Top

Journal of Ovarian Research

Published in:

Open Access 01-12-2013 | Brief communication

Bone morphogenetic proteins and the polycystic ovary syndrome

Authors: E Leonie AF van Houten, Joop SE Laven, Yvonne V Louwers, Anke McLuskey, Axel PN Themmen, Jenny A Visser

Published in: Journal of Ovarian Research | Issue 1/2013

Abstract

Background

Polycystic Ovary Syndrome (PCOS) is defined by two out of the following three criteria being met: oligo- or anovulation, hyperandrogenism, and polycystic ovaries. Affected women are often obese and insulin resistant. Although the etiology is still unknown, members of the Transforming Growth Factor β (TGFβ) family, including Bone Morphogenetic Proteins (BMPs) and anti-Müllerian hormone (AMH), have been implicated to play a role. In this pilot study we aimed to measure serum BMP levels in PCOS patients.

Methods

Twenty patients, fulfilling the definition of PCOS according to the Rotterdam Criteria, were randomly selected. Serum BMP2, -4, -6 and −7 levels were measured using commercially available BMP2, BMP4, BMP6 and BMP7 immunoassays.

Results

Serum BMP2, serum BMP4 and serum BMP6 levels were undetectable. Three patients had detectable serum BMP7 levels, albeit at the lower limit of the standard curve.

Conclusions

BMP levels were undetectable in almost all patients. This suggests that with the current sensitivity of the BMP assays, measurement of serum BMP levels is not suitable as a diagnostic tool for PCOS.

Franks S: Polycystic ovary syndrome. N Engl J Med 1995, 333: 853–861. 10.1056/NEJM199509283331307PubMedCrossRef

The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group: Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004, 19: 41–47.CrossRef

Escobar-Morreale HF, San Millan JL: Abdominal adiposity and the polycystic ovary syndrome. TEM 2007, 18: 266–272.PubMed

Franks S, Gharani N, Gilling-Smith C: Polycystic ovary syndrome: evidence for a primary disorder of ovarian steroidogenesis. J Steroid Biochem Mol Biol 1999, 69: 269–272. 10.1016/S0960-0760(99)00044-8PubMedCrossRef

Homburg R: Androgen circle of polycystic ovary syndrome. Hum Reprod 2009, 24: 1548–1555. 10.1093/humrep/dep049PubMedCrossRef

Blank SK, McCartney CR, Marshall JC: The origins and sequelae of abnormal neuroendocrine function in polycystic ovary syndrome. Hum Reprod Update 2006, 12: 351–361. 10.1093/humupd/dml017PubMedCrossRef

Franks S, Mason H, Willis D: Follicular dynamics in the polycystic ovary syndrome. Mol Cell Endocrinol 2000, 163: 49–52. 10.1016/S0303-7207(99)00239-7PubMedCrossRef

Erickson GF, Shimasaki S: The spatiotemporal expression pattern of the bone morphogenetic protein family in rat ovary cell types during the estrous cycle. Reprod Biol Endocrinol 2003, 1: 9. 10.1186/1477-7827-1-9PubMedCentralPubMedCrossRef

Knight PG, Glister C: TGF-beta superfamily members and ovarian follicle development. Reproduction (Cambridge, England) 2006, 132: 191–206. 10.1530/rep.1.01074CrossRef

10.

Shimasaki S, Moore RK, Otsuka F, Erickson GF: The bone morphogenetic protein system in mammalian reproduction. Endocr Rev 2004, 25: 72–101. 10.1210/er.2003-0007PubMedCrossRef

11.

Elvin JA, Yan C, Matzuk MM: Oocyte-expressed TGF-beta superfamily members in female fertility. Mol Cell Endocrinol 2000, 159: 1–5. 10.1016/S0303-7207(99)00185-9PubMedCrossRef

12.

Baarends WM, Uilenbroek JT, Kramer P, Hoogerbrugge JW, van Leeuwen EC, Themmen AP, Grootegoed JA: Anti-mullerian hormone and anti-mullerian hormone type II receptor messenger ribonucleic acid expression in rat ovaries during postnatal development, the estrous cycle, and gonadotropin-induced follicle growth. Endocrinology 1995, 136: 4951–4962. 10.1210/en.136.11.4951PubMed

13.

Fatehi AN, van den Hurk R, Colenbrander B, Daemen AJ, van Tol HT, Monteiro RM, Roelen BA, Bevers MM: Expression of bone morphogenetic protein2 (BMP2), BMP4 and BMP receptors in the bovine ovary but absence of effects of BMP2 and BMP4 during IVM on bovine oocyte nuclear maturation and subsequent embryo development. Theriogenology 2005, 63: 872–889. 10.1016/j.theriogenology.2004.05.013PubMedCrossRef

14.

Khalaf M, Morera J, Bourret A, Reznik Y, Denoual C, Herlicoviez M, Mittre H, Benhaim A: BMP system expression in GCs from polycystic ovary syndrome women and the in vitro effects of BMP4, BMP6, and BMP7 on GC steroidogenesis. Eur J Endocrinol 2013, 168: 437–444. 10.1530/EJE-12-0891PubMedCrossRef

15.

von Schalburg KR, McCarthy SP, Rise ML, Hutson JC, Davidson WS, Koop BF: Expression of morphogenic genes in mature ovarian and testicular tissues: potential stem-cell niche markers and patterning factors. Mol Reprod Dev 2006, 73: 142–152. 10.1002/mrd.20359PubMedCrossRef

16.

Visser JA, de Jong FH, Laven JS, Themmen AP: Anti-Mullerian hormone: a new marker for ovarian function. Reproduction (Cambridge, England) 2006, 131: 1–9. 10.1530/rep.1.00529CrossRef

17.

Cook CL, Siow Y, Brenner AG, Fallat ME: Relationship between serum mullerian-inhibiting substance and other reproductive hormones in untreated women with polycystic ovary syndrome and normal women. Fertil Steril 2002, 77: 141–146. 10.1016/S0015-0282(01)02944-2PubMedCrossRef

18.

Laven JS, Mulders AG, Visser JA, Themmen AP, De Jong FH, Fauser BC: Anti-Mullerian hormone serum concentrations in normoovulatory and anovulatory women of reproductive age. J Clin Endocrinol Metab 2004, 89: 318–323. 10.1210/jc.2003-030932PubMedCrossRef

19.

Pellatt L, Hanna L, Brincat M, Galea R, Brain H, Whitehead S, Mason H: Granulosa cell production of anti-Mullerian hormone is increased in polycystic ovaries. J Clin Endocrinol Metab 2007, 92: 240–245.PubMedCrossRef

20.

Imani B, Eijkemans MJ, te Velde ER, Habbema JD, Fauser BC: Predictors of patients remaining anovulatory during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. J Clin Endocrinol Metab 1998, 83: 2361–2365. 10.1210/jc.83.7.2361PubMed

21.

van Santbrink EJ, Hop WC, Fauser BC: Classification of normogonadotropic infertility: polycystic ovaries diagnosed by ultrasound versus endocrine characteristics of polycystic ovary syndrome. Fertil Steril 1997, 67: 452–458. 10.1016/S0015-0282(97)80068-4PubMedCrossRef

22.

Kevenaar ME, Laven JS, Fong SL, Uitterlinden AG, de Jong FH, Themmen AP, Visser JA: A functional anti-mullerian hormone gene polymorphism is associated with follicle number and androgen levels in polycystic ovary syndrome patients. J Clin Endocrinol Metab 2008, 93: 1310–1316. 10.1210/jc.2007-2205PubMedCrossRef

23.

Lie Fong S, Schipper I, de Jong FH, Themmen AP, Visser JA, Laven JS: Serum anti-Mullerian hormone and inhibin B concentrations are not useful predictors of ovarian response during ovulation induction treatment with recombinant follicle-stimulating hormone in women with polycystic ovary syndrome. Fertil Steril 2011, 96: 459–463. 10.1016/j.fertnstert.2011.05.084PubMedCrossRef

24.

Son JW, Kim MK, Park YM, Baek KH, Yoo SJ, Song KH, Son HS, Yoon KH, Lee WC, Cha BY: Association of serum bone morphogenetic protein 4 levels with obesity and metabolic syndrome in non-diabetic individuals. Endocr J 2011, 58: 39–46. 10.1507/endocrj.K10E-248PubMedCrossRef

25.

Giannoudis PV, Pountos I, Morley J, Perry S, Tarkin HI, Pape HC: Growth factor release following femoral nailing. Bone 2008, 42: 751–757. 10.1016/j.bone.2007.12.219PubMedCrossRef

26.

Gilchrist RB, Ritter LJ, Armstrong DT: Oocyte-somatic cell interactions during follicle development in mammals. Anim Reprod Sci 2004, 82–83: 431–446.PubMedCrossRef

27.

McNatty KP, Smith P, Moore LG, Reader K, Lun S, Hanrahan JP, Groome NP, Laitinen M, Ritvos O, Juengel JL: Oocyte-expressed genes affecting ovulation rate. Mol Cell Endocrinol 2005, 234: 57–66. 10.1016/j.mce.2004.08.013PubMedCrossRef

28.

Park MC, Park YB, Lee SK: Relationship of bone morphogenetic proteins to disease activity and radiographic damage in patients with ankylosing spondylitis. Scand J Rheumatol 2008, 37: 200–204. 10.1080/03009740701774941PubMedCrossRef

29.

Bozkaya YT, Aydin HH, Celik HA, Kayikcioglu M, Payzin S, Kultursay H, Aydin M, Yesil M, Can LH, Hasdemir C: Increased myocardial collagen turnover in patients with progressive cardiac conduction disease. Pacing Clin Electrophysiol 2008, 31: 1284–1290. 10.1111/j.1540-8159.2008.01179.xPubMedCrossRef

30.

Wendling D, Cedoz JP, Racadot E: Serum levels of MMP-3 and cathepsin K in patients with ankylosing spondylitis: effect of TNFalpha antagonist therapy. Joint Bone Spine 2008, 75: 559–562. 10.1016/j.jbspin.2008.01.026PubMedCrossRef

31.

Eldar-Geva T, Spitz IM, Groome NP, Margalioth EJ, Homburg R: Follistatin and activin A serum concentrations in obese and non-obese patients with polycystic ovary syndrome. Hum Reprod 2001, 16: 2552–2556. 10.1093/humrep/16.12.2552PubMedCrossRef

Title: Bone morphogenetic proteins and the polycystic ovary syndrome
Authors: E Leonie AF van Houten
Joop SE Laven
Yvonne V Louwers
Anke McLuskey
Axel PN Themmen
Jenny A Visser
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Journal of Ovarian Research / Issue 1/2013
Electronic ISSN: 1757-2215
DOI: https://doi.org/10.1186/1757-2215-6-32

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Bone morphogenetic proteins and the polycystic ovary syndrome

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2013

Massive edema of ovary with cytogenetic alteration of chromosome 12q13-15 in adolescent patient: a case report

mEH Tyr113His polymorphism and the risk of ovarian cancer development

Ovarian Sertoli–Leydig cell tumors: MRI findings and pathological correlation

Altered expression of miRNAs in a dihydrotestosterone-induced rat PCOS model

Value of 3.0 T diffusion-weighted imaging in discriminating thecoma and fibrothecoma from other adnexal solid masses

Mosaic pregnancy after transfer of a “euploid” blastocyst screened by DNA microarray