Ovarian function in ewes made hypogonadal with GnRH antagonist and stimulated with FSH in the presence or absence of low amplitude LH pulses

Abstract

This study examined the effect of LH pulses, of similar amplitude and frequency to those found in the luteal phase, on the pattern of hormone secretion and follicle development in GnRH antagonist-suppressed ewes stimulated with exogenous FSH. This experiment was conducted on ewes with ovarian autotransplants in a continuous study. Follicle development was suppressed in 18 ewes by 3 weeks of GnRH antagonist treatment (50 µg/kg per 4 days s.c.), and was then stimulated by infusion of ovine (o)FSH (5 µg NIADDK-oFSH-16/h i.v.) for 3 days. In addition to FSH, 10 animals received pulses of LH (2·5 µg NIADDKoLH-26 i.v.) every 4 h for the entire period of the FSH infusion. The follicle population was determined by daily ultrasound. Samples of ovarian and jugular venous blood were collected at 4-h intervals over the period of the FSH infusion and there were three periods of intensive blood sampling (15-min intervals for 2·5 h at 24, 48 and 72 h after the start of the FSH infusion) when the steroidogenic capacity of the follicles in all 18 ewes was tested around an LH challenge (2·5 µg i.v.).GnRH antagonist treatment resulted in a 57% decrease in FSH concentrations and prevented ovarian follicle development beyond 3 mm in diameter. Infusion of FSH resulted in a 60% increase in FSH concentrations and stimulated the development of large antral follicles and a coincident increase in ovarian androstenedione, inhibin and oestradiol secretion in both experimental groups. In the absence of 4-hourly LH pulses basal steroid secretion was negligible (<1 ng/min; P<0·001). Daily LH challenges, however, revealed no difference in the steroidogenic capacity of the follicle population in either experimental group. Similarly, LH pulses had no effect on the growth rate and number of antral follicles stimulated by FSH infusion, or the pattern of ovarian inhibin secretion.In conclusion, these results show that while FSH alone can stimulate the development of ovulatory sized follicles in ewes made hypogonadal with GnRH antagonist, physiological patterns of LH stimulation have no deleterious effects on FSH-stimulated follicle development and are essential for normal steroidogenesis.

Effect of recombinant follicle stimulating hormone (rFSH) on some fertility parameters in Awassi ewes synchronized with PGF2α in the breeding season

“…The follicular response induced by a single injection of the chimeric protein also reflects the long-lived nature of the single-chain gonadotropin analogs in sheep (9). Lemke et al (27) demonstrated that the single-chain analogs of the human gonadotropins were also active in sheep.…”

Single-chain human gonadotropin analogs induce follicle development in sheep

“…As in other species (Richards 1980), E 2 synthesis in sheep requires input from both the thecal and granulosa cells (Baird 1977, 1983, England et al 1981. The essential role of the gonadotropins in ovarian function is illustrated by the arrest offollicle development and E 2 synthesis in mature ewes made deficient in the gonadotropins by hypophysectomy (Draincourt et al 1987), hypothalamopituitary disconnection (Hudson et al 1999), immunoneutralization of endogenous GnRH (McNeilly et al 1986), or administration of long-lived GnRH agonists (McNeilly & Fraser 1987) or antagonists (Campbell et al 1998). Moreover, follicle development and E 2 synthesis are reinstated in gonadotropin-deficient sheep by administration of LH and FSH (Campbell et al 1998).…”

“…In sheep, ovarian weight is dramatically reduced, and follicle maturation and ovulation are blocked after the removal of gonadotropin support by hypothalamo-pituitary disconnection (Hudson et al 1999), hypophysectomy (Dufour et al 1979), immunoneutralization of gonadotrophin-releasing hormone (GnRH; Sakurai et al 1992), or administration of GnRH antagonists (Campbell et al 1998). These anti-gonadal responses are reversed by administration of supplemental gonadotropic stimuli (Fry et al 1988, Campbell et al 1998. The magnitude of the ovarian response increases with progressive increase in the level of exogenous gonadotropin administration and high levels of supplemental FSH induce a superovulatory response (McGowan et al 1985, Hudson et al 1999.…”

Gonadotropin requirements for dominant follicle selection in GnRH agonist-treated cows

“…10 mm in diameter in the absence or presence of LH. The ability of FSH alone to promote follicular growth to preovulatory sizes has been demonstrated in sheep that were treated with a GnRH antagonist and exogenous FSH for at least 3 days (Campbell et al 1998. However, in studies conducted with GnRHa (Gong et al 1996, Garverick et al 2002 or GnRH-immunized heifers (Crowe et al 2001), treatment with exogenous FSH for 48 h did not result in follicle growth greater than 9 mm in diameter.…”