Preantral follicle numbers and size in heifers carrying Trio, a bovine high fecundity allele

in Reproduction
Authors:
James V ConstantinoDepartment of Animal Sciences, The Ohio State University, Columbus, Ohio, USA

Search for other papers by James V Constantino in
Current site
Google Scholar
PubMed
Close
,
Ana Carranza-MartinDepartment of Animal Sciences, The Ohio State University, Columbus, Ohio, USA

Search for other papers by Ana Carranza-Martin in
Current site
Google Scholar
PubMed
Close
,
Christopher PremanandanDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA

Search for other papers by Christopher Premanandan in
Current site
Google Scholar
PubMed
Close
,
Brian W KirkpatrickDepartment of Animal & Dairy Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA

Search for other papers by Brian W Kirkpatrick in
Current site
Google Scholar
PubMed
Close
,
Milo C WiltbankDepartment of Animal & Dairy Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA

Search for other papers by Milo C Wiltbank in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0001-8188-0991
, and
Alvaro Garcia-GuerraDepartment of Animal Sciences, The Ohio State University, Columbus, Ohio, USA

Search for other papers by Alvaro Garcia-Guerra in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0002-4114-5965
View More View Less

Correspondence should be addressed to A García-Guerra; Email: garciaguerra.1@osu.edu

*(JV Constantino and A Carrana-Martin contributed equally as first authors)

Restricted access

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $1.00
USD  $1.00

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $1.00
USD  $1.00

USD  $1.00
USD  $1.00

In brief

The bovine high fecundity allele, Trio, results in the occurrence of multiple ovulations and is characterized by antral follicles that develop slower and acquire ovulatory capacity at smaller sizes. This study provides novel information on the effect of the Trio allele on early folliculogenesis.

Abstract

The bovine high fecundity allele, Trio, causes overexpression in granulosa cells (GCs) of SMAD6, an inhibitor of BMP15-activated SMAD signalling. Furthermore, the Trio allele results in antral follicles that develop slower, acquire ovulatory capacity at smaller sizes, and have three-fold greater ovulation rate compared to half-sib non-carriers. The present study was designed to determine preantral follicle numbers and size in Trio carrier and non-carrier cattle testing the hypothesis that inhibition of SMAD signalling would alter preantral follicle activation and/or growth. Ovarian tissues from Trio carrier (n = 12) and non-carrier (n = 12) heifers were obtained by laparotomy after follicle wave synchronization. Follicle numbers and dimensions were determined for each stage of development (primordial, transitional, primary, and secondary) from paraffin-embedded sections. There were no differences in the number of primordial, transitional, or secondary follicles or in antral follicle count, circulating AMH, or ovarian volume between carriers and non-carriers. Trio carriers had ~2.5-fold greater (P < 0.01) number of primary follicles than non-carriers, and transitional and primary follicles were larger (~1.2-fold; P < 0.1) in Trio carriers. Oocyte volume of primordial and transitional follicles was not different between genotypes; however, oocytes were larger (P < 0.05) in primary (~1.3-fold) and secondary (~1.8-fold) follicles for Trio carriers. Granulosa cell numbers were not different (P > 0.3) between carriers and non-carriers, irrespective of the stage of development. These results suggest that, after primordial follicle activation, follicles in Trio carrier cattle have slower progression through the primary stage, hence the larger oocyte and greater number of primary follicles.

 

  • Collapse
  • Expand
  • Adhikari D & & Liu K 2009 Molecular mechanisms underlying the activation of mammalian primordial follicles. Endocrine Reviews 30 438464. (https://doi.org/10.1210/er.2008-0048)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Arias J & & Kirkpatrick B 2004 Mapping of bovine ovulation rate QTL; an analytical approach for three generation pedigrees. Animal Genetics 35 713. (https://doi.org/10.1046/j.1365-2052.2003.01069.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bodensteiner KJ, Clay CM, Moeller CL & & Sawyer HR 1999 Molecular cloning of the ovine growth/differentiation Factor-9 gene and expression of growth/differentiation Factor-9 in ovine and bovine Ovaries1. Biology of Reproduction 60 381386. (https://doi.org/10.1095/biolreprod60.2.381)

    • Search Google Scholar
    • Export Citation
  • Bodin L, Pasquale ED, Fabre S, Bontoux M, Monget P, Persani L & & Mulsant P 2007 A novel mutation in the Bone Morphogenetic Protein 15 gene causing defective protein secretion is associated with both increased ovulation rate and sterility in Lacaune sheep. Endocrinology 148 393400. (https://doi.org/10.1210/en.2006-0764)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Braw-Tal R & & Yossefi S 1997 Studies in vivo and in vitro on the initiation of follicle growth in the bovine ovary. Journal of Reproduction and Fertility 109 165171. (https://doi.org/10.1530/jrf.0.1090165)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Braw-Tal R, McNatty KP, Smith P, Heath DA, Hudson NL, Phillips DJ, McLeod BJ & & Davis GH 1993 Ovaries of ewes homozygous for the X-linked Inverdale gene (FecXI) are devoid of secondary and tertiary follicles but contain many abnormal structures. Biology of Reproduction 49 895907. (https://doi.org/10.1095/biolreprod49.5.895)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cahill LP & & Mauléon P 1981 A study of the population of primordial and small follicles in the sheep. Journal of Reproduction and Fertility 61 201206. (https://doi.org/10.1530/jrf.0.0610201)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cahill LP, Mariana JC & & Mauleon P 1979 Total follicular populations in ewes of high and low ovulation rates. Journal of Reproduction and Fertility 55 2736. (https://doi.org/10.1530/jrf.0.0550027)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Celestino JJH, Lima-Verde IB, Bruno JB, Matos MHT, Chaves RN, Saraiva MV, Silva CMG, Faustino LR, Rossetto R & Lopes CAP et al.2011 Steady-state level of bone morphogenetic protein-15 in goat ovaries and its influence on in vitro development and survival of preantral follicles. Molecular and Cellular Endocrinology 338 19. (https://doi.org/10.1016/j.mce.2011.02.007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cognie Y, Benoit F, Poulin N, Khatir H & & Driancourt MA 1998 Effect of follicle size and of the FecB Booroola gene on oocyte function in sheep. Journal of Reproduction and Fertility 112 379386. (https://doi.org/10.1530/jrf.0.1120379)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cushman RA, Hedgpeth VS, Echternkamp SE & & Britt JH 2000 Evaluation of numbers of microscopic and macroscopic follicles in cattle selected for twinning. Journal of Animal Science 78 15641567. (https://doi.org/10.2527/2000.7861564x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Davis GH, Balakrishnan L, Ross IK, Wilson T, Galloway SM, Lumsden BM, Hanrahan JP, Mullen M, Mao XZ & Wang GL et al.2006 Investigation of the Booroola (FecB) and Inverdale (FecX(I)) mutations in 21 prolific breeds and strains of sheep sampled in 13 countries. Animal Reproduction Science 92 8796. (https://doi.org/10.1016/j.anireprosci.2005.06.001)

    • Search Google Scholar
    • Export Citation
  • Domingues RR, Andrade FS, Paulo N Andrade J, Moghbeli SM, Gomez-Leon V, Madureira G, Mello MRB, Kirkpatrick BW & & Wiltbank MC 2023 SMAD6 inhibits granulosa cell proliferation and follicle growth rate in carrier and noncarrier heifers of the Trio allele. Reproduction 165 269279. (https://doi.org/10.1530/REP-22-0232)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N & & Matzuk MM 1996 Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 383 531535. (https://doi.org/10.1038/383531a0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Driancourt MA, Cahill LP & & Bindon BM 1985 Ovarian follicular populations and preovulatory enlargement in Booroola and control Merino ewes. Journal of Reproduction and Fertility 73 93107. (https://doi.org/10.1530/jrf.0.0730093)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Drouilhet L, Taragnat C, Fontaine J, Duittoz A, Mulsant P, Bodin L & & Fabre S 2010 Endocrine characterization of the reproductive axis in highly prolific lacaune sheep homozygous for the FecLL mutation. Biology of Reproduction 82 815824. (https://doi.org/10.1095/biolreprod.109.082065)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Estienne A, Pierre A, di Clemente N, Picard JY, Jarrier P, Mansanet C, Monniaux D & & Fabre S 2015 Anti-Mullerian hormone regulation by the Bone Morphogenetic Proteins in the sheep ovary: deciphering a direct regulatory pathway. Endocrinology 156 301313. (https://doi.org/10.1210/en.2014-1551)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fair T, Hulshof SC, Hyttel P, Greve T & & Boland M 1997 Oocyte ultrastructure in bovine primordial to early tertiary follicles. Anatomy and Embryology 195 327336. (https://doi.org/10.1007/s004290050052)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fenwick MA, Mora JM, Mansour YT, Baithun C, Franks S & & Hardy K 2013 Investigations of TGF-β signaling in preantral follicles of female mice reveal differential roles for bone morphogenetic Protein 15. Endocrinology 154 34233436. (https://doi.org/10.1210/en.2012-2251)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Figueiredo JR, Hulshof SCJ, Van den Hurk R, Bevers MM, Thiry M, Nusgens B & & Beckers JF 1994 The physiological status of the ovarian donor affects in vitro development of isolated bovine preantral follicles. Theriogenology 42 13031310. (https://doi.org/10.1016/0093-691X(9490250-M)

    • Search Google Scholar
    • Export Citation
  • García-Guerra A, Kirkpatrick BW & & Wiltbank MC 2017a Follicular waves and hormonal profiles during the estrous cycle of carriers and non-carriers of the Trio allele, a major bovine gene for high ovulation and fecundity. Theriogenology 100 100113. (https://doi.org/10.1016/j.theriogenology.2017.05.029)

    • Search Google Scholar
    • Export Citation
  • García-Guerra A, Motta JCL, Melo LF, Kirkpatrick BW & & Wiltbank MC 2017b Ovulation rate, antral follicle count, and circulating anti-Müllerian hormone in Trio allele carriers, a novel high fecundity bovine genotype. Theriogenology 101 8190. (https://doi.org/10.1016/j.theriogenology.2017.05.026)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • García-Guerra A, Canavessi AMO, Monteiro PLJ, Mezera MA, Sartori R, Kirkpatrick BW & & Wiltbank MC 2018a Trio, a novel high fecundity allele: III. Acquisition of dominance and ovulatory capacity at a smaller follicle size. Biology of Reproduction 98 350365. (https://doi.org/10.1093/biolre/iox157)

    • Search Google Scholar
    • Export Citation
  • García-Guerra A, Kamalludin MH, Kirkpatrick BW & & Wiltbank MC 2018b Trio, a bovine high fecundity allele: II. Hormonal profile and follicular dynamics underlying the high ovulation rate. Biology of Reproduction 98 335349. (https://doi.org/10.1093/biolre/iox156)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • García-Guerra A, Wiltbank MC, Battista SE, Kirkpatrick BW & & Sartori R 2018c Mechanisms regulating follicle selection in ruminants: lessons learned from multiple ovulation models. Animal Reproduction 15(Supplement 1) 660679. (https://doi.org/10.21451/1984-3143-AR2018-0027)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hanrahan JP, Gregan SM, Mulsant P, Mullen M, Davis GH, Powell R & & Galloway SM 2004 Mutations in the genes for oocyte-derived growth factors GDF9 and BMP15 are associated with both increased ovulation rate and sterility in Cambridge and Belclare sheep (Ovis aries). Biology of Reproduction 70 900909. (https://doi.org/10.1095/biolreprod.103.023093)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hata A, Lagna G, Massague J & & Hemmati-Brivanlou A 1998 Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor. Genes and Development 12 186197. (https://doi.org/10.1101/gad.12.2.186)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Henderson KM, McNatty KP, Okeeffe LE, Lun S, Heath DA & & Prisk MD 1987 Differences in gonadotropin-stimulated cyclic-AMP production by granulosa-cells from Booroola x Merino ewes which were homozygous, heterozygous or noncarriers of a fecundity gene influencing their ovulation rate. Journal of Reproduction and Fertility 81 395402. (https://doi.org/10.1530/jrf.0.0810395)

    • Search Google Scholar
    • Export Citation
  • Hosoe M, Kaneyama K, Ushizawa K, Hayashi KG & & Takahashi T 2011 Quantitative analysis of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) gene expression in calf and adult bovine ovaries. Reproductive Biology and Endocrinology: RB&E 9 3333. (https://doi.org/10.1186/1477-7827-9-33)

    • Search Google Scholar
    • Export Citation
  • Hsueh AJ, Kawamura K, Cheng Y & & Fauser BC 2015 Intraovarian control of early folliculogenesis. Endocrine Reviews 36 124. (https://doi.org/10.1210/er.2014-1020)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ireland JLH, Scheetz D, Jimenez-Krassel F, Themmen AP, Ward F, Lonergan P, Smith GW, Perez GI, Evans AC & & Ireland JJ 2008 Antral follicle count reliably predicts number of morphologically healthy oocytes and follicles in ovaries of young adult cattle. Biology of Reproduction 79 12191225. (https://doi.org/10.1095/biolreprod.108.071670)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ishisaki A, Yamato K, Hashimoto S, Nakao A, Tamaki K, Nonaka K, ten Dijke P, Sugino H & & Nishihara T 1999 Differential inhibition of Smad6 and Smad7 on bone morphogenetic protein- and activin-mediated growth arrest and apoptosis in B cells. Journal of Biological Chemistry 274 1363713642. (https://doi.org/10.1074/jbc.274.19.13637)

    • Search Google Scholar
    • Export Citation
  • Juengel JL, Hudson NL, Berg M, Hamel K, Smith P, Lawrence SB, Whiting L & & McNatty KP 2009 Effects of active immunization against growth differentiation factor 9 and/or bone morphogenetic protein 15 on ovarian function in cattle. Reproduction 138 107114. (https://doi.org/10.1530/REP-09-0009)

    • Search Google Scholar
    • Export Citation
  • Juengel JL, Davis GH & & McNatty KP 2013 Using sheep lines with mutations in single genes to better understand ovarian function. Reproduction 146 R111R123. (https://doi.org/10.1530/REP-12-0509)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kamalludin MH, Garcia-Guerra A, Wiltbank MC & & Kirkpatrick BW 2018 Trio, a novel high fecundity allele: I. Transcriptome analysis of granulosa cells from carriers and non-carriers of a major gene for bovine ovulation rate. Biology of Reproduction 98 323334. (https://doi.org/10.1093/biolre/iox133)

    • Search Google Scholar
    • Export Citation
  • Kirkpatrick BW & & Morris CA 2015 A major gene for bovine ovulation rate. PLoS One 10 e0129025. (https://doi.org/10.1371/journal.pone.0129025)

    • Search Google Scholar
    • Export Citation
  • Kirkpatrick BW, Byla BM & & Gregory KE 2000 Mapping quantitative trait loci for bovine ovulation rate. Mammalian Genome 11 136139. (https://doi.org/10.1007/s003350010026)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Knight PG & & Glister C 2006 TGF-β superfamily members and ovarian follicle development. Reproduction 132 191206. (https://doi.org/10.1530/rep.1.01074)

  • Kona SS, Praveen Chakravarthi V, Siva Kumar AV, Srividya D, Padmaja K & & Rao VH 2016 Quantitative expression patterns of GDF9 and BMP15 genes in sheep ovarian follicles grown in vivo or cultured in vitro. Theriogenology 85 315322. (https://doi.org/10.1016/j.theriogenology.2015.09.022)

    • Search Google Scholar
    • Export Citation
  • Lahoz B, Alabart JL, Folch J, Sánchez P, Echegoyen E & & Cocero MJ 2013 Influence of the FecXR allele in heterozygous ewes on follicular population and outcomes of IVP and ET using LOPU-derived oocytes. Reproduction in Domestic Animals 48 717723. (https://doi.org/10.1111/rda.12150)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Laissue P, Christin-Maitre S, Touraine P, Kuttenn F, Ritvos O, Aittomaki K, Bourcigaux N, Jacquesson L, Bouchard P & Frydman R et al.2006 Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure. European Journal of Endocrinology 154 7 397 44. (https://doi.org/10.1530/eje.1.02135)

    • Search Google Scholar
    • Export Citation
  • Lassoued N, Benkhlil Z, Woloszyn F, Rejeb A, Aouina M, Rekik M, Fabre S & & Bedhiaf-Romdhani S 2017 FecX (Bar) a Novel BMP15 mutation responsible for prolificacy and female sterility in Tunisian Barbarine Sheep. BMC Genetics 18 43. (https://doi.org/10.1186/s12863-017-0510-x)

    • Search Google Scholar
    • Export Citation
  • Li Q 2015 Inhibitory SMADs: potential regulators of ovarian function. Biology of Reproduction 92 50. (https://doi.org/10.1095/biolreprod.114.125203)

  • Li Q, Rajanahally S, Edson MA & & Matzuk MM 2009 Stable expression and characterization of N-terminal tagged recombinant human bone morphogenetic protein 15. Molecular Human Reproduction 15 779788. (https://doi.org/10.1093/molehr/gap062)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lima IMT, Brito IR, Rossetto R, Duarte AB, Rodrigues GQ, Saraiva MV, Costa JJN, Donato MA, Peixoto CA & Silva JRV et al.2012 BMPRIB and BMPRII mRNA expression levels in goat ovarian follicles and the in vitro effects of BMP-15 on preantral follicle development. Cell and Tissue Research 348 225238. (https://doi.org/10.1007/s00441-012-1361-4)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Martinez-Royo A, Jurado JJ, Smulders JP, Marti JI, Alabart JL, Roche A, Fantova E, Bodin L, Mulsant P & Serrano M et al.2008 A deletion in the bone morphogenetic protein 15 gene causes sterility and increased prolificacy in Rasa Aragonesa sheep. Animal Genetics 39 294297. (https://doi.org/10.1111/j.1365-2052.2008.01707.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Massagué J & & Wotton D 2000 Transcriptional control by the TGF-β/Smad signaling system. EMBO Journal 19 17451754. (https://doi.org/10.1093/emboj/19.8.1745)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • McNatty KP, Henderson KM, Lun S, Heath DA, Ball K, Hudson NL, Fannin J, Gibb M, Kieboom LE & & Smith P 1985 Ovarian activity in Booroola × Romney ewes which have a major gene influencing their ovulation rate. Journal of Reproduction and Fertility 73 109120. (https://doi.org/10.1530/jrf.0.0730109)

    • Search Google Scholar
    • Export Citation
  • McNatty KP, Kieboom LE, McDiarmid J, Heath DA & & Lun S 1986a Adenosine cyclic 3′,5′-monophosphate and steroid production by small ovarian follicles from Booroola ewes with and without a fecundity gene. Journal of Reproduction and Fertility 76 471480. (https://doi.org/10.1530/jrf.0.0760471)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • McNatty KP, Lun S, Heath DA, Ball K, Smith P, Hudson NL, McDiarmid J, Gibb M & & Henderson KM 1986b Differences in ovarian activity between Booroola × Merino ewes which were homozygous, heterozygous and non-carriers of a major gene influencing their ovulation rate. Journal of Reproduction and Fertility 77 193205. (https://doi.org/10.1530/jrf.0.0770193)

    • Search Google Scholar
    • Export Citation
  • McNatty KP, Juengel JL, Reader KL, Lun S, Myllymaa S, Lawrence SB, Western A, Meerasahib MF, Mottershead DG & Groome NP et al.2005 Bone morphogenetic protein 15 and growth differentiation factor 9 co-operate to regulate granulosa cell function in ruminants. Reproduction 129 481487. (https://doi.org/10.1530/rep.1.00517)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • McNatty KP, Hudson NL, Whiting L, Reader KL, Lun S, Western A, Heath DA, Smith P, Moore LG & & Juengel JL 2007 The effects of immunizing sheep with different BMP15 or GDF9 peptide sequences on ovarian follicular activity and ovulation rate. Biology of Reproduction 76 552560. (https://doi.org/10.1095/biolreprod.106.054361)

    • Search Google Scholar
    • Export Citation
  • McNatty KP, Heath DA, Hudson NL, Lun S, Juengel JL & & Moore LG 2009 Gonadotrophin-responsiveness of granulosa cells from bone morphogenetic protein 15 heterozygous mutant sheep. Reproduction 138 545551. (https://doi.org/10.1530/REP-09-0154)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • McNatty KP, Heath DA, Clark Z, Reader K, Juengel JL & & Pitman JL 2017 Ovarian characteristics in sheep with multiple fecundity genes. Reproduction 153 233240. (https://doi.org/10.1530/REP-16-0587)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Monniaux D 2016 Driving folliculogenesis by the oocyte-somatic cell dialog: lessons from genetic models. Theriogenology 86 4153. (https://doi.org/10.1016/j.theriogenology.2016.04.017)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mulsant P, Lecerf F, Fabre S, Schibler L, Monget P, Lanneluc I, Pisselet C, Riquet J, Monniaux D & Callebaut I et al.2001 Mutation in bone morphogenetic protein receptor-IB is associated with increased ovulation rate in Booroola Merino ewes. Proceedings of the National Academy of Sciences of the United States of America 98 51045109. (https://doi.org/10.1073/pnas.091577598)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nicol L, Bishop SC, Pong-Wong R, Bendixen C, Holm LE, Rhind SM & & McNeilly AS 2009 Homozygosity for a single base-pair mutation in the oocyte-specific GDF9 gene results in sterility in Thoka sheep. Reproduction 138 921933. (https://doi.org/10.1530/REP-09-0193)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Passos MJ, Vasconcelos GL, Silva AWB, Brito IR, Saraiva MV, Magalhães DM, Costa JJN, Donato MA, Ribeiro RP & Cunha EV et al.2013 Accelerated growth of bovine preantral follicles in vitro after stimulation with both FSH and BMP-15 is accompanied by ultrastructural changes and increased atresia. Theriogenology 79 12691277. (https://doi.org/10.1016/j.theriogenology.2013.02.023)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Peng J, Li Q, Wigglesworth K, Rangarajan A, Kattamuri C, Peterson RT, Eppig JJ, Thompson TB & & Matzuk MM 2013 Growth differentiation factor 9:bone morphogenetic protein 15 heterodimers are potent regulators of ovarian functions. Proceedings of the National Academy of Sciences of the United States of America 110 E776E785. (https://doi.org/10.1073/pnas.1218020110)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pennetier S, Uzbekova S, Perreau C, Papillier P, Mermillod P & & Dalbiès-Tran R 2004 Spatio-temporal expression of the germ cell marker genes MATER, ZAR1, GDF9, BMP15,andVASA in adult bovine tissues, oocytes, and preimplantation Embryos1. Biology of Reproduction 71 13591366. (https://doi.org/10.1095/biolreprod.104.030288)

    • Search Google Scholar
    • Export Citation
  • Quezada M, Wang J, Hoang V & & McGee EA 2012 Smad7 is a transforming growth factor-beta–inducible mediator of apoptosis in granulosa cells. Fertility and Sterility 97 14529.e1. (https://doi.org/10.1016/j.fertnstert.2012.03.024)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Reader KL, Haydon LJ, Littlejohn RP, Juengel JL & & McNatty KP 2012 Booroola BMPR1B mutation alters early follicular development and oocyte ultrastructure in sheep. Reproduction, Fertility, and Development 24 353361. (https://doi.org/10.1071/RD11095)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ruoss C, Tadros A, O'Shea T, McFarlane J & & Almahbobi G 2009 Ovarian follicle development in Booroola sheep exhibiting impaired bone morphogenetic protein signalling pathway. Reproduction 138 689696. (https://doi.org/10.1530/REP-09-0190)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Scaramuzzi RJ, Baird DT, Campbell BK, Driancourt MA, Dupont J, Fortune JE, Gilchrist RB, Martin GB, McNatty KP & McNeilly AS et al.2011 Regulation of folliculogenesis and the determination of ovulation rate in ruminants. Reproduction, Fertility, and Development 23 444467. (https://doi.org/10.1071/RD09161)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Shackell GH, Hudson NL, Heath DA, Lun S, Shaw L, Condell L, Blay LR & & McNatty KP 1993 Plasma gonadotropin concentrations and ovarian characteristics in Inverdale ewes that are heterozygous for a major gene (FecXI) on the X chromosome that influences ovulation rate. Biology of Reproduction 48 11501156. (https://doi.org/10.1095/biolreprod48.5.1150)

    • Search Google Scholar
    • Export Citation
  • Silva JRV, van den Hurk R, van Tol HT, Roelen BA & & Figueiredo JR 2005 Expression of growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15), and BMP receptors in the ovaries of goats. Molecular Reproduction and Development 70 1119. (https://doi.org/10.1002/mrd.20127)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Smith P, O WS, Hudson NL, Shaw L, Heath DA, Condell L, Phillips DJ & & McNatty KP 1993 Effects of the Booroola gene (FecB) on body-weight, ovarian development and hormone concentrations during fetal life. Journal of Reproduction and Fertility 98 4154. (https://doi.org/10.1530/jrf.0.0980041)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Souza CJH, McNeilly AS, Benavides MV, Melo EO & & Moraes JCF 2014 Mutation in the protease cleavage site of GDF9 increases ovulation rate and litter size in heterozygous ewes and causes infertility in homozygous ewes. Animal Genetics 45 732739. (https://doi.org/10.1111/age.12190)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Warren L, Murawski M, Wilk K, Zieba DA & & Bartlewski PM 2015 Suitability of antral follicle counts and computer-assisted analysis of ultrasonographic and magnetic resonance images for estimating follicular reserve in porcine, ovine and bovine ovaries ex situ. Experimental Biology and Medicine 240 576584. (https://doi.org/10.1177/1535370214560971)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Weiss A & & Attisano L 2013 The TGFbeta superfamily signaling pathway. Wiley Interdisciplinary Reviews. Developmental Biology 2 4763. (https://doi.org/10.1002/wdev.86)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wilson T, Wu XY, Juengel JL, Ross IK, Lumsden JM, Lord EA, Dodds KG, Walling GA, McEwan JC & O'Connell AR et al.2001 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. Biology of Reproduction 64 12251235. (https://doi.org/10.1095/biolreprod64.4.1225)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Xu SS, Gao L, Xie XL, Ren YL, Shen ZQ, Wang F, Shen M, Eyϸórsdóttir E, Hallsson JH & Kiseleva T et al.2018 Genome-wide association analyses highlight the potential for different genetic mechanisms for litter size among sheep breeds. Frontiers in Genetics 9 118. (https://doi.org/10.3389/fgene.2018.00118)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yan C, Wang P, DeMayo J, DeMayo FJ, Elvin JA, Carino C, Prasad SV, Skinner SS, Dunbar BS & Dube JL et al.2001 Synergistic roles of bone morphogenetic Protein 15 and growth differentiation factor 9 in ovarian function. Molecular Endocrinology 15 854866. (https://doi.org/10.1210/mend.15.6.0662)

    • PubMed
    • Search Google Scholar
    • Export Citation