Follicular dynamics and endocrine changes in prepubertal calves

Groups of Holstein calves were slaughtered at monthly intervals to study ovarian growth. Ovarian weight increased up to 4 months of age, plateaued from 5 to 8 months of age and then increased further as heifers began to cycle and develop corpora lutea (8-12 months of age). The number of antral follicles reached a peak at 4 months of age, declined from 4 to 8 months and remained relatively constant thereafter (DESJARDINS and HAFS 1969). In a recent study RAWLINGS et al.

(2003), measured ovarian length and width as well as the diameter of the vagina, the cervix and the uterine body weekly by transrectal ultrasonography beginning with 2 week old calves and continuing until they had reached 60 weeks of age. Ovarian dimensions (length and width) increased from 2 to 14 weeks of age and again from 34 to 60 weeks of age. The first antral follicles were present at 2 weeks of age. The number of follicles ≥3 mm in diameter and the maximum follicle diameter increased in a similar biphasic pattern to that of ovarian morphology. Diameters of the uterus, the cervix and the vagina initially increased rapidly until 20-24 weeks of age, and then increased again after 32 weeks of age. These recent data and together with observations by DESJARDINS and HAFS (1969) confirm that in prepubertal calves, the development of ovarian antral follicles and tubular genitalia occur in parallel.

Daily ultrasonographic observations over extended periods of time have shown that prepubertal calves have antral follicular waves, similar to those observed in adult cows (PIERSON and GINTHER 1988; SAVIO et al. 1988; ADAMS et al. 1994). Each follicular wave was also preceded by a peak of FSH and the periodicity and follicle size ranges were similar to that in adult cows (EVANS et al. 1994b). In beef heifers examined over periods of a least 17 days from 2 weeks of age until first ovulation, it was found that calves as young as 2 weeks of age already exhibited regular ovarian follicular waves (EVANS et al. 1994a). The number of small (3-5 mm in diameter), medium (6-8 mm) and large follicles (≥ 9 mm in diameter) increased from 2 to 14 weeks of age. Follicle diameter increased further from 24 to 44 weeks reaching a maximum of 13-14 mm in diameter at 44-56 weeks. First ovulation was observed at a range of 52 to 56 weeks of age (for review see RAWLINGS et al. 2003).

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Important endocrine changes are observed during the prepubertal period. LH and FSH secretion increases marked but transiently between 6 and 14 weeks of age, remains relatively constant from 14 to 32 weeks of age and LH secretion increases again until the first ovulation [Fig. 5] (SCHAMS et al. 1981; EVANS et al 1992;

EVANS et al. 1994a; EVANS et al. 1994b). LH secretion is pulsatile and the early increase in secretion appears to be mainly due to an increase in LH pulse amplitude rather than LH pulse frequency [Fig. 5] (EVANS et al. 1992; HONARAMOOZ et al.

1999). Subsequently, serum concentrations of LH and FSH remain low; LH pulse frequency increases over the last 40–80 days prior to first ovulation (DAY et al. 1987;

EVANS et al. 1994a; MELVIN et al. 1999). FSH serum concentrations remain relatively stable in the period prior to ovulation (EVANS et al. 1994a), with probably only a transient increase (MELVIN et al. 1999). Therefore, the early postnatal increase in gonadotropin secretion would appear to trigger the increase in ovarian antral follicle numbers and sizes.

2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60

Fig: 5. Schematic representation of the changes in mean circulating LH and FSH concentrations from birth to first ovulation in heifers.

The boxes show the relative pulsatile secretory profiles of LH over a 24-h period shortly after birth (a) and a few weeks before first ovulation (b). Adapted from RAWLINGS et al. 2003.

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During the peripubertal period, increased LH pulse frequency results in growth of larger antral follicles and increased estradiol production, over a 30 to 90 days period prior to first ovulation (MELVIN et al. 1999; RAWLINGS et al. 2003). The estradiol concentration in serum, which is associated with the termination of the growing phase of the dominant follicles tended to increase with age (EVANS et al. 1994b).

Progesterone increased prior to first ovulation, but was associated with waves of follicular development (EVANS et al. 1994a). An age-dependent increase was also observed in serum IGF-I concentrations from 3 months of age reaching a plateau after 9 months of age (KERR et al. 1991). Significant changes in the mean concentration and amplitude of GH pulses have also been observed just before puberty in beef heifers (YELICH et al. 1996).

The onset of puberty and sexual maturation are processes that are initiated well before birth but continue through prepuberty (> 50 days before puberty); peripuberty (50 days before puberty); and completed early after puberty. Although in prepubertal calves the hypothalamic-pituitary–ovarian axis is already involved in the regulation of follicular growth, this endocrine activity appears to be suppressed by a negative feedback until the heifer is of sufficient body size and in a state of metabolic maturity capable of successful reproduction (DAY et al. 1987). The hypothalamus appears to be the primary site of physiological change when sexual maturity occurs. At this point, there is a decrease in the negative feedback caused by estradiol, which allows increased LH secretion via an increased LH pulse frequency and enhanced antral follicle development and estrogen secretion. The negative feedback caused by estradiol appears to be exerted indirectly since estradiol receptors are not present on GnRH neurons (SHIVERS et al. 1983). It has been shown that endogenous opioids can mediate the effects of estradiol on LH secretion (WOLFE et al. 1991) and there are indications that opioidergic inhibition of LH can play an important role during the prepubertal period. Treatment of calves with the opioid antagonist naloxone increased LH concentration at 36 to 48 weeks of age, suggesting that the suppressive effect of opioids can be exerted in the mid to late prepubertal period (HONARAMOOZ et al. 2000). Similarly, in ovariectomized calves treated with naloxone and oestradiol, an increase in LH secretion was observed during the period

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in which intact control calves were initiating estrous cycles (WOLFE et al. 1991). This suggests that opioids and estrogen act synergistically to regulate LH secretion during sexual maturation in the bovine female. The enhanced LH secretion increases the production of estrogen from antral follicles causing a preovulatory LH surge and the first ovulation (for review see KINDER et al. 1995; RAWLINGS et al. 2003). First ovulation is followed by an ovulatory cycle of short duration with a transient increase of progesterone and small corpora lutea (EVANS et al. 1994a).

Metabolic hormones such as growth hormone and IGF-I have effects on the progress of sexual maturation in heifers. Prepubertal calves immunized against growth hormone-releasing factor (GRF) had decreased serum concentration of GH, IGF-I, estradiol and a delayed onset of puberty (SCHOPPEE et al. 1996; SIMPSON et al.

1991). Similarly, heifers fed to gain weight at low rates had lower concentrations of LH, IGF-I, insulin, and glucose than those gaining weight at a higher rate, and concomitantly puberty was delayed (YELICH et al. 1996).