Reproduction in Domestic Animals

Factors Affecting Oocyte Quality 397capture by infundibulum after ovulation and to fertilizationregulation (Van Soom et al. 2002).During the last few years, increasing lines of evidenceshave suggested that the oocyte itself also regulates manyparameters of follicular somatic cells proliferation anddifferentiation. The TGF-b superfamily gathers morethan 35 members involved in the regulation of severalphysiological processes in mammals. In particular,TGF-b, members are strongly involved in many aspectsof ovarian function regulation (Knight and Glister2006). This superfamily includes different families ofgrowth factors such as TGF-b family, bone morphogeneticproteins (BMP), growth and differentiation factors(GDF), activin ⁄ inhibin and anti-mullerian hormone. Italso includes type I and type II receptors acting throughSmad signalling to modulate target genes expression, aswell as non-signalling secreted or membrane-boundbinding proteins that may regulate TGF-b familymembers’ biologic activity. TGF-b family membersoriginated from somatic follicular cells are involved inthe regulation of several aspects of follicular growthinitiation and progression (Knight and Glister 2006). Inaddition, GDF-9, BMP-15 (also called GDF-9B) andBMP-6 have been shown to be produced by oocytesfrom the primordial follicle stage (McNatty et al. 2001).In mouse, GDF-9 knockout induces arrest of folliculardevelopment at the primary stage and sterility (Donget al. 1996) and GDF-9 may also be involved inprimordial to primary follicle transition in the rat ovary(Vitt et al. 2000). Oocyte secreted factors are necessaryto induce the differentiation of pre-antral mouse granulosacells to cumulus cells [ability to expand uponepidermal growth factor (EGF) stimulation (Diaz et al.2007)]. In the sheep, naturally occurring inactivatingmutations of GDF-9 or BMP-15 increase ovulation ratein heterozygous ewes while homozygous females areinfertile and active immunization against GDF-9 andBMP-15 blocks folliculogenesis at the primary stage inewe (McNatty et al. 2005). During antral folliculargrowth, GDF-9, BMP-15 and BMP-6 promote granulosacells proliferation and modulate their sensitivity toFSH, thus participating to the selection of the dominantfollicle (Knight and Glister 2006). In addition, it hasbeen shown recently in bovine that oocyte-secretedBMP-6 and BMP-15 are protecting cumulus cellsagainst apoptosis occurring during culture of cattleCOC (Hussein et al. 2005) and GDF-9 preventspremature differentiation (luteinization) of bovine granulosacells (Spicer et al. 2006). Recently, JY-1 has beendiscovered as another oocyte-specific secreted factormodulating granulosa cell functions (Bettegowda et al.2007), highlighting again the central role of oocyte andOSF in the regulation of follicular growth.In addition, the oocyte is able to regulate surroundingsomatic cells function through the modulation of theirmetabolism. Subtractive suppressive hybridizationallowed to identify six genes involved in glycolysis thatwere overexpressed in mouse cumulus cells as comparedwith mural granulosa cells of antral follicles and thisoverexpression was dependant on the presence of theoocyte or of OSF (Sugiura et al. 2005). More recently, ithas been established that this oocyte regulation ofcumulus cells glycolysis is mediated by GDF-9 andFGF-8 OSF cooperation (Sugiura et al. 2007). In thesame way, GDF-9 and BMP-15 promote cholesterolsynthesis by cumulus cells (Su et al. 2008). This cholesterolmay be useful to oocyte that is unable to produceit. Interesting oocyte grafting experiments in mice(Eppig et al. 2002) showed that, placed in similarenvironment, oocytes collected from secondary follicleswere more able to promote follicular growth with appropriatemural granulosa ⁄ cumulus cell differentiation (LHFig. 3. Two hypotheses to explain the increasing ratio of competent oocytes in growing follicular populations. (a) Primordial follicles entergrowth phase, oocytes are not yet competent (open circles). By the time of antrum formation, all oocytes become meiotically competent (grey),few are already developmentally competent (black). During further growth, some follicles are lost in atresia, whatever the status of their oocyte.During further follicular growth, the proportion of competent oocytes increases because of ongoing oocyte differentiation. More follicles are lostduring terminal growth. (b) Early follicular growth is similar. Because their oocytes are less able to drive follicular growth, follicles enclosing lessdevelopmentally competent oocytes (grey) are lost in atresia, whereas follicles containing developmentally competent oocytes (black) continuetheir growth. Finally, only follicles containing fully competent oocytes reach ovulationÓ 2008 The Authors. Journal compilation Ó 2008 Blackwell Verlag