Concentrations of Progesterone, Follistatin, and Follicle-Stimulating Hormone in Peripheral Plasma Across the Estrous Cycle and Pregnancy in Merino Ewes That Are Homozygous or Noncarriers of the Booroola Gene1

Abstract

The circulating concentrations of progesterone, FSH, and follistatin across the estrous cycle and gestation were compared in Australian merino sheep that were homozygous for the Booroola gene, FecB, or were noncarriers. The Booroola phenotype is due to a point mutation in the bone morphogenetic protein receptor 1B. Progesterone concentrations began to rise earlier and were higher in the Booroola ewes than in the noncarriers on most days of the luteal phase but not during the follicular phase of the cycle. Follistatin concentrations remained unchanged across the estrous cycle in both groups of ewes, with no differences between genotypes. FSH concentrations were higher in Booroola ewes than in noncarrier ewes on most days of the estrous cycle, with a significantly higher and broader peak of FSH around the time of estrus. Progesterone concentrations were significantly higher in early and midgestation in Booroola ewes but were lower toward the end of gestation than those in noncarriers. FSH declined in both groups across gestation, with lower concentrations of FSH in Booroola ewes during midgestation. Follistatin remained unchanged across gestation in Booroola ewes and noncarrier ewes with a twin pregnancy but declined across gestation in noncarrier ewes with a singleton pregnancy. These results suggest that follistatin concentration is not regulated by the FecB gene during the estrous cycle and pregnancy but is influenced by the number of fetuses. However, the FecB gene appears to positively affect both progesterone and FSH during the estrous cycle and across pregnancy, which suggests that bone morphogenetic proteins play an important role in the regulation of both hormones.

Ovarian follicle development in Booroola sheep exhibiting impaired bone morphogenetic protein signalling pathway

“…These results support the notion that BMPs exert dual functions within the ovary, potentially increasing rate of PGC formation and follicle recruitment, while also inhibiting progesterone formation and follicular maturation required for ovulation. BMPs also clearly have a role in the pituitary regulating gonadotrophin release particularly FSH (McNatty et al 1989, Xia et al 2003, thus when BMP signalling is attenuated FSH concentrations rise. This in turn stimulates a precocious maturation of multiple smaller follicles, hence multiple ovulation.…”

“…The assay was performed using a similar procedure to that was described by Xia et al (2003). Briefly, the antiserum was Any follicle falling within the counting frame and not intersecting these two forbidden lines was counted, while others were not counted.…”

“…The proposed mechanisms relate to evidence that granulosa cells of Booroola ewes are less sensitive to the inhibitory action of BMPs on progesterone synthesis (Shimasaki et al 2004). This results in follicles that mature smaller in size, higher concentrations of FSH during the oestrous cycle and increased progesterone production during the luteal phase of the cycle (McNatty et al 1989, Xia et al 2003. This results in increased progesterone production in turn, promoting ovulation rate and litter size (Shimasaki et al 2004).…”

Flow cytometric analysis of FSHR, BMRR1B, LHR and apoptosis in granulosa cells and ovulation rate in merino sheep

“…The cellular mechanism responsible for this increase, however, has not been revealed (Mulsant et al 2001, Souza et al 2001, Wilson et al 2001, Campbell et al 2003, Crawford et al 2011. Evidence from our previous findings in BB sheep has shown that the attenuation of BMP signaling produces elevated FSH levels, and the initial number of primordial follicles are reduced; yet the rate of recruitment of primary follicles is substantially lower and results in a greater retention of the ovarian reserve in the mature ewe (Xia et al 2003, Ruoss et al 2009). Given that FSHRs are not expressed in primordial follicles, it is unlikely that FSH plays a role in this initial recruitment (Ruoss et al 2009).…”

The impact of passive immunisation against BMPRIB and BMP4 on follicle development and ovulation in mice

“…However, it has been reported that BMPs inhibit the gonadotrophin-induced progesterone production by maturing follicles (Xia et al 2003, Pierre et al 2004, McNatty et al 2007, in addition to its inhibitory action on final cell differentiation (Cejalvo et al 2007),…”