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Impaired Gremlin 1 (GREM1) expression in cumulus cells in young women with diminished ovarian reserve (DOR)

  • Gonad Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

A symbiotic relationship between ovarian granulosa cells (GC) and the developing oocyte is critical. Genetic modulations in GC’s can lead to reproductive insufficiency, highlighting the role of GC’s in reproductive competence. Utilizing gene expression analyses in cumulus GC’s, we attempt to enhance our understanding of mechanisms that may contribute to poor reproductive capacity in young women with diminished ovarian reserve (DOR).

Methods

We measured gremlin 1 (GREM1) gene expression in GC’s from infertile women <38 years undergoing in vitro fertilization in the context of DOR.

Results

GREM1, a member of the differential screening-selected gene aberrative in neuroblastoma (DAN) family of genes known for its highly regulated expression pattern during folliculogenesis and a downstream effecter of oocyte-derived growth and differentiation factor 9, was down-regulated 3-fold (−3.08) in women with DOR versus control; down-regulation was confirmed by qRT-PCR (−4.02).

Conclusion

This is the first demonstration linking differential expression of Gremlin with etiology of infertility in women.

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Acknowledgements

The authors would like to acknowledge the invaluable contributions of Dr. Andrew Brooks in microarray and RT-PCR interpretation, and Joshua Hurwitz MD, Athena Zapantis BS, and Michael Nihsen MS for technical assistance.

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Authors and Affiliations

  1. Division of Reproductive Endocrinology & Infertility, Department of Obstetrics, Gynecology & Women’s Health, Albert Einstein College of Medicine, Bronx, NY, USA

    Sangita Jindal

  2. Montefiore’s Institute for Reproductive Medicine and Health, 141 South Central Ave, Suite 201, Hartsdale, NY, 10530, USA

    Sangita Jindal & Dara Berger

  3. The Institute for Reproductive Medicine and Science at St. Barnabas, Livingston, NJ, USA

    Keri Greenseid

  4. Department of Obstetrics & Gynecology, University of Colorado at Denver, Aurora, CO, USA

    Nanette Santoro

  5. Division of Reproductive Endocrinology & Infertility, Department Of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA

    Lubna Pal

Authors
  1. Sangita Jindal
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  2. Keri Greenseid
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  3. Dara Berger
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  4. Nanette Santoro
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  5. Lubna Pal
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Corresponding author

Correspondence to Sangita Jindal.

Additional information

All research was performed in the Division of REI, Department of Obstetrics, Gynecology & Women’s Health, Albert Einstein College of Medicine, Bronx, NY and Montefiore’s Institute for Reproductive Medicine and Health, Hartsdale, NY. A portion of this work was presented at the Annual Meeting of the Society for Gynecologic Investigation, March 2008.

Financial Support

This investigation was supported by grants from Ferring Pharmaceuticals, Inc (to SJ) and NIH grants 5K12 RR17672 (to LP) and K24 CD41978 (to NS).

Capsule Gremlin 1 expression is impaired in cumulus granulosa cells of young women with diminished ovarian reserve (DOR), suggesting a possible mechanism for the ovarian dysfunction associated with DOR.

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Jindal, S., Greenseid, K., Berger, D. et al. Impaired Gremlin 1 (GREM1) expression in cumulus cells in young women with diminished ovarian reserve (DOR). J Assist Reprod Genet 29, 159–162 (2012). https://doi.org/10.1007/s10815-011-9684-8

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  • DOI: https://doi.org/10.1007/s10815-011-9684-8

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