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1 February 2002 Tumor Necrosis Factor α Enhances Oocyte/Follicle Apoptosis in the Neonatal Rat Ovary
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Tumor necrosis factor α (TNFα) is a multifunctional cytokine present in oocytes and macrophages in the neonatal rat ovary. The presence of both TNFα and its receptors in the neonatal rat ovary suggests a potential role for it in follicle assembly or oocyte atresia. Previous studies have provided support for effects of TNFα on isolated granulosa and theca cells and intact follicles; however, to our knowledge, this is the first study to investigate the effects of TNFα on the earliest stages of follicular development. Effects of TNFα on oocyte/follicle number and apoptosis were investigated using an ovarian organ-culture system that supported assembly of primordial follicles in vitro. Ovaries were collected on the day of birth and treated with TNFα (0, 0.1, 1.0, 10, or 50 ng/ml), a function-blocking TNFα antibody (5 μg/ml), or control immunoglobulin (Ig) G. At 1 ng/ml, TNFα decreased follicle and oocyte numbers during 3 days of culture, whereas higher (10 and 50 ng/ml) or lower (0.1 ng/ml) doses had no effect. Treatment with TNFα antibodies increased the number of oocytes and follicles compared to nonspecific IgG control. To determine whether the decreased oocyte/follicle numbers were due to an apoptotic effect of TNFα, apoptosis was examined by DNA laddering. At 1 ng/ml, TNFα increased apoptotic DNA laddering twofold, with no significant effect from lower or higher doses. The cells undergoing apoptosis, as determined by in situ end-labeling, were oocytes, interstitial cells, and granulosa cells. These findings suggest that TNFα may be involved in oocyte atresia that normally occurs during the perinatal period.

Leisa J. Morrison and Jennifer L. Marcinkiewicz "Tumor Necrosis Factor α Enhances Oocyte/Follicle Apoptosis in the Neonatal Rat Ovary," Biology of Reproduction 66(2), 450-457, (1 February 2002).
Published: 1 February 2002

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