Biol Reprod Track the topics, authors and articles important to you
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

BOR - Papers in Press, published online ahead of print May 28, 2003.
Biol Reprod 2003, 10.1095/biolreprod.102.005512
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
69/3/1079    most recent
biolreprod.102.005512v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow My Folders
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Xia, Y.
Right arrow Articles by McFarlane, J.R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xia, Y.
Right arrow Articles by McFarlane, J.R.
Agricola
Right arrow Articles by Xia, Y.
Right arrow Articles by McFarlane, J.R.
BIOLOGY OF REPRODUCTION 69, 1079–1084 (2003)
DOI: 10.1095/biolreprod.102.005512
© 2003 by the Society for the Study of Reproduction, Inc.

Pregnancy

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

Y. Xia3, T. O'Shea3, R. Murison4, and J.R. McFarlane2,3

Department of Physiology, School of Biomedical, Biological & Molecular Sciences3 School of Mathematics, Statistics and Computer Science,4 University of New England, Armidale, New South Wales 2351, Australia


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
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.

follistatin, menstrual cycle, pregnancy, progesterone


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Booroola sheep possess a major gene, FecB, that influences their ovulation rate [1]. Homozygotes (BB), heterozygotes (B+), and noncarriers (++) of the FecB gene are segregated on the basis of ovulation rates of >=5, 3 or 4, and 1 or 2, respectively [2]. The gene effects are due to a point mutation in the bone morphogenetic protein (BMP) receptor type IB [3–5], although the exact mechanism by which this mutation induces the increased ovulation rate remains to be determined.

In sexually mature ewes, differences in the morphology of the antral follicles have been consistently observed, with follicles maturing and ovulating at significantly smaller diameters in ewes carrying the Booroola gene than in normal merino ewes [6, 7]. The action of the Booroola gene has been generally associated with higher concentrations of FSH during the estrous cycle [8–10].

No differences were observed between Booroola and ordinary Merino ewes in peripheral concentrations of estradiol and androstenedione on the days samples were taken (Days 2, 9, and 16) during the estrous cycle [11]. Booroola ewes have been reported to have up to 25% higher progesterone concentrations than ordinary Merino ewes during the midluteal phase of the estrous cycle, but this difference was not significant [12] because of the small sample size. In the follicular phase of the estrous cycle induced by prostaglandin F2{alpha}, there were no gene-specific differences in concentrations of progesterone [13–15]. No differences were found in ovarian secretion rates of immunoreactive inhibins around luteolysis or in daily plasma concentrations throughout the estrous cycle, as measured by the Monash RIA [14]. More recently, plasma inhibin A concentration was determined using a specific two-site ELISA during the follicular and early luteal phases in ewes with an ovarian autotransplant, but no differences were noted between genotypes [13]. FSH and LH concentrations in plasma were not different between genotypes after treatment of ovariectomized ewes with estradiol, progesterone, or bovine follicular fluid, indicating the sensitivity of the hypothalamic-pituitary axis to ovarian hormones are similar for Booroola and ordinary Merino ewes [15].

Follistatin, originally identified and isolated from both bovine and porcine follicular fluids on the basis of its inhibition of pituitary FSH [16, 17] secretion, is a monomeric glycosylated polypeptide chain that binds activin with high affinity and neutralizes most but not all of its biological actions [18–20]. Follistatin also neutralizes the biological activity of several BMPs [21].

In a previous study, Klein et al. [22] showed that the peripheral concentrations of plasma follistatin in sheep increased during the luteal phase above follicular phase concentrations, peaking 10 days after the LH surge. However, the assay was subsequently shown to be affected by the presence of activin [23], leaving some doubt as to the validity of the results. Follistatin mRNA has been detected in ovine granulosa cells of preantral, antral, and early atretic follicles at all stages of the estrous cycle and in the corpora lutea (CL) at the early and midluteal stages of the cycle. However, only low levels of follistatin mRNA were observed in the presumptive preovulatory follicle [24, 25]. The maternal serum concentrations of follistatin rise during gestation and decrease after delivery in humans [26–28], suggesting that follistatin plays an important role during pregnancy and perhaps parturition.

The aim of this study was to examine in detail the changes in peripheral concentrations of progesterone and FSH and the role of follistatin. We used an assay that is not affected by activins to identify gene-specific differences during the estrous cycle and pregnancy between Booroola and ordinary Merino ewes.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Animals and Sample Collection

The ewes used in this study were classified as BB and ++ based on ovulation rate. One group of BB ewes (n = 5) and one group of ++ ewes (n = 5) were grazed on open paddocks and run with castrated male Merinos (wethers) that had received injections of 50 mg of a mixture of testosterone esters (Durateston; Intervet, Lane Cove, NSW, Australia) over the previous 2 mo. The wethers were harnessed with marking crayons so that the day of estrus (Day 0) could be determined in the ewes. Blood samples were taken daily from Day 0 by jugular venipuncture until the ewes were marked again, indicating the next estrus. Another set of BB ewes (n = 5) and ++ ewes (n = 10) were run with intact rams harnessed with marking crayons to determine the conception date. Blood samples were obtained weekly by venipuncture during the period of gestation, and all the plasma samples were stored at -20°C until assayed. The ewes were further divided on the basis of the number of lambs born into singleton pregnancy (SG; n = 5) or twin pregnancy (BB and TG; n = 5) groups to determine whether there are any FecB-specific differences in progesterone, follistatin, and FSH during pregnancy or whether the differences were related to litter size. Some BB ewes had litters of >2, but these ewes were not included in the study because of small sample size. All experiments were approved by the University of New England Animal Ethics Committee and conform to the NHMRC/CSIRO/AAC Code of Practice for the Care and Use of Animals for Experimental Purposes.

Hormone Assays

Follistatin was determined in plasma using an assay as previously described [28]. The assay included a rabbit antiserum (204; donated by D.M. deKretser, Institute of Reproduction & Development, Monash University, Clayton, VIC, Australia) raised against purified 35-kDa bovine follistatin. A human recombinant follistatin (FS288) was used as both standard and tracer. The dissociation reagents were modified to 10% Triton X-100, 3% sodium deoxycholate, and 0.5% SDS. Cross-reactivity with inhibin and activin was <0.5%. Plasma pools gave dose-response curves parallel to the standard curve, and the recovery of follistatin from spiked samples was 98% ± 5%. The detection limit was 1.5 ng/ml, and the intra- and interassay coefficients of variation were 6% and 18%, respectively.

Samples were assayed for progesterone using a procedure similar to that previously described [29]. The antiserum was prepared using progesterone-11{alpha}-HS-BSA (230; Bioquest Limited, North Ryde, NSW, Australia). Each sample was extracted in duplicate with a 10x volume of diethyl ether. The sensitivity of the assay was 25 pg/ml. The interassay variation was 11%, and the intra-assay variation was 4%.

FSH was measured using an RIA kit from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The detection limit of the assay was 0.8 ng/ml (oFSH NIDDK-RP-1), the interassay variation was 9%, and the intra-assay variation was 3%.

Data Analysis

The concentrations of progesterone, follistatin, and FSH across the estrous cycle and pregnancy and between BB and ++ ewes were analyzed as repeated measures and fitted to a generalized linear mixed model, with systematic effects of group and time, random effects of animal, and an animal by time interaction. Exploratory data plots indicated that the error should be modeled by a gamma distribution, and the log-link function was used. Trends over time in both the systematic and random models were represented by spline curves whose smoothness is regulated by the correlations among the residuals. The models were fit to the data using the ASREML statistical software [30]. The results are presented as weighted smooth splines of group trends, and the observed group means were plotted at each sampling time.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Estrous Cycle

The mean concentrations of progesterone, follistatin, and FSH based on samples taken daily throughout a natural estrous cycle are shown in Figures 1–3. Progesterone in both BB and ++ ewes, as expected, increased rapidly in the first week, plateaued through the second week, and then fell rapidly in the follicular phase from Day 14 to Day 17. In the BB ewes, progesterone began increasing earlier than in the ++ ewes, but in both groups progesterone began declining at the end of the luteal phase at the same time. The progesterone concentrations tended to be higher during the luteal phase and were significantly higher (P < 0.05) in BB ewes than in ++ ewes during the early luteal phase from Day 1 to Day 4, but they were not different during the follicular phase (Fig. 1). Follistatin fluctuated across the estrous cycle without significant change with time either in BB or in ++ ewes (Fig. 2). The overall concentrations were 11.22 ± 2.11 ng/ml for BB ewes and 11.86 ± 1.89 ng/ml for ++ ewes. FSH concentrations were higher in BB than in ++ ewes during the estrous cycle on most days (Fig. 3). In both groups, FSH was highest on the day of estrus, but in the BB ewes the peak was relatively higher and broader than that in the ++ ewes.



View larger version (42K):
[in this window]
[in a new window]
  		FIG. 1. Concentration and 95% confidence intervals of progesterone in plasma samples across the estrous cycle of Merino ewes previously segregated as homozygous for (open circle, n = 5) and noncarriers of (open triangle, n = 5) the Booroola major gene (FecB). Day 0 is the day of estrus as indicated by marking from a wether with a marking harness



View larger version (53K):
[in this window]
[in a new window]
  		FIG. 3. Concentration and 95% confidence intervals of FSH in plasma samples across the estrous cycle of Merino ewes previously segregated as homozygous for (open circle, n = 5) and noncarriers of (open triangle, n = 5) the Booroola major gene (FecB). Day 0 is the day of estrus as indicated by marking from a wether with a marking harness



View larger version (68K):
[in this window]
[in a new window]
  		FIG. 2. Concentration and 95% confidence intervals of follistatin in plasma samples across the estrous cycle of Merino ewes previously segregated as homozygous for (open circle, n = 5) and noncarriers of (open triangle, n = 5) the Booroola major gene (FecB). Day 0 is the day of estrus as indicated by marking from a wether with a marking harness

Pregnancy

In this study, the average (±SD) gestation periods were 149.1 ± 2.0 days for BB ewes, 149.8 ± 2.49 days for the singleton ++ group (SG), and 150.4 ± 1.14 days for the twin ++ group (TG) and were not significantly different among groups (P > 0.05).

The profiles of maternal plasma progesterone, follistatin, and FSH across gestation are shown in Figures 4–6. The concentrations of progesterone in BB ewes (Fig. 4) increased from 3.8 ± 0.4 ng/ml to a peak of 7.1 ± 0.5 ng/ml at 105 days of gestation. In ++ ewes (Fig. 4), progesterone concentrations were not different across gestation between the SG and TG groups. Progesterone in the ++ ewes increased from 1.9 ± 0.4 ng/ml in the SG and TG groups to a peak of 7.9 ± 0.8 ng/ml at Day 105. Progesterone concentrations in plasma tended to be higher in the BB ewes for the first half of pregnancy and then were not significantly different from those in the ++ ewes for the remaining period of gestation.



View larger version (25K):
[in this window]
[in a new window]
  		FIG. 4. Concentration and 95% confidence intervals of progesterone in plasma samples across gestation of Merino ewes previously segregated as homozygous for (BB) and noncarriers of the Booroola major gene and giving birth to twins (TG) or a singleton (SG)



View larger version (23K):
[in this window]
[in a new window]
  		FIG. 6. Concentration and 95% confidence intervals of FSH in plasma samples across gestation of Merino ewes previously segregated as homozygous for (BB) and noncarriers of the Booroola major gene and giving birth to twins (TG) or a singleton (SG)

The trend in follistatin concentrations differed between groups across gestation (Fig. 5). The trend in follistatin concentrations in BB ewes was to remain unchanged, with large confidence intervals due to the variation in trends between animals in the group. Follistatin increased in two ewes over the 21 wk, remained unchanged in one ewe, and decreased in two ewes. In the SG ++ ewes (Fig. 5), follistatin declined significantly from 10.65 ± 1.03 ng/ml on Day 55 to 6.81 ± 1.17 ng/ml at term. However, in the TG ++ ewes, follistatin concentrations remained unchanged across gestation, with an overall mean of 10.16 ± 0.75 ng/ml. As term approached, follistatin in the SG ++ ewes was significantly lower than that in the BB or TG ++ ewes.



View larger version (22K):
[in this window]
[in a new window]
  		FIG. 5. Concentration and 95% confidence intervals of follistatins in plasma samples across gestation of Merino ewes previously segregated as homozygous for (BB) and noncarriers of the Booroola major gene and giving birth to twins (TG) or a singleton (SG)

FSH concentrations declined during pregnancy, but with different profiles for each genotype (Fig. 6). In BB ewes, FSH tended to decline more rapidly earlier in pregnancy than in the ++ ewes, and lower concentrations were noted during mid gestation. FSH concentrations in both groups of ++ ewes (Fig. 6) were similar but declined more rapidly than those in BB ewes toward the end of pregnancy. In comparison with the ++ ewes, lower concentrations were observed in BB ewes from Day 69 to Day 97.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
We present the first reports of plasma profiles of progesterone, FSH, and follistatin in the prolific Australian Booroola strain of Merino sheep compared with those of its nonprolific counterpart across the estrous cycle and pregnancy. Plasma progesterone concentrations did not differ significantly between BB and ++ ewes during the follicular phase. However, on most of days in luteal phase, the progesterone concentrations were higher in BB ewes than in ++ ewes. These data contrast with previous reports that there were no FecB-specific differences in jugular plasma concentrations or ovarian secretion rates of progesterone in middle or late luteal phase and the prostaglandin F2{alpha}-induced follicular phase [13], although there were differences in the mean numbers of CL during the midluteal phase between the genotypes [7]. This inconsistency between the present and previous findings is likely to be due to the small windows of study used by other research groups.

Booroola ewes are reported to ovulate about 7.5 h earlier than the ordinary Merino after the onset of estrus. No differences have been noted in the time from the onset of estrus to the preovulatory LH surge nor in the duration of the preovulatory LH surge itself [31]. These findings suggest that the early increase in progesterone during the luteal phase may be due at least in part to the earlier development of the CL. However, this explanation does not account fully for the rise occurring nearly 2 days early, which is likely due to the impairment of the BMP 1B receptor [5], reducing the dampening effect of BMPs on progesterone production by granulosa cells in the maturing follicles.

The development of immunoassays for follistatin has been complicated by the characteristics of this molecule, such as presence of multiple molecular forms in biological fluids in a variety of species, varying degrees of glycosylation, and the existence of complexes of follistatin with activins and perhaps other growth factors. There is no widely accepted follistatin assay, and a number of different immunoassays have been reported using different standards and antibodies. In these assays, some researchers have used human recombinant FS288 or FS315 as standards, and others have used purified individual porcine or bovine isoforms or mixtures of these isoforms [27, 28]. Therefore, it is impossible to fully reconcile all the data emerging from studies in which these various assays have been used.

Gilfillan and Robertson [32] reported that during the human menstrual cycle there were significantly lower total serum follistatin concentrations during the luteal phase than during the follicular phase. In contrast, others have found no significant variation across the human menstrual cycle [33, 27]. In the Klein et al. study of the estrous cycle in sheep [22], a significant increase in plasma follistatin concentrations was observed between Day 4 and Days 10–11 after the LH surge, and this increase was followed by a gradual decrease between Day 11 and Day 3 of the follicular phase of the next cycle. However, the assay used in that study was later found to be significantly affected by the presence of activin [23], which in the light of our study suggests that the rise in follistatin observed by Klein et al. [22] was likely a reflection of changes in activin concentrations.

In the present study, follistatin concentrations remained unchanged throughout the estrous cycle in BB and ++ ewes. Based on the results of the present and most previous studies, it is clear that the gonads are not a major source of circulating follistatin, and peripheral plasma follistatin concentrations are not an indicator of cyclic ovarian activity. Therefore, we concluded that follistatin during the estrous cycle is not affected by the presence of the FecB gene.

During pregnancy, major differences were observed between BB and ++ ewes that could not be accounted for by the increased number of fetuses. The concentrations of progesterone increased across gestation in both genotypes, with the pregnancy increase in progesterone occurring much earlier in BB ewes that in either of the ++ groups. This finding and the estrous data strongly suggest that progesterone concentrations are influenced by the FecB gene, which implicates BMPs as having an important role in pregnancy. Maternal plasma concentrations of follistatin remained unchanged in the BB and TG ++ ewes during gestation, in contrast to the decline observed in the SG ++ ewes. However, the high level of variability between animals in the BB group warrants further study. Although these ewes gave birth only to twins, their high ovulation rate suggests that other fetuses died at various stages of development, consequently complicating the follistatin profiles. Nevertheless, the different profiles in maternal follistatin observed between the BB ewes and ++ ewes may be due to the number of fetuses and may be independent of the FecB gene. FSH concentrations, as expected, declined across gestation in all three groups. However, FSH declined more rapidly during midgestation in the BB group than in the ++ groups. The higher concentrations of FSH observed during the estrous cycle and the differences in FSH secretion during pregnancy in BB ewes compared with ++ ewes lead us to conclude that FSH secretion is influenced by the FecB gene.

The gene-specific profiles in maternal plasma progesterone could reflect differences in the number and maturity of CL during early pregnancy. At the beginning of pregnancy, the number of CL is likely to be higher and the CL develop more quickly in BB than in ++ ewes. Progesterone concentrations in BB ewes on Day 6 were already similar to those during the normal luteal phase, but they did not reach equivalent levels until Day 20 in ++ ewes.

In SG ++ ewes, follistatin fell significantly between Day 55 and Day 76 while progesterone started increasing. In the study of Knight et al. [34], inhibin A fell about 7-fold between Day 60 and Day 90 of gestation in crossbred ewes. Thus, many endocrine events occur in the transition from the corpus luteum-dependent phase in early gestation to the placenta-dependent phase in late gestation.

Our findings concerning the follistatin profiles in Booroola or ordinary Merino ewes contrast with those associated with human pregnancy, during which circulating follistatin is greatly increased in the third trimester. Inhibin A profiles during gestation were also different between sheep and humans, with inhibin A concentrations declining in ewes [34] but increasing in humans across gestation [35]. These data suggest that activins/inhibins are differently regulated in sheep and humans.


   ACKNOWLEDGMENTS
 
The authors thank G. Chaffey and B. Cross for their technical assistance in blood sample collection and RIA.


   FOOTNOTES
 
1 This work was supported by the Kent Hughes Foundation and the National Health and Medical Research Council of Australia. Back

2 Correspondence: J.R. McFarlane, Department of Physiology, University of New England, Armidale, NSW 2351 Australia. FAX: 61 2 6773 3234; jmcfarla{at}metz.une.edu.au Back

Received: 21 March 2002.

First decision: 20 April 2003.

Accepted: 9 April 2003.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Piper L, Bindon BM. Genetic segregation for fecundity in Booroola Merino sheep. In: Barton RA, Smith WC (eds.), Proceedings of the World Congress on Sheep and Beef Cattle Breeding, 1. Palmerston North, New Zealand: Dunmore Press; 1982: 395–400
  2. Davis GH, Montgomery GW, Allison AJ, Kelly RW, Bray AR. Segregation of a major gene influencing fecundity in progeny of Booroola in New Zealand. N Z J Agric Res 1982 25:525-529
  3. Wilson T, Wu XY, Juengel JL, Ross IK, Lumsden JM, Lord EA, Dodds KG, Walling GA, McEwan JC, O'Connell AR, McNatty KP, Montgomery GW. Highly prolific Booroola sheep have a mutation in the intracellular kinase domain of bone morphogenetic protein IB receptor (ALK-6) that is expressed in both oocytes and granulosa cells. Biol Reprod 2001 64:1225-1235[Abstract/Free Full Text]
  4. Souza CJ, MacDougall C, Campbell BK, McNeilly AS, Baird DT. The Booroola (FecB) phenotype is associated with a mutation in the bone morphogenetic receptor type 1 B (BMPR1B) gene. J Endocrinol 2001 169:R1-R6[Abstract]
  5. Mulsant P, Lecerf F, Fabre S, Schibler L, Monget P, Lanneluc I, Pisselet C, Riquet J, Monniaux D, Callebaut I, Cribiu E, Thimonier J, Teyssier J, Bodin L, Cognie Y, Chitour N, Elsen JM. Mutation in bone morphogenetic protein receptor-IB is associated with increased ovulation rate in Booroola Merino ewes. Proc Natl Acad Sci U S A 2001 98:5104-5109[Abstract/Free Full Text]
  6. Souza CJH, Moraes JCF, Chagas LM. Effect of the Booroola gene on time of ovulation and ovulatory dynamics. Anim Reprod Sci 1994 37:7-13
  7. McNatty KP, Lun S, Heath DA, Ball K, Smith P, Hudson NL, McDiarmid J, Gibb M, Henderson KM. Differences in ovarian activity between Booroola x Merino ewes which were homozygous, heterozygous and non-carrier of a major gene influencing their ovulation rate. J Reprod Fertil 1986 77:193-205[Abstract/Free Full Text]
  8. McNatty KP, Fisher M, Collins F, Hudson NL, Heath DA, Ball K, Henderson KM. Differences in plasma concentrations of FSH and LH in ovariectomized Booroola FF and ++ ewes. J Reprod Fertil 1989 85:705-713[Abstract/Free Full Text]
  9. Fleming JS, Tisdall DJ, Greenwood PJ, Hudson NL, Heath DA, McNatty KP. Expression of the genes for {alpha} inhibin, ßA inhibin and follistatin in the ovaries of Booroola ewes which were homozygotes or non-carriers of the fecundity gene FecB. J Mol Endocrinol 8:265–273
  10. Montgomery GW, McNatty KP, Davis GH. Physiology and molecular genetics of mutations that increase ovulation rate in sheep. Endocr Rev 1992 13:309-328[Abstract/Free Full Text]
  11. Scaramuzzi RJ, Radford HM. Factors regulating ovulation rate in the ewe. J Reprod Fertil 1983 69:353-367[Abstract/Free Full Text]
  12. Bindon BM. Reproductive biology of the Booroola Merino sheep. Aust J Biol Sci 1984 37:163-189[Medline]
  13. Souza CJH, Campbell BK, Webb R, Baird DT. Secretion of inhibin A and follicular dynamics throughout the estrous cycle in the sheep with and without the Booroola gene (FecB). Endocrinology 1997 138:5333-5340[Abstract/Free Full Text]
  14. McNatty KP, Heath DA, Hudson NL, Ball K, Condell L. Concentrations of immunoreative inhibin in ovarian and peripheral venous plasma and follicular fluid of Booroola ewes that are homozygous carriers or non-carriers of the FecB gene. J Reprod Fertil 1992 95:489-502[Abstract/Free Full Text]
  15. McNatty KP, Hudson NL, Collins F, Fisher M, Heath DA, Henderson KM. Effects of oestradiol-17ß, progesterone or bovine follicular fluid on the plasma concentrations of FSH and LH in ovariectomied Booroola ewes which were homozygous carriers or non-carriers of a fecundity. J Reprod Fertil 1989 87:573-585[Abstract/Free Full Text]
  16. Robertson DM, Klein R, de Vos FL, McLachlan RI, Wettenhall REH, Hearn MTW, Burger HG, de Kretser DM. The isolation of polypeptides with FSH suppressing activity from bovine follicular fluid which are structurally different to inhibin. Biochem Biophys Res Commun 1987 149:744-749[CrossRef][Medline]
  17. Ueno N, Ling N, Ying SY, Esch F, Shimasaki S, Guillemin R. Isolation and partial characterization of follistatin: a single-chain Mr 35 000 monomeric protein that inhibits the release of follicle-stimulating hormone. Proc Natl Acad Sci U S A 1987 84:8282-8286[Abstract/Free Full Text]
  18. Mather JP, Roberts PE, Krummen LA. Follistatin modulates activin activity in a cell- and tissue-specific manner. Endocrinology 1993 232:2732-2734
  19. Nakamura T, Takio K, Eto Y, Shibai K, Sugino H. Activin-binding protein from rat ovary is follistatin. Science 1990 247:836-838[Abstract/Free Full Text]
  20. Winter JP, ten Dijke P, de Vries CJM, van Achterberg TAE, Sugino H, de Waele P, Huylebroeck D, Verschueren K, van den Eijnden-van Raaij AJM. Follistatins neutralize activin bioactivity by inhibition of activin binding to its type II receptors. Mol Cell Endocrinol 1996 116:105-114[CrossRef][Medline]
  21. Iemura S, Yamamoto TS, Takagi C, Uchiyama H, Natsume T, Shimasaki S, Sugino H, Ueno N. Direct binding of follistatin to a complex of bone-morphogenetic protein and its receptor inhibits ventral and epidermal cell fates in early Xenopus embryo. Proc Natl Acad Sci U S A 1998 95:9337-9342[Abstract/Free Full Text]
  22. Klein R, Findlay JK, Clarke IJ, de Kretser DM, Robertson DM. Radioimmunoassay of FSH-suppressing protein in the ewe: concentrations during the oestrous cycle and following ovariectomy. J Endocrinol 1993 137:433-443[Abstract/Free Full Text]
  23. de Kretser DM, Foulds LM, Hancock M, Robertson DM. Partial characterization of inhibin, activin, and follistatin in the term human placenta. J Clin Endocrinol Metab 1994 79:502-507[Abstract]
  24. Tisdall DJ, Hill DF, Petersen GB, Fleming JS. Ovine follistatin: characterization of cDNA and expression in sheep ovary during the luteal phase of the oestrous cycle. J Mol Endocrinol 1992 8:259-264[Abstract/Free Full Text]
  25. Tisdall DJ, Hudson N, Smith P, McNatty KP. Localization of ovine follistatin and {alpha} and ßA inhibin mRNA in the sheep ovary during the oestrous cycle. J Mol Endocrinol 1994 12:181-193[Abstract/Free Full Text]
  26. Wakatsuki M, Shintani Y, Abe M, Liu ZH, Shitsukawa K, Saito S. Immunoradiometric assay for follistatin: serum immunoreactive follistatin levels in normal adults and pregnant women. J Clin Endocrinol 1996 81:630-634[Abstract]
  27. Evans LW, Muttukrishna S, Groome NP. Development, validation and application of an ultra-sensitive two-site enzyme immunoassay for human follistatin. J Endocrinol 1998 156:275-282[Abstract]
  28. O'Connor AE, McFarlane JR, Hayward S, Yohksichiya T, Groome NP, de Kretser DM. Serum activin A and follistatin concentrations during human pregnancy: a cross-sectional and longitudinal study. Hum Reprod 1999 14:827-832[Abstract/Free Full Text]
  29. McFarlane JR, Carrick FN, Gemmell RT, MacDonald B. Seasonal effects on androgen secretion in the male bandicoot, Isoodon macrourus. In: Seebeck JH, Brown PR, Wallis Rh, Kemper CM (eds.), Bandicoots Bilbies. Sydney, Australia: Beatty & Sons; 1990:251–257
  30. Gilmour AR, Cullis BR, Welham S, Thompson R. ASREML-NSW Agriculture Biometrics Technical Bulletin. Orange, Australia: New South Wales Department of Agriculture; 1998
  31. Bindon BM, Piper LR, Thimonier J. Preovulatory LH characteristics and time of ovulation in the prolific Booroola Merino ewe. J Reprod Fertil 1984 71:519-523[Abstract/Free Full Text]
  32. Gilfillan CP, Robertson DM. Development and validation of a radioimmunoassay for follistatin in human serum. Clin Endocrinol (Oxf) 1994 41:453-461[Medline]
  33. Khoury RH, Wang QF, Crowley WF, Hall JE, Schneyer AL, Toth T, Midgley AR, Sluss PM. Serum follistatin levels in women: evidence against an endocrine function of ovarian follistatin. J Clin Endocrinol Metab 1995 80:1361-1368[Abstract]
  34. Knight PG, Feist SA, Tannetta DS, Bleach EC, Fowler PA, O'Brien M, Groome NP. Measurement of inhibin-A({alpha}ßA dimer) during the oestrous cycle, after manipulation of ovarian activity and during pregnancy in ewes. J Reprod Fertil 1988 113:159-166
  35. Muttukrishna S, George L, Fowler PA, Groome NP, Knight PG. Measurement of serum concentrations of inhibin-A({alpha}ßA dimer) during human pregnancy. Clin Endocrinol (Oxf) 1995 42:391-397[Medline]




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
69/3/1079    most recent
biolreprod.102.005512v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow My Folders
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Xia, Y.
Right arrow Articles by McFarlane, J.R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xia, Y.
Right arrow Articles by McFarlane, J.R.
Agricola
Right arrow Articles by Xia, Y.
Right arrow Articles by McFarlane, J.R.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS