Decline in Serum Follicle-Stimulating Hormone Concentrations Alters Key Intrafollicular Growth Factors Involved in Selection of the Dominant Follicle in Heifers1

Abstract

Declining FSH after a transient rise coincides with selection of a dominant follicle (DF) and atresia of the remaining cohort follicles (subordinates) in cattle. The objectives of this study were to determine 1) whether intrafollicular amounts of inhibins, activin-A, insulin-like growth factor I (IGF-I), and IGF-I-binding proteins (IGFBP) are altered during selection of the first-wave dominant follicle (DF1) and 2) whether these biochemical markers are FSH dependent. Beef heifers received six or eight 6-h injections of saline (controls) or eight 6-h injections of recombinant bovine FSH (1 mg/injection) at 38 to 42 h after estrus (Day 0). Daily ultrasound scanning was used to define selection of DF1. Controls (n = 6 per group) were ovariectomized 1) on Day 3 of the estrous cycle before DF1 selection (preselection follicles) and 2) after DF1 selection on Day 4.8 +/- 0.5. In controls, FSH declined between Days 2 and 3 and selection of DF1 occurred between Days 3 and 5. During this interval, intrafollicular estradiol concentrations increased > 5-fold in DF1, yet declined 4-fold in subordinates (p < 0.05). In DF1, total IGF-I increased 1.3-fold (p < 0.05), whereas the amounts of the 40- to 47-kDa and the 35-kDa IGFBP (ligand hybridization) decreased 2.4- and 2.5-fold, respectively (p < 0.05), compared to values in preselection follicles on Day 3; total dimeric inhibin-A decreased 1.8-fold (p < 0.05). In contrast, amounts of the 30- to 32-kDa IGFBP increased 12.4-fold (p < 0.05) in subordinates on Day 4.8 compared with preselection follicles on Day 3, while the amount of inhibins > 34 kDa decreased 4- to 9-fold (p < 0.05). In FSH-treated heifers, both selection of DF1 and atresia of subordinates were delayed by 2.2 days. Preselection follicles recovered on Day 4.9 +/- 0.1 from FSH-treated heifers were similar (p > 0.05) in almost all biochemical parameters to preselection follicles from control heifers; however, they differed markedly from both DF1 and subordinate follicles recovered from control heifers on Day 4.8 +/- 0.5. In conclusion, the decline in FSH beginning after Day 2 of the heifer estrous cycle causes differential alterations in FSH-dependent growth factors and hormones within the cohort of preselection follicles, simultaneously inducing growth and enhanced estradiol-producing capacity of the DF and atresia of subordinate follicles.

Differentiation of the bovine dominant follicle from the cohort upregulates mRNA expression for new tissue development genes

“…This conclusion is based on the previously described timing of growth of the first follicle wave of the oestrous cycle, intrafollicular hormone concentrations and the fact that, while morphologically unselected and still FSH 'dependent', the most oestrogenic cohort follicle 1-2 days after wave emergence will most likely become the DF (Mihm et al 1997, Austin et al 2001. Growth characteristics and differences in diameter, steroid concentrations and oestrogenic activity established in this study showed the higher differentiation state of the DF recovered at or shortly after the onset of dominance in accordance with previous characterisations of selected DFs (Ginther et al 2003, Mihm & Bleach 2003.…”

“…These two transcripts encoded a novel 3 0 truncated aromatase variant (deposited under NCBI accession number DQ004742 and recently matched to Bt.4447), and an untranslated mRNA sequence recently matched to the UniGene cluster Bt.33875 (deposited under NCBI accession number AY999166). In addition, SAGE analysis of transcripts upregulated in the DF granulosa cells confirmed four known genes encoding cytochrome P450 aromatase (CYP19A1), glutathione S-transferase A2 (GSTA2), inhibin a-subunit (INHA) and glia-derived nexin (SERPINE2), which regulate follicular E synthesis, antioxidant activity and extracellular tissue remodelling in the selected DF (Mihm et al 1997, Sisco et al 2003, Evans et al 2004, Fayad et al 2004.…”

“…Thus, the DF and SF were recovered at the onset of dominance in the DF (three cows) or 12 h after (one cow) based on morphological and hormonal criteria ( Fig. 1; Table 1; Mihm et al 1997, Austin et al 2001.…”

Follicle selection in cattle and horses: role of intrafollicular factors

“…Results of many studies are compatible with a role for the IGF system in deviation but seem at least partly equivocal, owing to one or more of the following: (1) the reference point was not readily related to the beginning of deviation (Mihm et al 1997, Spicer et al 2005; (2) a differential change between LF and second LF began at the equivalent of the beginning of deviation, rather than before the beginning of deviation (Beg et al 2001, Ginther et al 2003b or (3) total IGF-I rather than free IGF-I was considered (De la Sota et al 1996, Mihm et al 1997. In cattle, the concentrations of free IGF-I did not increase in the LF in association with deviation, but began to decrease in the second LF before the beginning of deviation (Figs 2 and 3, Beg et al 2002).…”

Follicular dynamic and ovulation in cattle – a review

“…In conclusion, the decline in FSH beginning after Day 2 of the heifer oestrous cycle causes differential alterations in FSH dependent growth factors and hormones within the cohort of preselection follicles, simultaneously inducing growth and enhanced estradiol producing capacity of the DF and atresia of subordinate follicles (MIHM et al, 1997).…”