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Published in: Journal of Ovarian Research 1/2014

Open Access 01-12-2014 | Research

Anti Müllerian Hormone (AMH) level and expression in mural and cumulus cells in relation to age

Authors: Alon Kedem, Yuval Yung, Gil M Yerushalmi, Jigal Haas, Ettie Maman, Mirit Hanochi, Rina Hemi, Raoul Orvieto, Jehoshua Dor, Ariel Hourvitz

Published in: Journal of Ovarian Research | Issue 1/2014

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Abstract

Background

Serum AMH is declining with age and is highly associated with ovarian follicular reserve and disordered folliculogenesis. However, the precise role of AMH in the process of human follicular aging has still to be determined.

Aim

This study investigates AMH level in the follicular fluid (FF) and mRNA expression pattern in cumulus and mural granulosa cells of human ovarian follicles in relation to age.

Methods

We conducted a prospective study. Sixty-eight women undergoing In vitro fertilization (IVF) treatment were enrolled in the study. We obtained FF, mural and cumulus granulosa cells from large preovulatory follicles (17-20 mm) of 21–35 years old women (n = 40) and 40–45 years old women (n = 28) during oocyte pickup.

Results

Higher level of AMH mRNA expression in cumulus cells was observed in the older age group compared to the younger (P <0.01). In accordance with AMH mRNA expression results, FF AMH protein levels were significantly higher in the older group than in the younger group (4.7 ± 1.1 ng\ml and 2.3 ± 0.2 ng\ml respectively, p < 0.002).

Conclusions

AMH is highly expressed and secreted from cumulus GCs of advanced age patients. This remarkable correlation between AMH mRNA levels in cumulus cells in respect to age suggests that AMH may be involved in follicular aging process.
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Literature
1.
go back to reference Cate RL, Mattaliano RJ, Hession C, Tizard R, Farber NM, Cheung A, Ninfa EG, Frey AZ, Gash DJ, Chow EP: Isolation of the bovine and human genes for Mullerian inhibiting substance and expression of the human gene in animal cells. Cell 1986, 45: 685–698. 10.1016/0092-8674(86)90783-XCrossRefPubMed Cate RL, Mattaliano RJ, Hession C, Tizard R, Farber NM, Cheung A, Ninfa EG, Frey AZ, Gash DJ, Chow EP: Isolation of the bovine and human genes for Mullerian inhibiting substance and expression of the human gene in animal cells. Cell 1986, 45: 685–698. 10.1016/0092-8674(86)90783-XCrossRefPubMed
2.
go back to reference Knight PG, Glister C: Local roles of TGF-beta superfamily members in the control of ovarian follicle development. Anim Reprod Sci 2003, 78: 165–183. 10.1016/S0378-4320(03)00089-7CrossRefPubMed Knight PG, Glister C: Local roles of TGF-beta superfamily members in the control of ovarian follicle development. Anim Reprod Sci 2003, 78: 165–183. 10.1016/S0378-4320(03)00089-7CrossRefPubMed
3.
go back to reference Seifer DB, Maclaughlin DT: Mullerian inhibiting substance is an ovarian growth factor of emerging clinical significance. Fertil Steril 2007, 88: 539–546. 10.1016/j.fertnstert.2007.02.014CrossRefPubMed Seifer DB, Maclaughlin DT: Mullerian inhibiting substance is an ovarian growth factor of emerging clinical significance. Fertil Steril 2007, 88: 539–546. 10.1016/j.fertnstert.2007.02.014CrossRefPubMed
4.
go back to reference Vigier B, Picard JY, Tran D, Legeai L, Josso N: Production of anti-Mullerian hormone: another homology between Sertoli and granulosa cells. Endocrinology 1984, 114: 1315–1320. 10.1210/endo-114-4-1315CrossRefPubMed Vigier B, Picard JY, Tran D, Legeai L, Josso N: Production of anti-Mullerian hormone: another homology between Sertoli and granulosa cells. Endocrinology 1984, 114: 1315–1320. 10.1210/endo-114-4-1315CrossRefPubMed
5.
go back to reference Kedem A, Hourvitz A, Yung Y, Shalev L, Yerushalmi GM, Kanety H, Hanochi M, Maman E: Anti-Mullerian hormone (AMH) downregulation in late antral stages is impaired in PCOS patients. A study in normo-ovulatory and PCOS patients undergoing in vitro maturation (IVM) treatments. Gynecol Endocrinol 2013, 29: 651–656. 10.3109/09513590.2013.798279CrossRefPubMed Kedem A, Hourvitz A, Yung Y, Shalev L, Yerushalmi GM, Kanety H, Hanochi M, Maman E: Anti-Mullerian hormone (AMH) downregulation in late antral stages is impaired in PCOS patients. A study in normo-ovulatory and PCOS patients undergoing in vitro maturation (IVM) treatments. Gynecol Endocrinol 2013, 29: 651–656. 10.3109/09513590.2013.798279CrossRefPubMed
6.
go back to reference Andersen CY, Schmidt KT, Kristensen SG, Rosendahl M, Byskov AG, Ernst E: Concentrations of AMH and inhibin-B in relation to follicular diameter in normal human small antral follicles. Hum Reprod 2010, 25: 1282–1287. 10.1093/humrep/deq019CrossRefPubMed Andersen CY, Schmidt KT, Kristensen SG, Rosendahl M, Byskov AG, Ernst E: Concentrations of AMH and inhibin-B in relation to follicular diameter in normal human small antral follicles. Hum Reprod 2010, 25: 1282–1287. 10.1093/humrep/deq019CrossRefPubMed
7.
go back to reference Durlinger AL, Gruijters MJ, Kramer P, Karels B, Ingraham HA, Nachtigal MW, Uilenbroek JT, Grootegoed JA, Themmen AP: Anti-Mullerian hormone inhibits initiation of primordial follicle growth in the mouse ovary. Endocrinology 2002, 143: 1076–1084.PubMed Durlinger AL, Gruijters MJ, Kramer P, Karels B, Ingraham HA, Nachtigal MW, Uilenbroek JT, Grootegoed JA, Themmen AP: Anti-Mullerian hormone inhibits initiation of primordial follicle growth in the mouse ovary. Endocrinology 2002, 143: 1076–1084.PubMed
8.
go back to reference Fanchin R, Louafi N, Mendez Lozano DH, Frydman N, Frydman R, Taieb J: Per-follicle measurements indicate that anti-mullerian hormone secretion is modulated by the extent of follicular development and luteinization and may reflect qualitatively the ovarian follicular status. Fertil Steril 2005, 84: 167–173. 10.1016/j.fertnstert.2005.01.115CrossRefPubMed Fanchin R, Louafi N, Mendez Lozano DH, Frydman N, Frydman R, Taieb J: Per-follicle measurements indicate that anti-mullerian hormone secretion is modulated by the extent of follicular development and luteinization and may reflect qualitatively the ovarian follicular status. Fertil Steril 2005, 84: 167–173. 10.1016/j.fertnstert.2005.01.115CrossRefPubMed
9.
go back to reference Weenen C, Laven JS, Von Bergh AR, Cranfield M, Groome NP, Visser JA, Kramer P, Fauser BC, Themmen AP: Anti-Mullerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod 2004, 10: 77–83. 10.1093/molehr/gah015CrossRefPubMed Weenen C, Laven JS, Von Bergh AR, Cranfield M, Groome NP, Visser JA, Kramer P, Fauser BC, Themmen AP: Anti-Mullerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod 2004, 10: 77–83. 10.1093/molehr/gah015CrossRefPubMed
10.
go back to reference Faddy MJ, Gosden RG, Gougeon A, Richardson SJ, Nelson JF: Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. Hum Reprod 1992, 7: 1342–1346.PubMed Faddy MJ, Gosden RG, Gougeon A, Richardson SJ, Nelson JF: Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. Hum Reprod 1992, 7: 1342–1346.PubMed
11.
go back to reference Tilly JL: Emerging technologies to control oocyte apoptosis are finally treading on fertile ground. TheScientificWorldJournal 2001, 1: 181–183. 10.1100/tsw.2001.39CrossRefPubMed Tilly JL: Emerging technologies to control oocyte apoptosis are finally treading on fertile ground. TheScientificWorldJournal 2001, 1: 181–183. 10.1100/tsw.2001.39CrossRefPubMed
12.
go back to reference Kedem-Dickman A, Maman E, Yung Y, Yerushalmi GM, Hemi R, Hanochi M, Dor J, Hourvitz A: Anti-Mullerian hormone is highly expressed and secreted from cumulus granulosa cells of stimulated preovulatory immature and atretic oocytes. Reprod Biomed Online 2012, 24: 540–546. 10.1016/j.rbmo.2012.01.023CrossRefPubMed Kedem-Dickman A, Maman E, Yung Y, Yerushalmi GM, Hemi R, Hanochi M, Dor J, Hourvitz A: Anti-Mullerian hormone is highly expressed and secreted from cumulus granulosa cells of stimulated preovulatory immature and atretic oocytes. Reprod Biomed Online 2012, 24: 540–546. 10.1016/j.rbmo.2012.01.023CrossRefPubMed
13.
go back to reference Maman E, Yung Y, Cohen B, Konopnicki S, Dal Canto M, Fadini R, Kanety H, Kedem A, Dor J, Hourvitz A: Expression and regulation of sFRP family members in human granulosa cells. Mol Hum Reprod 2011, 17: 399–404. 10.1093/molehr/gar010CrossRefPubMed Maman E, Yung Y, Cohen B, Konopnicki S, Dal Canto M, Fadini R, Kanety H, Kedem A, Dor J, Hourvitz A: Expression and regulation of sFRP family members in human granulosa cells. Mol Hum Reprod 2011, 17: 399–404. 10.1093/molehr/gar010CrossRefPubMed
14.
go back to reference Kedem A, Haas J, Geva LL, Yerushalmi G, Gilboa Y, Kanety H, Hanochi M, Maman E, Hourvitz A: Ongoing pregnancy rates in women with low and extremely low AMH levels. A multivariate analysis of 769 cycles. PLoS One 2013, 8: e81629. 10.1371/journal.pone.0081629PubMedCentralCrossRefPubMed Kedem A, Haas J, Geva LL, Yerushalmi G, Gilboa Y, Kanety H, Hanochi M, Maman E, Hourvitz A: Ongoing pregnancy rates in women with low and extremely low AMH levels. A multivariate analysis of 769 cycles. PLoS One 2013, 8: e81629. 10.1371/journal.pone.0081629PubMedCentralCrossRefPubMed
15.
go back to reference La Marca A, Giulini S, Tirelli A, Bertucci E, Marsella T, Xella S, Volpe A: Anti-Mullerian hormone measurement on any day of the menstrual cycle strongly predicts ovarian response in assisted reproductive technology. Hum Reprod 2007, 22: 766–771. 10.1093/humrep/del421CrossRefPubMed La Marca A, Giulini S, Tirelli A, Bertucci E, Marsella T, Xella S, Volpe A: Anti-Mullerian hormone measurement on any day of the menstrual cycle strongly predicts ovarian response in assisted reproductive technology. Hum Reprod 2007, 22: 766–771. 10.1093/humrep/del421CrossRefPubMed
16.
go back to reference Nelson SM, Anderson RA, Broekmans FJ, Raine-Fenning N, Fleming R, La Marca A: Anti-Mullerian hormone: clairvoyance or crystal clear? Hum Reprod 2012, 27: 631–636. 10.1093/humrep/der446CrossRefPubMed Nelson SM, Anderson RA, Broekmans FJ, Raine-Fenning N, Fleming R, La Marca A: Anti-Mullerian hormone: clairvoyance or crystal clear? Hum Reprod 2012, 27: 631–636. 10.1093/humrep/der446CrossRefPubMed
17.
go back to reference Jeppesen JV, Anderson RA, Kelsey TW, Christiansen SL, Kristensen SG, Jayaprakasan K, Raine-Fenning N, Campbell BK, Yding Andersen C: Which follicles make the most anti-Mullerian hormone in humans? Evidence for an abrupt decline in AMH production at the time of follicle selection. Mol Hum Reprod 2013, 19: 519–527. 10.1093/molehr/gat024CrossRefPubMed Jeppesen JV, Anderson RA, Kelsey TW, Christiansen SL, Kristensen SG, Jayaprakasan K, Raine-Fenning N, Campbell BK, Yding Andersen C: Which follicles make the most anti-Mullerian hormone in humans? Evidence for an abrupt decline in AMH production at the time of follicle selection. Mol Hum Reprod 2013, 19: 519–527. 10.1093/molehr/gat024CrossRefPubMed
18.
go back to reference di Clemente N, Wilson C, Faure E, Boussin L, Carmillo P, Tizard R, Picard JY, Vigier B, Josso N, Cate R: Cloning, expression, and alternative splicing of the receptor for anti-Mullerian hormone. Mol Endocrinol 1994, 8: 1006–1020.PubMed di Clemente N, Wilson C, Faure E, Boussin L, Carmillo P, Tizard R, Picard JY, Vigier B, Josso N, Cate R: Cloning, expression, and alternative splicing of the receptor for anti-Mullerian hormone. Mol Endocrinol 1994, 8: 1006–1020.PubMed
19.
go back to reference Pellatt L, Rice S, Dilaver N, Heshri A, Galea R, Brincat M, Brown K, Simpson ER, Mason HD: Anti-Mullerian hormone reduces follicle sensitivity to follicle-stimulating hormone in human granulosa cells. Fertil Steril 2011, 96: 1246–1251. e1241 10.1016/j.fertnstert.2011.08.015CrossRefPubMed Pellatt L, Rice S, Dilaver N, Heshri A, Galea R, Brincat M, Brown K, Simpson ER, Mason HD: Anti-Mullerian hormone reduces follicle sensitivity to follicle-stimulating hormone in human granulosa cells. Fertil Steril 2011, 96: 1246–1251. e1241 10.1016/j.fertnstert.2011.08.015CrossRefPubMed
20.
go back to reference Mehta BN, Chimote MN, Chimote NN, Nath NM, Chimote NM: Follicular-fluid anti-Mullerian hormone (FF AMH) is a plausible biochemical indicator of functional viability of oocyte in conventional in vitro fertilization (IVF) cycles. J Hum Reprod Sci 2013, 6: 99–105. 10.4103/0974-1208.117168PubMedCentralCrossRefPubMed Mehta BN, Chimote MN, Chimote NN, Nath NM, Chimote NM: Follicular-fluid anti-Mullerian hormone (FF AMH) is a plausible biochemical indicator of functional viability of oocyte in conventional in vitro fertilization (IVF) cycles. J Hum Reprod Sci 2013, 6: 99–105. 10.4103/0974-1208.117168PubMedCentralCrossRefPubMed
21.
go back to reference Fanchin R, Mendez Lozano DH, Frydman N, Gougeon A, di Clemente N, Frydman R, Taieb J: Anti-Mullerian hormone concentrations in the follicular fluid of the preovulatory follicle are predictive of the implantation potential of the ensuing embryo obtained by in vitro fertilization. J Clin Endocrinol Metab 2007, 92: 1796–1802. 10.1210/jc.2006-1053CrossRefPubMed Fanchin R, Mendez Lozano DH, Frydman N, Gougeon A, di Clemente N, Frydman R, Taieb J: Anti-Mullerian hormone concentrations in the follicular fluid of the preovulatory follicle are predictive of the implantation potential of the ensuing embryo obtained by in vitro fertilization. J Clin Endocrinol Metab 2007, 92: 1796–1802. 10.1210/jc.2006-1053CrossRefPubMed
Metadata
Title
Anti Müllerian Hormone (AMH) level and expression in mural and cumulus cells in relation to age
Authors
Alon Kedem
Yuval Yung
Gil M Yerushalmi
Jigal Haas
Ettie Maman
Mirit Hanochi
Rina Hemi
Raoul Orvieto
Jehoshua Dor
Ariel Hourvitz
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2014
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-014-0113-3

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