Glutathione S-transferase theta 1 expressed in granulosa cells as a biomarker for oocyte quality in age-related infertility

Ito, Megumu; Muraki, Miho; Takahashi, Yuji; Imai, Misa; Tsukui, Tohru; Yamakawa, Naomi; Nakagawa, Koji; Ohgi, Shirei; Horikawa, Takashi; Iwasaki, Wakako; Iida, Ayumi; Nishi, Yoshihiro; Yanase, Toshihiko; Nawata, Hajime; Miyado, Kenji; Kono, Tomohiro; Hosoi, Yoshihiko; Saito, Hidekazu

doi:10.1016/j.fertnstert.2007.07.1389

« Previous Next »Fertility and Sterility
Volume 90, Issue 4 , Pages 1026-1035, October 2008

Glutathione S-transferase theta 1 expressed in granulosa cells as a biomarker for oocyte quality in age-related infertility

Megumu Ito, M.D.
- Division of Reproductive Medicine, Department of Perinatal Medicine and Maternal Care, National Center for Child Health and Development, Tokyo, Japan
Miho Muraki, B.S.
- Division of Reproductive Medicine, Department of Perinatal Medicine and Maternal Care, National Center for Child Health and Development, Tokyo, Japan
- Department of BioScience, Tokyo University of Agriculture, Tokyo, Japan
Yuji Takahashi, Ph.D.
- Division of Reproductive Medicine, Department of Perinatal Medicine and Maternal Care, National Center for Child Health and Development, Tokyo, Japan
- Reprint requests to: Yuji Takahashi, Ph.D., Division of Reproductive Medicine, Department of Perinatal Medicine and Maternal Care, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan (FAX: +81-3-3416-2222).
Misa Imai, M.S.
- Division of Reproductive Medicine, Department of Perinatal Medicine and Maternal Care, National Center for Child Health and Development, Tokyo, Japan
Tohru Tsukui, Ph.D.
- Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan
Naomi Yamakawa, Ph.D.
- Research Team for Geriatric Diseases, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
Koji Nakagawa, M.D.
- Division of Reproductive Medicine, Department of Perinatal Medicine and Maternal Care, National Center for Child Health and Development, Tokyo, Japan
Shirei Ohgi, M.D.
- Division of Reproductive Medicine, Department of Perinatal Medicine and Maternal Care, National Center for Child Health and Development, Tokyo, Japan
Takashi Horikawa, M.D.
- Division of Reproductive Medicine, Department of Perinatal Medicine and Maternal Care, National Center for Child Health and Development, Tokyo, Japan
Wakako Iwasaki, M.D.
- Division of Reproductive Medicine, Department of Perinatal Medicine and Maternal Care, National Center for Child Health and Development, Tokyo, Japan
Ayumi Iida, B.S.
- Division of Reproductive Medicine, Department of Perinatal Medicine and Maternal Care, National Center for Child Health and Development, Tokyo, Japan
Yoshihiro Nishi, M.D.
- Department of Physiology, Kurume University, Kurume, Japan
Toshihiko Yanase, M.D.
- Department of Medicine and Bioregulatory, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan
Hajime Nawata, M.D.
- Department of Medicine and Bioregulatory, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan
Kenji Miyado, Ph.D.
- Division of Reproductive Medicine, Department of Perinatal Medicine and Maternal Care, National Center for Child Health and Development, Tokyo, Japan
Tomohiro Kono, Ph.D.
- Department of BioScience, Tokyo University of Agriculture, Tokyo, Japan
Yoshihiko Hosoi, Ph.D.
- Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan
Hidekazu Saito, M.D.
- Division of Reproductive Medicine, Department of Perinatal Medicine and Maternal Care, National Center for Child Health and Development, Tokyo, Japan

Received 3 April 2007; received in revised form 6 July 2007; accepted 30 July 2007. published online 05 October 2007.

Objective

The goal of this study was to identify a reliable biomarker for age-related infertility.

Design

Laboratory study.

Setting

ART laboratory.

Patient(s)

Patients undergoing intracytoplasmic sperm injection or IVF cycles.

Intervention(s)

Expression of Glutathione S-transferase (GST) mRNA and protein in mural and cumulus granulosa cells obtained from infertile patients were examined by reverse transcriptase-polymerase chain reaction and immunofluorescence.

Main Outcome Measure(s)

Correlation between the expression of GST theta 1 (GSTT1) in granulosa cells and oocyte quality was a main outcome measure.

Result(s)

Expression of GSTT1 in granulosa cells from male factor patients was positively correlated with age and negatively with cumulus-oocyte complex maturity. When samples with high and low GSTT1 in granulosa cells were extracted from the other infertility factors, cumulus-oocyte complex maturity in the high GSTT1 group was significantly lower than that in the low GSTT1 group (high: 27.2% vs. low: 51.3%). The developmental capacity of oocytes in the high GSTT1 group was likely to be lower (high: 26.4% vs. low: 43.9%). Up-regulation of GSTT1 during aging may be promoted by FSH and H₂O₂, determined by an in vitro model.

Conclusion(s)

GSTT1 is a good indicator for age-related infertility.

Key Words: Glutathione S-transferase theta 1 (GSTT1), aging, granulosa cell, biomarker, oocyte quality

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M. Ito, M. Muraki, and Y. Takahashi contributed equally to this work.

Partly supported by a grant of Research on Child Health and Development (2005–2008) from the Ministry of Health, Labour and Welfare, and partly by grants (2005–2008: #17791147, #17791148; 2006–2009: #18591818) from the Ministry of Education, Culture, Sports, Science and Technology.

PII: S0015-0282(07)03046-4

doi:10.1016/j.fertnstert.2007.07.1389

« Previous Next »Fertility and Sterility
Volume 90, Issue 4 , Pages 1026-1035, October 2008

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