Reproduction in Domestic Animals

Embryo Biotechnologies in Farm Animals 52003a). This second method has been developed followingthe finding that mouse ES cells grown in a serumsupplementedmedium and LIF can be differentiatedinto neuroectodermal cells by serum and LIF withdrawal(Ying et al. 2003b). The role of BMP moleculesis to counteract and block the induction of neuraldifferentiation and fix the undifferentiated state in aclever balance between conflicting inductive signallingpathways. Other recent protocols, based on the stimulationof the nodal-activin signalling pathways, havebeen shown to maintain the undifferentiated proliferationof human and mouse ES cells (James et al. 2005;Vallier et al. 2005; Brons et al. 2007; Ogawa et al. 2007).A particular attention should be paid to very recentreports of a novel stem cell type derived from mouseembryos and called epi stem cells (EpiSCs) (Brons et al.2007; Tesar et al. 2007). Interestingly, mouse EpiSCshave been shown to be very similar to human ES cells inmorphology, growth factor requirement and geneexpression (Brons et al. 2007; Tesar et al. 2007) whilemouse ES cells differ considerably from human ES inculture requirements for the maintenance of the undifferentiatedstate, growth rate and response to inductivesignals. Another important difference between mouseES cells and EpiSCs is the fact that only the formerare capable of giving rise to chimeric offspring followingblastocyst injection. Under the present status ofresearch, epiSC derivation in farm animals may proveeasier than true ES cell derivation and could representa significant step forward towards the understandingof the requirements for maintaining pluripotencyin cultured inner cells mass cells of farm animalembryos.From an applied perspective, embryonic stem cells infarm animals are important for several reasons but themost relevant is to provide a method to introduceprecise genetic modification into animals by homologousrecombination of ES cells (Lombardo et al. 2007)followed by blastocyst injection for chimera derivationand breeding, or by somatic cell nuclear transfer. Asecond important objective is to provide large animalmodels in which the ES cell technology can be tested fortissue-specific differentiation (Brown et al. 2007) and celltherapy of various tissues and organs. Conventional EScells, carrying all the properties of mouse ES cells, canserve both purposes but epiSCs can serve at least thesecond. Therefore, ES and epiSC research still deservesmajor research efforts and represents the frontier ofreproductive technologies in farm animals both foragriculture and biotechnological applications.ConclusionsThe manipulation of early embryonic development infarm animals is of foremost importance both foragriculture and biotechnology applications but also asa model to study some basic aspects of reproduction anddevelopmental biology. In the agricultural context,reproductive biotechnologies in farm animals areexpected to play an increasing role in the next decadesdue to the growing demand for agricultural productsfrom the emerging economies worldwide (see ‘TheEconomist’, The end of cheap food, 7–14 December2007). Modern reproductive biotechnologies, togetherwith the most recent molecular techniques of genomics,proteomics and transgenesis are the powerful tools thatwill provide the answers to the rapidly changing worldscenario of food demand. In the biomedical field, largeanimals represent increasingly important research modelsespecially in the stem cell field, for creating diseasemodels and genetically modified animals as potentialdonors of tissues and organs for xenotransplantation.These are the reasons why large animal research, thatshort-sighted worldwide research policies have neglectedin recent years, will regain a leading role in the comingfuture.Finally, successful translation of large animal researchinto commercial enterprise requires solid science, longtermresource commitment, and extensive steps ofvalidation to reach the thresholds of reproducibilityand profitability. Therefore, strong scientific drive,vision and entrepreneurial skills are all needed forcontributing to progress in large animal reproductivesciences.AcknowledgementsA successful career in animal reproduction is the result of a full-timetotal dedication to the work but also of good training, a stimulatingenvironment and interaction with peers around the world. For thisreason, we want to acknowledge the many colleagues and collaboratorswhose support over the years has been instrumental to success inour work. In particular, we want to acknowledge Professor A Lauria,who during our years as undergraduate students transmitted to us hisenthusiasm for animal reproduction, and especially Dr. Robert Moor,our mentor for many years, who gave us vision and inspired most ofthe work that we have been doing in the last 20 years and we willprobably be doing for the next 20 years.ReferencesBrackett BG, Bousquet D, Boice ML, Donawick WJ, EvansJF, Dressel MA, 1982: Normal development followingin vitro fertilization in the cow. Biol Reprod 27, 147–158.Brons IG, Smithers LE, Trotter MW, Rugg-Gunn P, Sun B,Chuva de Sousa Lopes SM, Howlett SK, Clarkson A,Ahrlund-Richter L, Pedersen RA, Vallier L, 2007: Derivationof pluripotent epiblast stem cells from mammalianembryos. Nature 448, 191–195.Brophy B, Smolenski G, Wheeler T, Wells D, L’Huillier P,Laible G, 2003: Cloned transgenic cattle produce milk withhigher levels of beta-casein and kappa-casein. 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