Ablation of TGFBR3 (betaglycan) in oocytes does not affect fertility in female mice

in Reproduction
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  • 1 Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada
  • 2 Department of Obstetrics and Gynecology, McGill University, Montréal, Québec, Canada

Correspondence should be addressed to D J Bernard; Email: daniel.bernard@mcgill.ca
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Ovarian follicle development is regulated by locally produced TGFβ superfamily members. The TGFβ type III receptor (TGFBR3, or betaglycan), which regulates the actions of diverse TGFβ ligands, including inhibins, is expressed in different ovarian cell types. However, its functional roles in the ovary have not been investigated in vivo. Here, we ablated Tgfbr3 in murine oocytes using the Cre-loxP system. Oocyte-specific Tgfbr3 knockout (cKO) females were fertile, producing litters of similar size and frequency as controls. Their ovarian weights and histology were also normal. Though we confirmed efficient recombination of the floxed alleles, we did not detect Tgfbr3 mRNA in purified oocytes from superovulated cKO or control mice. These results challenge earlier observations of betaglycan protein expression in this cell type. Regardless, Tgfbr3 in the murine oocyte is clearly dispensable for female fertility.

 

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  • Attisano L & Wrana JL 2002 Signal transduction by the TGF-beta superfamily. Science 296 1646164 7. (https://doi.org/10.1126/science.1071809)

    • Search Google Scholar
    • Export Citation
  • Bilandzic M & Stenvers KL 2011 Betaglycan: a multifunctional accessory. Molecular and Cellular Endocrinology 339 18018 9. (https://doi.org/10.1016/j.mce.2011.04.014)

    • Search Google Scholar
    • Export Citation
  • Caligioni CS 2009 Assessing reproductive status/stages in mice. Current Protocols in Neuroscience Appendix 4 Appendix 4I. (https://doi.org/10.1002/0471142301.nsa04is48)

    • Search Google Scholar
    • Export Citation
  • Chapman SC, Bernard DJ, Jelen J & Woodruff TK 2002 Properties of inhibin binding to betaglycan, InhBP/p120 and the activin type II receptors. Molecular and Cellular Endocrinology 196 7993. (https://doi.org/10.1016/s0303-7207(0200227-7)

    • 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 5315 35. (https://doi.org/10.1038/383531a0)

    • Search Google Scholar
    • Export Citation
  • Drummond AE, Le MT, Ethier JF, Dyson M & Findlay JK 2002 Expression and localization of activin receptors, Smads, and beta glycan to the postnatal rat ovary. Endocrinology 143 142314 33. (https://doi.org/10.1210/endo.143.4.8728)

    • Search Google Scholar
    • Export Citation
  • Farnworth PG, Stanton PG, Wang Y, Escalona R, Findlay JK & Ooi GT 2006 Inhibins differentially antagonize activin and bone morphogenetic protein action in a mouse adrenocortical cell line. Endocrinology 147 346234 71. (https://doi.org/10.1210/en.2006-0023)

    • Search Google Scholar
    • Export Citation
  • Gilchrist RB, Ritter LJ & Armstrong DT 2004 Oocyte-somatic cell interactions during follicle development in mammals. Animal Reproduction Science 82–83 431446. (https://doi.org/10.1016/j.anireprosci.2004.05.017)

    • Search Google Scholar
    • Export Citation
  • Glister C, Satchell L & Knight PG 2010 Changes in expression of bone morphogenetic proteins (BMPs), their receptors and inhibin co-receptor betaglycan during bovine antral follicle development: inhibin can antagonize the suppressive effect of BMPs on thecal androgen production. Reproduction 140 699712. (https://doi.org/10.1530/REP-10-0216)

    • Search Google Scholar
    • Export Citation
  • Hillier SG, Yong EL, Illingworth PJ, Baird DT, Schwall RH & Mason AJ 1991 Effect of recombinant activin on androgen synthesis in cultured human thecal cells. Journal of Clinical Endocrinology and Metabolism 72 12061 21 1. (https://doi.org/10.1210/jcem-72-6-1206)

    • Search Google Scholar
    • Export Citation
  • Juengel JL & McNatty KP 2005 The role of proteins of the transforming growth factor-beta superfamily in the intraovarian regulation of follicular development. Human Reproduction Update 11 1431 60. (https://doi.org/10.1093/humupd/dmh061)

    • Search Google Scholar
    • Export Citation
  • Kidder GM & Vanderhyden BC 2010 Bidirectional communication between oocytes and follicle cells: ensuring oocyte developmental competence. Canadian Journal of Physiology and Pharmacology 88 399413. (https://doi.org/10.1139/y10-009)

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

    • Search Google Scholar
    • Export Citation
  • Knight PG, Satchell L & Glister C 2012 Intra-ovarian roles of activins and inhibins. Molecular and Cellular Endocrinology 359 5365. (https://doi.org/10.1016/j.mce.2011.04.024)

    • Search Google Scholar
    • Export Citation
  • Lan ZJ, Xu X & Cooney AJ 2004 Differential oocyte-specific expression of Cre recombinase activity in GDF-9-iCre, Zp3cre, and Msx2Cre transgenic mice. Biology of Reproduction 71 146914 74. (https://doi.org/10.1095/biolreprod.104.031757)

    • Search Google Scholar
    • Export Citation
  • Lewis KA, Gray PC, Blount AL, Macconell LA, Wiater E, Bilezikjian LM & Vale W 2000 Betaglycan binds inhibin and can mediate functional antagonism of activin signalling. Nature 404 411–414. (https://doi.org/10.1038/35006129)

    • Search Google Scholar
    • Export Citation
  • Li X, Tripurani SK, James R & Pangas SA 2012 Minimal fertility defects in mice deficient in oocyte-expressed Smad4. Biology of Reproduction 86 16. (https://doi.org/10.1095/biolreprod.111.094375)

    • Search Google Scholar
    • Export Citation
  • Li Y, Schang G, Boehm U, Deng CX, Graff J & Bernard DJ 2017 SMAD3 regulates follicle-stimulating hormone synthesis by pituitary gonadotrope cells in vivo. Journal of Biological Chemistry 292 23012314. (https://doi.org/10.1074/jbc.M116.759167)

    • Search Google Scholar
    • Export Citation
  • Li Y, Fortin J, Ongaro L, Zhou X, Boehm U, Schneyer A, Bernard DJ & Lin HY 2018 Betaglycan (TGFBR3) functions as an inhibin A, but not inhibin B, coreceptor in pituitary gonadotrope cells in mice. Endocrinology 159 40774091. (https://doi.org/10.1210/en.2018-00770)

    • Search Google Scholar
    • Export Citation
  • Ling N, Ying SY, Ueno N, Shimasaki S, Esch F, Hotta M & Guillemin R 1986a A homodimer of the beta-subunits of inhibin A stimulates the secretion of pituitary follicle stimulating hormone. Biochemical and Biophysical Research Communications 138 112911 37. (https://doi.org/10.1016/s0006-291x(8680400-4)

    • Search Google Scholar
    • Export Citation
  • Ling N, Ying SY, Ueno N, Shimasaki S, Esch F, Hotta M & Guillemin R 1986b Pituitary FSH is released by a heterodimer of the beta-subunits from the two forms of inhibin. Nature 321 7797 82. (https://doi.org/10.1038/321779a0)

    • Search Google Scholar
    • Export Citation
  • Macconell LA, Leal AM & Vale WW 2002 The distribution of betaglycan protein and mRNA in rat brain, pituitary, and gonads: implications for a role for betaglycan in inhibin-mediated reproductive functions. Endocrinology 143 106610 75. (https://doi.org/10.1210/endo.143.3.8707)

    • Search Google Scholar
    • Export Citation
  • Massague J 1998 TGF-beta signal transduction. Annual Review of Biochemistry 67 7537 91. (https://doi.org/10.1146/annurev.biochem.67.1.753)

    • Search Google Scholar
    • Export Citation
  • Matzuk MM, Burns KH, Viveiros MM & Eppig JJ 2002 Intercellular communication in the mammalian ovary: oocytes carry the conversation. Science 296 217821 80. (https://doi.org/10.1126/science.1071965)

    • Search Google Scholar
    • Export Citation
  • Myers M & Pangas SA 2010 Regulatory roles of transforming growth factor beta family members in folliculogenesis. Wiley Interdisciplinary Reviews: Systems Biology and Medicine 2 117125. (https://doi.org/10.1002/wsbm.21)

    • Search Google Scholar
    • Export Citation
  • O WS, Robertson DM & de Kretser DM 1989 Inhibin as an oocyte meiotic inhibitor. Molecular and Cellular Endocrinology 62 3073 11. (https://doi.org/10.1016/0303-7207(8990018-x)

    • Search Google Scholar
    • Export Citation
  • Pangas SA, Li X, Robertson EJ & Matzuk MM 2006 Premature luteinization and cumulus cell defects in ovarian-specific Smad4 knockout mice. Molecular Endocrinology 20 140614 22. (https://doi.org/10.1210/me.2005-0462)

    • Search Google Scholar
    • Export Citation
  • Sadatsuki M, Tsutsumi O, Yamada R, Muramatsu M & Taketani Y 1993 Local regulatory effects of activin A and follistatin on meiotic maturation of rat oocytes. Biochemical and Biophysical Research Communications 196 3883 95. (https://doi.org/10.1006/bbrc.1993.2261)

    • Search Google Scholar
    • Export Citation
  • Sarraj MA, Chua HK, Umbers A, Loveland KL, Findlay JK & Stenvers KL 2007 Differential expression of TGFBR3 (betaglycan) in mouse ovary and testis during gonadogenesis. Growth Factors 25 3343 45. (https://doi.org/10.1080/08977190701833619)

    • Search Google Scholar
    • Export Citation
  • Silva CC & Knight PG 1998 Modulatory actions of activin-A and follistatin on the developmental competence of in vitro-matured bovine oocytes. Biology of Reproduction 58 5585 65. (https://doi.org/10.1095/biolreprod58.2.558)

    • Search Google Scholar
    • Export Citation
  • Silva CC, Groome NP & Knight PG 1999 Demonstration of a suppressive effect of inhibin alpha-subunit on the developmental competence of in vitro matured bovine oocytes. Journal of Reproduction and Fertility 115 38138 8. (https://doi.org/10.1530/jrf.0.1150381)

    • Search Google Scholar
    • Export Citation
  • Vale W, Wiater E, Gray P, Harrison C, Bilezikjian L & Choe S 2004 Activins and inhibins and their signaling. Annals of the New York Academy of Sciences 1038 14214 7. (https://doi.org/10.1196/annals.1315.023)

    • Search Google Scholar
    • Export Citation
  • Watson LN, Mottershead DG, Dunning KR, Robker RL, Gilchrist RB & Russell DL 2012 Heparan sulfate proteoglycans regulate responses to oocyte paracrine signals in ovarian follicle morphogenesis. Endocrinology 153 454445 55. (https://doi.org/10.1210/en.2012-1181)

    • Search Google Scholar
    • Export Citation
  • Wiater E & Vale W 2003 Inhibin is an antagonist of bone morphogenetic protein signaling. Journal of Biological Chemistry 278 793479 41. (https://doi.org/10.1074/jbc.M209710200)

    • Search Google Scholar
    • Export Citation
  • Wiater E, Lewis KA, Donaldson C, Vaughan J, Bilezikjian L & Vale W 2009 Endogenous betaglycan is essential for high-potency inhibin antagonism in gonadotropes. Molecular Endocrinology 23 103310 42. (https://doi.org/10.1210/me.2009-0021)

    • Search Google Scholar
    • Export Citation