Maternal contributions to pregnancy success: from gamete quality to uterine environment

Abstract

The establishment and maintenance of a pregnancy that goes to term is sine qua non for the long-term sustainability of dairy and beef cattle operations. The oocyte plays a critical role in providing the factors necessary for preimplantation embryonic development. Furthermore, the female, or maternal, environment where oocytes and embryos develop is crucial for the establishment and maintenance of a pregnancy to term. During folliculogenesis, the oocyte must sequentially acquire meiotic and developmental competence, which are the results of a series of molecular events preparing the highly specialized gamete to return to totipotency after fertilization. Given that folliculogenesis is a lengthy process in the cow, the occurrence of disease, metabolic imbalances, heat stress, or other adverse events can make it challenging to maintain oocyte quality. Following fertilization, the newly formed embryo must execute a tightly planned program that includes global DNA remodeling, activation of the embryonic genome, and cell fate decisions to form a blastocyst within a few days and cell divisions. The increasing use of assisted reproductive technologies creates an additional layer of complexity to ensure the highest oocyte and embryo quality given that in vitro systems do not faithfully recreate the physiological maternal environment. In this review, we discuss cellular and molecular factors and events known to be crucial for proper oocyte development and maturation, as well as adverse events that may negatively affect the oocyte; and the importance of the uterine environment, including signaling proteins in the maternal-embryonic interactions that ensure proper embryo development. We also discuss the impact of assisted reproductive technologies in oocyte and embryo quality and developmental potential, and considerations when looking into the prospects for developing systems that allow for in vitro gametogenesis as a tool for assisted reproduction in cattle.

Keywords: assisted reproduction; developmental competence; embryo; oocyte.

Figure 1. Follicular and embryonic events that are critical for a successful pregnancy. Oocytes are “stored” in the ovary enclosed in a layer of flat granulosa cells in the primordial follicles. Activation and growth of follicles through preantral stages takes several weeks to months, and during this time there is intense activity within the follicular unit with DNA replication, protein synthesis and transcriptional activity. Acquisition of meiotic competence by the oocyte occurs during the transition from late preantral to the early antral phase. Most of the transcripts that the oocyte will synthesize for later embryo use will be stored by the early to mid-antral stage. At this point the oocyte must also acquire developmental competence. Following fertilization of the mature oocyte by sperm, the embryo must now use the resources provided by the oocyte to ensure successful development to the blastocyst stage. Global epigenetic remodeling (with exception of imprinted genes) will be critical to reset the cellular program into a totipotent state. The embryonic genome activation (EGA) that occurs between the 4- and 16-cell stage is critical for the embryo to become transcriptionally autonomous and proceed to the first and second cell fate decisions at the blastocyst stage. There are many internal (e.g. metabolic state) and external (heat stress, in vitro culture) factors that can interfere with one or multiple events and disrupt oocyte and/or embryo development, resulting in failure to establish or maintain a pregnancy. Abbreviations: ICM: inner cell mass; TE: trophectoderm.