Human Reproduction, Vol 12, 1233-1239, Copyright © 1997 by Oxford University Press
A Arici, E Oral, O Bahtiyar, O Engin, E Seli and EE Jones
Leukaemia inhibitory factor (LIF) is a 43 kDa glycoprotein with a
remarkable range of biological actions in different tissue systems. LIF
improves the rate of fertilization of mouse oocytes in vitro and up-
regulates aromatase enzyme. We postulated that LIF may be an important
modulator of ovarian function and may also improve embryo quality in
humans. Follicular fluid samples from patients undergoing in-vitro
fertilization (IVF) and embryo transfer (n = 123), from women undergoing
ovarian stimulation (n = 4) and from women undergoing laparoscopy for tubal
ligation during their follicular phase (n = 3) were used. Follicular fluid
LIF, oestradiol, and progesterone were measured and embryo quality was
assessed. Granulosa-lutein cells were cultured for 3 days in Ham's
F-12:Dulbecco's modified Eagle's medium (DMEM). Ovarian stromal cells,
isolated by enzymatic dispersion of ovarian tissue, were also cultured in
the same medium. Following experimental treatments, LIF mRNA and protein
concentrations were quantified. The concentration of LIF was 0.8 +/- 0.3
(mean +/- SEM) pg/ml in pre-human chorionic gonadotrophin (HCG) follicular
fluid samples and 13.0 +/- 1.1 pg/ml in post-HCG follicular fluid samples
(P < 0.05). LIF levels were undetectable in three follicular fluid
samples obtained during unstimulated follicular phase. There was a
correlation between follicular fluid LIF and follicular fluid oestradiol
concentrations (r = 0.36; P = 0.0001) and the number of grade I embryos (r
= 0.62; P = 0.01). LIF mRNA and the protein were expressed constitutively
but in low amounts in the ovarian stromal cell cultures. The concentrations
of LIF mRNA as well as protein were increased by interleukin (IL)-1alpha
and tumour necrosis factor alpha (TNF alpha) in a time- and
concentration-dependent manner. Purified granulosa-lutein cells expressed
low amounts of LIF mRNA and protein which were not significantly increased
by IL-1alpha or TNF alpha. Our findings suggest that HCG stimulates the
expression of LIF in follicular fluid. Both granulosa-lutein and ovarian
stromal cells express the LIF mRNA and produce the protein. Modulation of
LIF in these cells may play an important role in the physiology of
ovulation and early embryo development.
ARTICLES
Leukaemia inhibitory factor expression in human follicular fluid and ovarian cells
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520-8063, USA.
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