1 Progesterone as the Driving Regulatory Force Behind Serum FSH Concentrations and Antral Follicular Growth in Cyclic Ewes

Abstract

Ovarian antral follicles in sheep grow in an orderly succession, producing typically 3 to 4 follicular waves per 17-day estrous cycle. Each wave is preceded by a transient increase in circulating FSH concentrations. The mechanism controlling the number of recurrent FSH peaks and emerging follicular waves remains unknown. During the ewe's estrous cycle, the time between the first 2 FSH peaks and days of wave emergence is longer than the intervals separating the ensuing FSH peaks and follicular waves. The prolonged inter-peak/inter-wave interval occurs early in the luteal phase when low levels of progesterone are secreted by developing, or non-fully functional, corpora lutea. The purpose of the present study was to determine the effect of varying progesterone (P4) levels on circulating concentrations of FSH and antral follicular development in sheep. Exogenous P4 (15 mg per ewe i.m.) was administered twice daily to 6 cycling Rideau Arcott × Dorset ewes from Day 0 (ovulation) to Day 4 (the mean duration of the inter-wave interval); 6 animals served as controls. Follicular growth was monitored in all animals by daily transrectal ultrasonography (Days 0 to 9). Jugular blood samples were drawn twice a day from Day 0 to 4 and then daily until Day 9 to measure systemic concentrations of P4 and FSH. The first FSH peak post-ovulation was detected on Day 1.4 ± 0.2 and 4.0 ± 0.2 in treated and control ewes, respectively (P < 0.05). The next FSH peak(s) occurred on Days 3.4 ± 0.3 and 5.2 ± 0.2 in the treatment group and on Day 5.5 ± 0.3 in controls. Consequently, the treatment group had, on average, 3 follicular waves emerging on Days 0, 3, and 6, whereas the controls produced 2 waves emerging on Days 0 and 5 (P < 0.05).We then retrospectively analyzed and compared daily serum concentrations of P4 and FSH obtained in cyclic Western White Face ewes (Columbia × Rambouillet) that had 3 (n = 10) or 4 (n = 19) follicular waves per cycle. Mean P4 concentrations were greater (P < 0.05) in sheep with 4 waves per cycle compared with their counterparts, which had 3 waves of follicular growth. Interestingly, the ewes with 3 waves exceeded (P < 0.05) all animals with 4 follicular waves in mean serum FSH concentrations on Days 0 to 2, 6 to 7, and 9 to 15 post-ovulation. In summary, creation of mid-luteal phase levels of P4 in metestrus shortened the time to the first post-ovulatory FSH peak in ewes, resulting in emergence of one more follicular wave compared with control animals during the same time frame. The ewes exhibiting 4 waves of follicular emergence had greater serum levels of P4 but lower FSH concentrations compared with sheep with 3 waves per cycle. Therefore, progesterone appears to be a key endocrine signal governing the control of periodic increases in serum FSH concentrations and the number of follicular waves in cyclic sheep. This study was funded by OMAFRA and NSERC grants. Appreciation is extended to Norman C. Rawlings, Susan Cook, and Sekallu Srinivas (University of Saskatchewan) and the staff at Ponsonby Sheep Research Station.

Intrinsic determinants and predictors of superovulatory yields in sheep: Circulating concentrations of reproductive hormones, ovarian status, and antral follicular blood flow

“…7). This is most likely due to alterations in intermediate FSH metabolism induced by a rapid change in steroid milieu [75,76]. Lower serum levels of P 4 or synthetic progestin tend to increase the less acidic isoforms of FSH in circulation causing FSH to be cleared from the blood at a faster rate [77].…”

A meta‐analysis of mRNA expression profiling studies in sheep with different FecB genotypes

“…Many members of the TGFβ family are considered important intraovarian growth factors (Shimasaki et al, 2004). The FecB mutation affects the inhibitory function of the BMP4/GDF5 ligands by inhibiting the activity of BMPR-IB and increasing progesterone levels (Ruoss et al, 2009), which appears to be a key endocrine signal that controls the cyclical increase in ovine serum FSH concentration and the number of follicular waves (Baby & Bartlewski, 2011). Early research has shown that interference with BMPRIB expression inhibits estradiol production while inducing apoptosis in granulosa cells F I G U R E 9 Changes in mRNA and protein expression in the different genotypes (FecB).…”