Reproduction in Domestic Animals

Follicles and Mares 227Studies involving intrafollicular factor injection in mareshave provided insight into the complex interrelationshipsbetween these factors during follicle deviation(Ginther et al. 2005). It has been concluded thatalthough all these factors are likely involved in thedevelopment of the dominant follicle after the beginningof deviation, only IGF-1 is involved in the initiation ofdeviation by, among other actions, regulating the levelsof other growth factors in the dominant follicle (Beg andGinther 2006). This is consistent with the particularlyimportant role of the IGF-1 system in follicle selectionin other species (Mazerbourg et al. 2003). Results froma series of in vivo experiments have convincinglyconfirmed the critical role of the IGF system in follicleselection in mares. Injection of IGF-1 into the secondlargest or a smaller follicle at the beginning of deviationchanged its fate from subordinate to co-dominantresulting in the development of multiple ovulatoryfollicles (Ginther et al. 2004a; b; Gastal et al. 2007).Conversely, injection of IGF binding protein (IGFBP)-3into the largest follicle at the beginning of deviationresulted in the follicle regressing and being replaced bythe second largest follicle which became dominant(Ginther et al. 2004a). At least four types of IGFBPs(IGFBP-2, 3, 4 and 5), which negatively regulate IGFactivity, have been identified in equine follicles and theconcentrations of three of these (IGFBP-2, 4 and 5) arecorrelated negatively with those of IGF-1 during follicledevelopment (Gerard and Monget 1998; Bridges et al.2002). Consistent with the stimulatory role of IGF-1 inthe development of ovulatory follicles, reduced levels ofbioactive IGF-1 are thought to be involved in thedevelopmental deficiencies of dominant follicles duringthe spring transition that prevent them from acquiringovulatory competence (Acosta et al. 2004; Watson et al.2004).An additional factor that has begun to be explored inrelation to follicle selection in horses is VEGF. Thisangiogenic factor has been shown to be necessary forfollicle development in other species (Fraser and Wulff2001). VEGF levels differentially increase in the dominantfollicle in horses (Ginther et al. 2004b), and thisincrease is thought to be mediated, at least partly, byIGF-1. VEGF is likely involved in the reported increasein vascularization of the future dominant follicle beforethe beginning of deviation (Acosta et al. 2004) whichpresumably increases the availability of circulatinggonadotropins to the follicle. The reduced levels offollicular VEGF and low vascularity of the wall ofdominant follicles during the spring transition relative tothe ovulatory season (Watson and Al-zi’abi 2002)underscore the critical role of VEGF in the developmentof the ovulatory follicle in horses.Effects of Different Physiological Conditions onFollicle Development in MaresEffects of season. The effects of season on follicularactivity in mares have been studied in considerabledetail. Important variations in follicular activity occurnot only between the ovulatory and anovulatory seasonsbut also between different periods within each season.Studies in pony mares using follicle ablation to facilitatethe identification of individual follicular waves revealedthat, as during the ovulatory season, follicular wavesperiodically occur during the anovulatory season despitethe reduced levels of follicle development (Donadeu andGinther 2002b, 2003; Ginther et al. 2003b). Only minorwaves (largest follicle 12 mm within waves (means of 3.2 and 11.5follicles in waves developing during deep anoestrous andthe early spring transition, respectively). Althoughdominant follicles during transition may not grow tothe diameters typical of ovulatory follicles, in the samestudy transitional waves produced more follicles thanwaves developing during the ovulatory season (means of11.5 and 6.0 follicles >12 mm, respectively) attesting tothe high levels of follicular activity even in the absenceof ovulation in transitional mares (Donadeu and Ginther2003).Based on consistent temporal relationships betweenfollicles and circulating hormones, it has been concludedthat the differences in follicle development betweendifferent periods of the anovulatory season as well as thedeficient development of dominant follicles during thespring transition relative to the ovulatoy season are notattributable to deficient circulating FSH levels butrather to changes in LH and, possibly, differences infollicular sensitivity to gonadotropins (reviewed inDonadeu and Watson 2007).Season-related effects on follicular activity have alsobeen reported between the two halves of the ovulatoryseason, with higher levels of activity during the first halfof the season due to higher incidence of both secondarywaves and minor waves associated with higher gonadotropinlevels (Ginther 1992, 1993).Effects of pregnancy and parturition. Considerableresearch work is needed to better characterize folliculardynamics and associated regulatory mechanisms duringand following pregnancy in the mare. Based on combineddata from ultrasound and rectal palpation studies,follicular dynamics during the first half of pregnancyare similar to those occurring during the first half ofthe anovulatory season, with an initial period of variableactivity (between days 11 and 40 of pregnancy) characterizedby the periodic development of major waves or,more commonly, development of sporadic major wavesor only minor waves (Ginther and Bergfelt 1992),followed by a pronounced decrease in follicular activityin all mares between days 50 and 140 of pregnancy sothat the diameter of the largest follicle does not exceed15 mm by day 140 (Squires et al. 1974). A decrease infollicular activity has also been reported after the firstone-third of pregnancy in cattle (Ginther et al. 1996).Ó 2008 The Authors. Journal compilation Ó 2008 Blackwell Verlag