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Role of Progesterone Receptor Membrane Component-1 in oogenesis and mammalian fertility

Final Report Summary - PRO-OVUM (Role of Progesterone Receptor Membrane Component-1 in oogenesis and mammalian fertility)

The scientific aim of the present project is to test the hypothesis that Progesterone Receptor Membrane Component 1 (PGRMC1) is one of the key factors that regulate mammalian oocyte quality and therefore female fertility. This hypothesis is based on preliminary data in bovine oocytes that suggest that PGRMC1 is likely to play an essential role in chromosomal segregation, which occurs during oocyte maturation. In fact, our previous studies show that PGRMC1 localizes to the centromeric region of the chromosomes at metaphase I and II stages of meiosis I, while it concentrates between the separating chromosomes at anaphase I and telophase I stages. Moreover, the injection of an antibody to PGRMC1 significantly suppressed the percentage of bovine oocytes that successfully complete meiosis.
In the first two years of the project, mechanistic studies using advanced technologies, such as oocyte micromanipulation and small interfering mediated gene silencing, confirmed our hypothesis and suggested a new function for PGRMC1 in mediating cytokinesis that leads to polar body emission. The studies conducted during the second period of the project add new insights into PGRMC1 function, confirming a role in late stages of cell division, which seems to be conserved in both oocyte meiosis and bovine granulosa (ovarian) cells mitosis. Furthermore, we have started to dissect the mechanisms by which PGRMC1-AURKB interaction is involved in proper cell division. These findings are fundamental advancements beyond the state of the art: not only we have added new knowledge on the biology of the oocyte by demonstrating that PGRMC1 regulate the ability of bovine oocytes to complete meiotic maturation, but have also provided compelling evidence that PGRMC1 regulates bovine granulosa cells growth. This is relevant in the reproductive biology field, since implies that PGRMC1 plays a role in follicular development, which is pivotal in female fertility.
The implementation of the scientific project has led to the establishment new collaborations and skills in the Reproductive and Developmental Biology Laboratory (RedBio Lab, www.redbiolab.unimi.it) of the University of Milan, which is in turn contributing to improve the attractiveness of the lab itself and of the Host Institution. Dr Valentina Lodde, the Marie Curie Fellow involved in the project, has reached a good level of independence, which will contribute substantially to her career development at the University of Milan.
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