepts of development “. Whittaher J R, editor. Sinauer Associates Inc; 1974. Publisher.
    1. Ono T, Mizutani E, Li C, Yamagata K, Wakayama T. Offspring from intracytoplasmic sperm injection of aged mouse oocytes treated with caffeine or MG132. Genesis. 2011;49:460–471. - PubMed
    1. Goud P, Goud A, Van Oostveldt P, Van der Elst J, Dhont M. Fertilization abnormalities and pronucleus size asynchrony after intracytoplasmic sperm injection are related to oocyte postmaturity. Fertil Steril. 1999;72:245–252. - PubMed
    1. Kikuchi K, Izaike Y, Noguchi J, Furukawa T, Daen FP, Naito K, Toyoda Y. Decrease of histone H1 kinase activity in relation to parthenogenetic activation of pig follicular oocytes matured and aged in vitro. Journal of reproduction and fertility. 1995;105:325–330. - PubMed

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