Intra-follicular interactions affecting mammalian oocyte maturation

Abstract

Nuclear oocyte maturation is defined as reinitiation and progression of the first meiotic division and subsequently formation of the methaphase II (MII) plate. Concomitantly with nuclear maturation, cytoplasmic maturation which is essential for proper fertilization and early embryo development is completed. The trigger for resumption of meiosis in vivo is considered to be the preovulatory surge of luteinizing hormone (LH), whereas oocytes removed from their follicle spontaneously resume meiosis in vitro and mature up to the MII stage. For oocyte collection in women, ovarian stimulation protocols involve gonadotrophin-releasing hormone agonists or antagonists in combination with gonadotrophins to generate multiple follicles in the ovary containing in vivo matured oocytes. Recovery of immature oocytes followed by in vitro maturation of these oocytes is an attractive alternative for this comprehensive stimulation protocol. Although maturation in vitro can be accomplished in human oocytes, like in cattle it is associated with reduced developmental competence. Fundamental studies on the process of maturation in vitro as well as in vivo may therefore ameliorate culture conditions for the maturation of oocytes in vitro. The data presented in chapter 2, 3 and 4 of this thesis confirm the important role of granulosa and theca cells in preventing spontaneous or gonadotrophin triggered resumption of meiosis in bovine oocytes originating from small and medium sized follicles. This knowledge can contribute to the design of two-step culture systems leading to improved conditions during final oocyte maturation. Already since the 1950s there are reports about disrupted reproduction functions after severe changes in energy balance resulting in suboptimal body conditions. At present it has been recognized that dairy cows experience reduced fertility when nutrient requirements for maintenance and lactation exceed nutrient intake. Moreover, in women undergoing IVF treatment both overweight and underweight lead to decreased chances of pregnancy. Selection for the trait of milk production and the associated reduced fertility in the modern dairy cow and the alarming increase in the proportion of obese women are two examples that demonstrate the demand for research on pathways linking energy balance and reproduction. Data presented in chapter 5 and 6 of this thesis concerning the role of leptin, one of the factors connecting energy balance and reproduction, in oocyte maturation and subsequent embryo production point to an enhancing effect of leptin on oocyte maturation. However high leptin levels in follicular fluid from patients at the day of oocyte retrieval are related to a lower chance on pregnancy. Considering this discrepancy, further studies on the role of leptin in reproduction should focus on early embryonic development and implantation. In general the studies presented in this thesis provide more insights on the fundamental mechanisms regulating mammalian oocyte maturation with potential for development of improved methods of embryo production in vitro or for assisted reproduction applications in livestock and humans.