The involvement of tumor necrosis factor- alpha TNF as an intraovarian regulator of oocyte apoptosis in the neonatal rat

Abstract

Tumor necrosis factor-alpha (TNF) is a cytokine produced not only by various cells of the immune system, but also by various cells in the reproductive system. We have demonstrated that oocytes are an important source of TNF and that the onset of oocytic TNF expression occurs around birth. TNF receptors are localized on oocytes, granulosa cells and interstitial cells allowing for the possibility of autocrine or paracrine actions of TNF. The late fetal/early neonatal period represents a time during which several key events occur, including formation of the primordial follicle and extensive oocyte apoptosis. We have utilized an ovary culture system to examine the involvement of TNF in early ovarian function. This culture system allows both primordial follicle function and apoptosis to occur in vitro. Our results show that TNF can decrease oocyte and primordial follicle number through stimulation of oocyte apoptosis in vitro. TNF thus may serve as an important intraovarian factor involved in the determination of the size of the primordial follicle pool.

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.…”

Interactions between progesterone and tumor necrosis factor-α in the regulation of primordial follicle assembly

“…In the present study, TNFa treatment of cultured ovaries does not change the rate or percentage of assembled follicles compared with controls. In earlier work by Marcinkiewicz & Balchak (2002), treatment of cultured rat ovaries with TNFa resulted in a reduction in both the number of unassembled oocytes and the number of oocytes assembled into primordial follicles in the ovary. Since both the number of assembled and unassembled oocytes decreased in treated ovaries, the percentage of assembled follicles was similar in treated compared with the control ovaries.…”

“…Previous literature suggests that estrogen is another steroid hormone important for follicle assembly in the mouse (Jefferson & Newbold 2006, Pepe & Billiar 2006, rat (Kezele & Skinner 2003), and baboon (Pepe & Billiar 2006), but estrogen likely plays a greater role in arresting the primordial follicle in the primordial stage and not allowing the primordial to primary follicle transition (Kezele & Skinner 2003). TNFa has been implicated as a growth factor that promotes the oocyte apoptosis thought to be necessary for follicle assembly to occur (Chen & Marcinkiewicz 1993, Marcinkiewicz & Krishna 1994, Kondo & Maruo 1995, Marcinkiewicz & Balchak 2002. In the present study, TNFa treatment of cultured ovaries does not change the rate or percentage of assembled follicles compared with controls.…”

“…Ovaries were randomly assigned to treatment groups with two to three ovaries per floating filter in each well. Treatments during organ culture included recombinant rat tumor necrosis factor-a (TNFa) (R&D Systems, Inc., Minneapolis, MN, USA) at 1 ng/ml, which was a dose found to be effective in inducing the oocyte apoptosis that accompanies follicle assembly (Marcinkiewicz & Balchak 2002). Some ovaries were treated with progesterone (P 4 ) (Sigma) at 10 K6 M. The medium was supplemented with penicillin and streptomycin to prevent bacterial contamination.…”

“…The surviving oocytes become surrounded by pregranulosa cells to form primordial follicles. Studies have shown that ovaries and oocytes express tumor necrosis factor-a (TNFa) at the time of follicular assembly in rodents, and TNFa treatment can increase oocyte apoptosis (Chen & Marcinkiewicz 1993, Marcinkiewicz & Krishna 1994, Kondo & Maruo 1995, Marcinkiewicz & Balchak 2002. Observations suggest that TNFa is a stimulator of oocyte apoptosis that leads to oocyte nest breakdown and promotes assembly of primordial follicles.…”