PARENT SESSION
Follicular Development

ROLE OF LEUKEMIA INHIBITORY FACTOR (LIF) IN INITIATING PRIMORDIAL FOLLICLE DEVELOPMENT AND FOLLICULOGENESIS.

Nilsson, Eric¹, Sadler-Riggleman, Ingrid ¹, Kezele, Phillip¹, Skinner, Michael¹, ¹

ABSTRACT- Mammalian ovaries after birth contain a large cohort of primordial follicles. As growth and maturation occurs some primordial follicles are stimulated to initiate follicle development and begin folliculogenesis. Kit ligand (KL) has previously been shown to promote primordial follicle development and folliculogenesis and to promote proliferation of theca and stromal cells. Similarly, basic fibroblast growth factor (bFGF) has been shown to promote primordial follicle development and folliculogenesis including growth of granulosa and theca cells. Leukemia inhibitory factor (LIF) is a cytokine paracrine signaling molecule produced by granulosa cells and found in follicular fluid of late stage follicles. LIF also has a role in the developing ovary regulating primordial germ cell function. The present studies investigate the potential role of LIF to initiate folliculogenesis by promoting the development of primordial follicles in a rat ovary organ culture model. Ovaries were dissected from four-day-old rats and placed into a floating filter culture system where they received treatments and were cultured for 14 days. Ovaries treated with LIF (50ng/mL) had 15% more developing follicles compared to untreated cultured ovaries. This shows that LIF stimulated a larger proportion of primordial follicles to begin development. Ovaries treated with a neutralizing antibody to LIF exhibited a 5% decrease in the proportion of developing follicles compared to untreated controls. This indicates that neutralizing endogenously produced LIF inhibited slightly the spontaneous primordial follicle development seen in untreated cultured ovaries. LIF did not induce proliferation in bovine granulosa or theca cell cultures. Interestingly treatment of granulosa cells with LIF induced a more than two-fold increase in KL mRNA expression. In summary, these data indicate that LIF does have a role in initiating primordial follicle development, either alone or through interactions with other growth factors such as KL and/or bFGF. How LIF, KL and bFGF interact to regulate follicle development is currently under investigation.

KEY WORDS: ovary, follicular development, leukaemia inhibitory factor, rat