Reproduction in Domestic Animals

Dominant Follicle Selection in Cows, Mares and Women 51early plateau before DF selection (inhibin-A) or a peakon the day of DF selection (oestradiol) while FSHconcentrations decline (Bleach et al. 2001; Kaneko et al.2002; Parker et al. 2003). Follicular inhibin-A secretionappears to be the most important regulator of FSHconcentrations during initial follicle wave growth incattle and is aided by oestradiol secreted from the DF atthe onset of dominance (Ginther et al. 2000, 2001a;Mihm and Bleach 2003): when atresia of growing cohortfollicles is caused using exogenous steroid treatmentsinhibin-A declines rapidly followed by a rise in FSHconcentrations despite high systemic oestradiol (Mihmet al. 2001). Similarly, FSH only rises again during lossof dominance of the first DF of the cycle when inhibin-Aconcentrations reach their nadir, despite oestradiolhaving declined two days previously (Bleach et al.2001). However, other follicular secretions may also beinvolved in the regulation of FSH during cohort growthsuch as follistatin (Mihm and Bleach 2003).In mares oestradiol concentrations rise in circulationapproximately 1 day before selection of the DF andluteolysis (Bergfelt et al. 2001). As FSH concentrationsdecline immediately after wave emergence which isseveral days from deviation, other follicular secretionsthan oestradiol must be responsible for the initial FSHsuppression. Inhibin-A is synthesized by cohort andDFs in the mares (Watson et al. 2002) and rises in totalinhibin have been observed associated with DF growth(Bergfelt et al. 2001). In women, similar to cows,oestradiol concentrations show a small but significantincrease after wave emergence. Very importantly, however,inhibin-B concentrations rise during cohort growthand appear to peak just before DF selection, decliningduring the long dominance period (Muttukrishna et al.2000). Thus, inhibin-B secretion from cohort folliclescontrols the initial FSH decline responsible for DFselection in women (Schneyer et al. 2000). Followingselection of the ovulatory DF in the follicular phase,oestradiol and inhibin-A concentrations rise rapidly,and together control the remaining protracted FSHdecline (Muttukrishna et al. 1994, 2000). In contrast tocattle, where oestradiol only exerts a transient inhibitionon FSH (O’Rourke et al. 2000), oestradiol is clearlyrequired for continued FSH suppression in women, asanti-oestradiol treatment (passive immunization orreceptor antagonist administration) during the midfollicularand the end-follicular phase will cause a rise inFSH and abolish DF selection or cause DF atresia(Zeleznik 2001).Intraovarian (Cellular) Mechanisms for DFSelection: Gonadotrophin Responsiveness andInsulin-like Growth Factor Binding Protein(IGFBP) ExpressionAntral follicles of 2–5 mm (cows, women) or 10–13 mm(mares) are clearly dependent on elevated FSH forcontinued development, firstly because they undergoatresia in the absence of FSH rises, and secondly, cohortfollicles undergo atresia after their emergence when FSHdeclines again following its transient rise. At deviationbovine DFs can maintain follicular cell proliferation andenhance oestradiol production despite declining FSHconcentrations, and the DF may be the one cohortfollicle with the lowest FSH requirement due toincreased or maintained high FSH receptor mRNAexpression and FSH-binding allowing it to pass the8.5 mm diameter threshold (Ireland and Roche 1983;Evans and Fortune 1997; Bao and Garverick 1998;Rozell et al. 2005). Interestingly, the follicle with highestintrafollicular oestradiol 33 h after the FSH peak (themost successful cohort follicle in the wave) also hashighest activin-A concentrations in follicular fluid(Austin et al. 2001), which is known to increase FSHreceptor expression in granulosa cells (Knight andGlister 2006). This information is extended to women,where it is postulated that the follicle which becomes theDF must first develop ‘activin-dominance’ before the‘inhibin-dominance’ characteristic for the DF (Schneyeret al. 2000).In all three monovulatory species a transition fromFSH- to LH-dependence is postulated as the mechanismwhich allows continued development of theselected DF (Ginther et al. 2001a), and in the animalspecies this is based on functional studies abolishing oradding LH pulses during follicle wave growth and afterDF selection (Gastal et al. 1999; Mihm and Bleach2003). Granulosa cells from newly selected bovine DFhave acquired an enhanced ability to bind LHcompared with SF1s and show increased mRNAexpression for the LH receptor during their earlygrowth phase (Ireland and Roche 1983; Evans andFortune 1997; Bao and Garverick 1998; Evans et al.2004; Mihm et al. 2006). Similarly, in mares theselected DF is characterized by its absolute dependenceon increased LH for enhanced oestradiol synthesis andcontinued growth (Bergfelt et al. 2001). This alsoapplies in women, as it is suggested that LH-inducedcAMP production in granulosa cells from DF replacesthe FSH-stimulated cAMP production seen in growingcohort follicles (Zeleznik 2001). However, at this pointit is not clear in any species whether the identifiedincrease in LH receptor expression in the DF is cause(will the first follicle that acquires LH receptor activitybecome selected?) or consequence of the selectionprocess. Recently a slight increase in LH receptormRNA expression was detected in granulosa cells fromthe largest bovine follicle a few hours before the onsetof deviation and the appearance of morphological andhormonal (follicular fluid oestradiol) differences, comparedwith the second largest follicle (Beg et al. 2001).This may indicate that acquisition of increased LHreceptor expression characterizes the follicle with thedevelopmental advantage even before other differencesto the cohort become apparent. As IGF1 has beenshown to enhance FSH-induced granulosa cell differentiation,particularly LH receptor acquisition (Hirakawaet al. 1999), the increased free IGF concentrationspostulated for the future DF during cohort growth (seebelow) may be responsible for such a developmentaladvantage.Because FSH is anti-apoptotic, proliferative anddifferentiative (it stimulates aromatase production andLH receptor acquisition), enhanced FSH-responsivenessor the ability to amplify FSH-stimulated granulosacell functions in one cohort follicle may lead toÓ 2008 The Authors. Journal compilation Ó 2008 Blackwell Verlag