The effect of leukemia inhibitory factor (LIF) on trophoblast differentiation: a potential role in human implantation
MJ Nachtigall, HJ Kliman, RF Feinberg, DL Olive, O Engin and A Arici
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Leukemia inhibitory factor (LIF) is a multifunctional glycoprotein strongly
associated with normal implantation in the mouse. We have recently
determined that LIF is expressed in the human endometrium in a menstrual
cycle dependent manner. Maximal expression is observed between days 19 and
25 of the menstrual cycle, coinciding with the time of human implantation.
In this study we have utilized purified cultures of human cytotrophoblasts
to examine the effects of LIF on several morphologic and biochemical
markers of the trophoblastic differentiation. We purified human
cytotrophoblasts from term placentae and cultured them with and without LIF
(10 ng/mL). The secretion of human CG, oncofetal fibronectin, and
progesterone were measured at 24, 48, 72, and 96 h. Northern blot analysis
was used to assess messenger RNA (mRNA) expression of beta hCG and
oncofetal fibronectin. We found that LIF markedly decreased trophoblast
production of hCG protein at 72 and 96 h, as well as expression of beta hCG
mRNA. LIF also significantly increased the expression of oncofetal
fibronectin mRNA and secretion of the protein. LIF did not affect
steroidogenic activity of cultured trophoblasts, as determined by
progesterone production. These biochemical changes are characteristic of
cytotrophoblast differentiation toward an anchoring extravillous phenotype.
Thus, LIF appears to be an important regulator of human embryonic
implantation by directly modulating trophoblast differentiation.
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