Tumor Necrosis Factor α Enhances Oocyte/Follicle Apoptosis in the Neonatal Rat Ovary1

Abstract

Tumor necrosis factor alpha (TNFalpha) is a multifunctional cytokine present in oocytes and macrophages in the neonatal rat ovary. The presence of both TNFalpha 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 TNFalpha on isolated granulosa and theca cells and intact follicles; however, to our knowledge, this is the first study to investigate the effects of TNFalpha on the earliest stages of follicular development. Effects of TNFalpha 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 TNFalpha (0, 0.1, 1.0, 10, or 50 ng/ml), a function-blocking TNFalpha antibody (5 microg/ml), or control immunoglobulin (Ig) G. At 1 ng/ml, TNFalpha 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 TNFalpha 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 TNFalpha, apoptosis was examined by DNA laddering. At 1 ng/ml, TNFalpha 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 TNFalpha may be involved in oocyte atresia that normally occurs during the perinatal period.

Identification of a novel C1q family member in color crucian carp (Carassius auratus) ovary

“…One of them, TNFa, has been reported to express in human, mouse and rat oocytes on both mRNA and protein levels (Chen et al, 1993;Marcinkiewicz et al, 1994;Kondo et al, 1995;Naz et al, 1997). Marcinkiewicz et al (2002) and Morrison and Marcinkiewicz (2002) demonstrated that TNF could decrease oocyte and primordial follicle number through stimulation of oocyte apoptosis in rat ovary. Brannstrom et al (1995) observed that TNFa could promote ovulations of rat ovary.…”

Identification of a C1q family member associated with cortical granules and follicular cell apoptosis in Carassius auratus gibelio

“…and Morrison and Marcinkiewicz (2002) demonstrated that TNF could decrease oocyte and primordial follicle number through stimulation of oocyte apoptosis in rat ovary. Brannstrom et al (1995) observed that TNF-␣ could promote ovulation of rat ovary.…”

Expression of cytokine‐induced neutrophil chemoattractant suppresses tumor necrosis factor alpha expression and thereby prevents the follicles from undergoing atresia and apoptosis

“…The TNF alpha is an important element for follicular atresia and apoptosis 20, 28, 29. In this study, apoptosis by TUNEL staining and by the expression ratio of Bax and Bcl‐2 mRNAs was assessed.…”

“…In contrast to its effect on IL‐1 beta, the anti‐CINC/gro antibody induced an increase in TNF alpha expression, as compared to the control. These phenomena are related to a decrease in the ovulation rate and lead to follicular atresia and apoptosis 27, 28…”