Fuller W. Bazer

Discovery of candidate genes and pathways in the endometrium regulating ovine blastocyst growth and conceptus elongation

Establishment of pregnancy in ruminants requires blastocyst growth to form an elongated conceptus that produces interferon tau, the pregnancy recognition signal, and initiates implantation. Blastocyst growth and development requires secretions from the uterine endometrium. An early increase in circulating concentrations of progesterone (P4) stimulates blastocyst growth and elongation in ruminants. This study utilized sheep as a model to identify candidate genes and regulatory networks in the endometrium that govern preimplantation blastocyst growth and development. Ewes were treated daily with either P4 or corn oil vehicle from day 1.5 after mating to either day 9 or day 12 of pregnancy when endometrium was obtained by hysterectomy. Microarray analyses revealed many differentially expressed genes in the endometria affected by day of pregnancy and early P4 treatment. In situ hybridization analyses revealed that many differentially expressed genes were expressed in a cell-specific manner within the endometrium. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to identify functional groups of genes and biological processes in the endometrium that are associated with growth and development of preimplantation blastocysts. Notably, biological processes affected by day of pregnancy and/or early P4 treatment included lipid biosynthesis and metabolism, angiogenesis, transport, extracellular space, defense and inflammatory response, proteolysis, amino acid transport and metabolism, and hormone metabolism. This transcriptomic data provides novel insights into the biology of endometrial function and preimplantation blastocyst growth and development in sheep.

Endocrinology of the Transition from Recurring Estrous Cycles to Establishment of Pregnancy in Subprimate Mammals

Pregnancy is established and maintained in subprimate mammals in response to a series of interactions among the conceptus (embryo and associated membranes), uterus, and/or ovarian corpus luteum (CL). These interactions prevent functional and structural regression of the CL, or luteolysis. This chapter describes aspects of the endocrinology of recurring estrous cycles in ruminants, swine, horses, cats, dogs, and rodents, but the primary focus is on signaling for maternal recognition of pregnancy. During the peri-implantation period, pregnancy recognition signals from the conceptus to the maternal system are anti-luteolytic and/or luteotrophic. The functional life-span of the CL is controlled by release of prostaglandin F2α (PGF) from the uterus and/or ovaries, whereas pregnancy recognition signals from the trophoblast may act in a paracrine or endocrine manner to interrupt endometrial or intraovarian production of luteolytic PGF (antiluteolytic) or the effect may be directly on the CL (luteotropic). The primary focus of this chapter is pregnancy recognition signals in subprimate mammals, which prevent luteolysis and ensure maintenance of an intrauterine environment that supports events associated with establishment and maintenance of pregnancy.

Regulation of Endometrial Responsiveness to Estrogen and Progesterone by Pregnancy Recognition Signals During the Periimplantation Period

Maternal recognition of pregnancy results from signaling between the trophoblast of the conceptus (embryo and associated membranes) and the maternal system (1). These signals ensure maintenance of structural and functional integrity of the corpus luteum (CL) that would otherwise regress at the end of the estrous or menstrual cycle. The CL produces progesterone that stimulates and maintains endometrial functions that support early embryonic development, implantation, placentation, and successful fetoplacental development. Primate and subprimate mammals possess different mechanisms for regulating estrous or menstrual cycle lengths and luteolysis. Prostaglandin F 2α (PGF) is responsible for the structural and functional demise of the CL in most, if not all, mammals. In primates uterine independent luteolysis is accomplished via intraovarian factors that include PGF, and establishment of pregnancy requires a luteotropic signal, chorionic gonadotropin (CG), from the conceptus (2). In subprimate mammals CL lifespan is controlled by PGF from the uterus, and pregnancy recognition signals are paracrine hormones that prevent endometrial production of luteolytic PGF. Antiluteolytic signals include interferon tau (IFNτ) in ruminants, estrogen and prolactin in pigs, and, perhaps, placental lactogens in species such as rodents.