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Sara Ines Peña, Matias Alfonso Rubio, Constanza del Rosario Vargas, Constanza Francisca Alanis, and Alfonso Humberto Paredes

Leukaemia inhibitory factor (LIF) is a cytokine belonging to the IL-6 family that is important at the reproductive level in the uterine implantation process. However, there is very little evidence regarding its effect at the ovarian level. The aim of this work was to study the local involvement of the LIF/LIFRβ system in follicular development and steroidogenesis in rat ovaries. To carry out this research, LIF/LIFR/GP130 transcript and protein levels were measured in fertile and sub-fertile rat ovaries, and in vitro experiments were performed to assess STAT3 activation. Then, in in vivo experiments, LIF was administered chronically and locally for 28 days to the ovaries of rats by means of an osmotic minipump to enable us to evaluate the effect on folliculogenesis and steroidogenesis. It was determined by q-PCR and WB that LIF and its receptors are present in fertile and sub-fertile ovaries, and that LIF varies during the oestrous cycle, being higher during the oestrus and meta/dioestrus stages. In addition to this, it was found that LIF can activate STAT3 pathways and cause pSTAT3 formation. It was also observed that LIF decreases the number and size of preantral and antral follicles without altering the number of atretic antral follicles, and can increase the number of corpora lutea, with a notable increase in the levels of progesterone. It is therefore possible to infer that LIF exerts an important effect in vivo on folliculogenesis, ovulation and steroidogenesis, specifically the synthesis of progesterone.