Abstract

The improvement of the embryo culture media is of high relevance due to its influence on successful implantation rates, pregnancy, neonatal outcomes, and potential effects in adult life. The ideal conditions for embryo development are those naturally occurring in the female reproductive tract, i.e., the oviductal and uterine fluids. To shed light on the differences between chemical and natural media, we performed the first comparative study of the low abundance proteins in plasma, uterine, and oviductal fluid collected, simultaneously, from healthy and fertile women that underwent a salpingectomy. The rationale for this design derives from the fact that high-abundant proteins in these fluids are usually those coming from blood serum and frequently mask the detection of low abundant proteins with a potentially significant role in specific processes related to the embryo–maternal interaction. The proteomic analysis by 1D-nano LC ESI-MSMS detected several proteins in higher amounts in oviductal fluid when compared to uterine and plasma samples (RL3, GSTA1, EZRI, DPYSL3, GARS, HSP90A). Such oviductal fluid proteins could be a target to improve fertilization rates and early embryo development if used in the culture media. In conclusion, this study presents a high-throughput analysis of female reproductive tract fluids and contributes to the knowledge of oviductal and uterine secretome.

Highlights

  • Assisted reproductive technologies (ART) have grown worldwide to assist the increasing number of patients who request these methods to conceive [1]

  • This study shows a proteomic characterization of the low abundance proteins in reproductive fluids that are significantly detected relative to the plasma of healthy, young, and fertile women during the secretory phase of the menstrual cycle

  • The present data corroborate that reproductive fluids represent an important source of biomarkers with potential interest in the development of better embryo culture media and that each one show particular proteomic profiles according to their roles in the different stages at the beginning of the life cycle

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Summary

Introduction

Assisted reproductive technologies (ART) have grown worldwide to assist the increasing number of patients who request these methods to conceive [1]. The outcomes considered in this study were the number of viable embryos grown, the rate of successful implantations, the pregnancy rates, and the birthweights of the newborns [15] Due to this uncertainty, it is imperative to invest more effort in the improvement of embryo culture conditions, trying to mimic the in vivo environment where embryos develop. Oviductal and uterine fluids (OF, UF) contain essential factors of different origin and composition that are pivotal for the development of gametes, zygotes, and later, embryos These include nutrients, hormonal and non-hormonal factors, electrolytes, and other macromolecules [16]. Human recombinant albumin is present in most IVF culture media This protein has been recognized for its important role in embryo culture and is the most abundant macromolecule in the human oviduct [20]. While the use of natural reproductive fluids in culture media may seem impractical at present, the inclusion of some of these proteins produced in the laboratory, such as recombinant albumin, may help to shorten the enormous distance between synthetic media and natural fluids, reducing the stress for the embryo

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