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Reproductive Aging is Associated With Altered Gene Expression in Human Luteinized Granulosa Cells

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Abstract

Declining reproductive success with aging is attributable to qualitative and quantitative deterioration in oocytes, which are nurtured by granulosa cells (GCs). This prospective study assesses whether reproductive aging is accompanied by differential gene expression in luteinized GCs from in vitro fertilization (IVF) patients. Women with nonovarian infertility etiologies were categorized as younger (≤30, n = 3) or older (≥40, n = 3). During oocyte retrieval, mural GCs were isolated; messenger RNA (mRNA) was extracted and transcribed for complementary DNA (cDNA) microarray analysis. Differential gene expression was confirmed by real-time polymerase chain reaction (PCR). Analysis revealed 120 genes were differentially expressed. Three genes were upregulated and 117 were downre-gulated (including interleukin [IL]-1β, IL-1R2, and IL-6R) in GCs of older versus younger patients. Our data provide evidence of downregulation in IL-1 and IL-6 gene families in luteinized GCs with advancing age. Given previously recognized roles for the IL gene family in folliculogenesis and ovulation, our findings may partly explain ovulatory and luteal dysfunctions associated with reproductive aging.

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Authors and Affiliations

  1. Reproductive Medicine Associates of Connecticut, Norwalk, Connecticut, USA

    Joshua M. Hurwitz MD

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

    Joshua M. Hurwitz MD, Sangita Jindal PhD & Nanette Santoro MD

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

    Sangita Jindal PhD, Dara Berger PhD & Nanette Santoro MD

  4. The Institute for Reproductive Medicine and Science at St Barnabas, Livingston, New Jersey, USA

    Keri Greenseid MD

  5. Environmental and Occupational Health Science Institute, Robert Wood Johnson Medical School, Piscataway, New Jersey, USA

    Andrew Brooks PhD

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

    Lubna Pal MBBS

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  1. Joshua M. Hurwitz MD
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  2. Sangita Jindal PhD
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Correspondence to Sangita Jindal PhD.

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Hurwitz, J.M., Jindal, S., Greenseid, K. et al. Reproductive Aging is Associated With Altered Gene Expression in Human Luteinized Granulosa Cells. Reprod. Sci. 17, 56–67 (2010). https://doi.org/10.1177/1933719109348028

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