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Abstract: The dialog between oocyte and cumulus cells brings a major contribution for oocyte meiotic and developmental competence. On the one hand, the oocyte will modulate follicle growth through specific gene expression (Figα, GDF-9, BMP15) as well as its meiosis (GPR3 et PDE3A). Beyond its action on proliferation, oocyte will control in part the differentiation of cumulus cells with a particular involvement of GDF-9, BMP15 in this late maturation process. On the other hand, somatic cells are the main targets of gonadotropins and will modulate both oocyte growth and maturation. Gap-junctions between oocyte and cumulus cells have a major role in this interaction, since they allow the action of some oocyte specific genes (GDF9) but also the control of its own metabolism and calcium movements. While ovulation will involve gonadotropins action on somatic cells, EGF-like factors recruited at the cumulus level will participate in this process. Finally we may suspect that improving the knowledge on oocyte–cumulus dialog will contribute to better define oocyte competence, while bringing some clues for in vitro maturation. [Copyright &y& Elsevier]

STUDY QUESTION Does BCAR4 have a role in mammalian embryo development? SUMMARY ANSWER Expression, localization and functional data support that BCAR4 is a maternal-effect protein in non-rodent mammals. WHAT IS KNOWN ALREADY BCAR4 was previously identified as an oocyte-specific gene in cattle, and as a marker of certain breast tumors in humans. STUDY DESIGN, SIZE, DURATION Human oocytes were obtained from patients undergoing IVF, but had failed to mature after ovarian stimulation. Dog oocytes were obtained from ovariectomized bitches. Pig, horse and bovine ovaries were obtained from commercial slaughterhouses for extraction of immature oocyte–cumulus complexes. In vivo matured bovine matured oocytes were obtained after ovulation induction and ovulation inducing treatment of Montbeliard heifers. MATERIALS, SETTING AND METHODS Expression at the RNA level was analyzed by reverse transcription coupled to polymerase chain reaction. Western blot and immunolabeling coupled to confocal or electronic microscopy were used to analyze bovine protein expression and intracellular localization. For the functional approach, short-interfering RNA were microinjected into mature bovine oocytes, followed by IVF; cleavage and embryo development were recorded. MAIN RESULTS AND THE ROLE OF CHANCE The BCAR4 gene is conserved in mammalian species from various orders and has been lost in rodents after divergence with lagomorphs. The transcript is expressed in the oocytes of humans and domestic species. We bring the first experimental evidence of the BCAR4 protein in mammals. In cattle, the protein is not detected in immature oocytes but starts to be synthesized during maturation, increases in the zygote and persists until the morula stage. The protein is detected throughout the cytoplasm in mature oocytes, concentrates in and around the pronuclei in the zygote, and appears to shuttle in and out of the nuclei starting in the 2-cell embryo; BCAR4 is also present at the junctions between blastomeres from 2-cell to morula. In our functional approach, targeting the BCAR4 transcript by small-interfering RNA significantly compromised development to the morula or/and blastocyst stages (P < 0.05, logistic regression). LIMITATIONS, REASONS FOR CAUTION As indicated above, protein expression and function were investigated in cattle and mostly in vitro matured oocytes were used. WIDER IMPLICATIONS OF THE FINDINGS This study provides a novel candidate gene whose mutation or deregulation may underlie certain cases of unexplained female infertility. STUDY FUNDING/COMPETING INTEREST(S) This work was sponsored by grants from the French Ministry of Research (#03P409), Agence Nationale de la Recherche (#ANR-07-GANI-004-01) and Apisgene. No competing interests declared. [ABSTRACT FROM AUTHOR]

Abstract: Preimplantation embryo development is one of the key features with implantation itself to achieve a pregnancy. Assisted Reproductive Technologies both in human and animal have improved our knowledge on these events, although it remains elusive to predict embryo potential to give a baby. Among various ways to define embryo viability, noninvasive approaches get a serious advantage linked to the final transfer of the embryo. Techniques devoted to characterize the embryo secretome using proteomic or metabolomic approaches may be non invasive. Based on a direct identification of products of the embryo metabolism or an assessment of profile(s) related with embryo viability, they have greatly improved their sensitivity to allow their use in clinical embryology, once validated. Oocyte-cumulus dialogue, as a key factor for oocyte competence to meiosis and embryo development, was particularly concerned with both genomic and proteomic assessment of cumulus cells. While it is not possible to designate at the time being which among these approaches will be robust and cost-efficient enough to help routinely the clinical embryologist in assisted reproductive techniques (ART), one can predict that our ability to select the “right” embryo will combine morphological criteria already available with validated biomarkers. [Copyright &y& Elsevier]