Overexpression of anti-mullerian hormone disrupts gonadal sex differentiation, blocks sex hormone synthesis, and supports cell autonomous sex development in the chicken

Luke S. Lambeth, Kirsten Morris, Katie L. Ayers, Terry G. Wise, Terri O'Neil, Susanne Wilson, Yu Cao, Andrew H. Sinclair, Andrew D. Cutting, Timothy J. Doran, Craig A. Smith

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11 Citations (Scopus)

Abstract

The primary role of Anti-Müllerian hormone (AMH) during mammalian development is the regression of Müllerian ducts in males. This highly conserved function is retained in birds and is supported by the high levels of AMH expression in developing testes. Mammalian AMH expression is regulated by a combination of transcription factors, the most important being Sry-type high-mobility-group box transcription factor-9 (SOX9). In the chicken embryo, however, AMH mRNA expression precedes that of SOX9, leading to the view that AMH may play a more central role in avian testicular development. To define its role in chicken gonadal development, AMH was overexpressed using the RCASBP viral vector. AMH caused the gonads of both sexes to develop as small and undeveloped structures at both embryonic and adult stages. Molecular analysis revealed that although female gonads developed testis-like cords, gonads lacked Sertoli cells and were incapable of steroidogenesis. A similar gonadal phenotype was also observed in males, with a complete loss of both Sertoli cells, disrupted SOX9 expression and gonadal steroidogenesis. At sexual maturity both sexes showed a female external phenotype but retained sexually dimorphic body weights that matched their genetic sexes. These data suggest that AMH does not operate as an early testis activator in the chicken but can affect downstream events, such as sex steroid hormone production. In addition, this study provides a unique opportunity to assess chicken sexual development in an environment of sex hormone deficiency, demonstrating the importance of both hormonal signaling and direct cell autonomous factors for somatic sex identity in birds.
Original languageEnglish
Pages (from-to)1258-1275
Number of pages18
JournalEndocrinology
Volume157
Issue number3
DOIs
Publication statusPublished - Mar 2016

Cite this

Lambeth, Luke S. ; Morris, Kirsten ; Ayers, Katie L. ; Wise, Terry G. ; O'Neil, Terri ; Wilson, Susanne ; Cao, Yu ; Sinclair, Andrew H. ; Cutting, Andrew D. ; Doran, Timothy J. ; Smith, Craig A. / Overexpression of anti-mullerian hormone disrupts gonadal sex differentiation, blocks sex hormone synthesis, and supports cell autonomous sex development in the chicken. In: Endocrinology. 2016 ; Vol. 157, No. 3. pp. 1258-1275.
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title = "Overexpression of anti-mullerian hormone disrupts gonadal sex differentiation, blocks sex hormone synthesis, and supports cell autonomous sex development in the chicken",
abstract = "The primary role of Anti-M{\"u}llerian hormone (AMH) during mammalian development is the regression of M{\"u}llerian ducts in males. This highly conserved function is retained in birds and is supported by the high levels of AMH expression in developing testes. Mammalian AMH expression is regulated by a combination of transcription factors, the most important being Sry-type high-mobility-group box transcription factor-9 (SOX9). In the chicken embryo, however, AMH mRNA expression precedes that of SOX9, leading to the view that AMH may play a more central role in avian testicular development. To define its role in chicken gonadal development, AMH was overexpressed using the RCASBP viral vector. AMH caused the gonads of both sexes to develop as small and undeveloped structures at both embryonic and adult stages. Molecular analysis revealed that although female gonads developed testis-like cords, gonads lacked Sertoli cells and were incapable of steroidogenesis. A similar gonadal phenotype was also observed in males, with a complete loss of both Sertoli cells, disrupted SOX9 expression and gonadal steroidogenesis. At sexual maturity both sexes showed a female external phenotype but retained sexually dimorphic body weights that matched their genetic sexes. These data suggest that AMH does not operate as an early testis activator in the chicken but can affect downstream events, such as sex steroid hormone production. In addition, this study provides a unique opportunity to assess chicken sexual development in an environment of sex hormone deficiency, demonstrating the importance of both hormonal signaling and direct cell autonomous factors for somatic sex identity in birds.",
author = "Lambeth, {Luke S.} and Kirsten Morris and Ayers, {Katie L.} and Wise, {Terry G.} and Terri O'Neil and Susanne Wilson and Yu Cao and Sinclair, {Andrew H.} and Cutting, {Andrew D.} and Doran, {Timothy J.} and Smith, {Craig A.}",
year = "2016",
month = "3",
doi = "10.1210/en.2015-1571",
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Lambeth, LS, Morris, K, Ayers, KL, Wise, TG, O'Neil, T, Wilson, S, Cao, Y, Sinclair, AH, Cutting, AD, Doran, TJ & Smith, CA 2016, 'Overexpression of anti-mullerian hormone disrupts gonadal sex differentiation, blocks sex hormone synthesis, and supports cell autonomous sex development in the chicken', Endocrinology, vol. 157, no. 3, pp. 1258-1275. https://doi.org/10.1210/en.2015-1571

Overexpression of anti-mullerian hormone disrupts gonadal sex differentiation, blocks sex hormone synthesis, and supports cell autonomous sex development in the chicken. / Lambeth, Luke S.; Morris, Kirsten; Ayers, Katie L.; Wise, Terry G.; O'Neil, Terri; Wilson, Susanne; Cao, Yu; Sinclair, Andrew H.; Cutting, Andrew D.; Doran, Timothy J.; Smith, Craig A.

In: Endocrinology, Vol. 157, No. 3, 03.2016, p. 1258-1275.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Overexpression of anti-mullerian hormone disrupts gonadal sex differentiation, blocks sex hormone synthesis, and supports cell autonomous sex development in the chicken

AU - Lambeth, Luke S.

AU - Morris, Kirsten

AU - Ayers, Katie L.

AU - Wise, Terry G.

AU - O'Neil, Terri

AU - Wilson, Susanne

AU - Cao, Yu

AU - Sinclair, Andrew H.

AU - Cutting, Andrew D.

AU - Doran, Timothy J.

AU - Smith, Craig A.

PY - 2016/3

Y1 - 2016/3

N2 - The primary role of Anti-Müllerian hormone (AMH) during mammalian development is the regression of Müllerian ducts in males. This highly conserved function is retained in birds and is supported by the high levels of AMH expression in developing testes. Mammalian AMH expression is regulated by a combination of transcription factors, the most important being Sry-type high-mobility-group box transcription factor-9 (SOX9). In the chicken embryo, however, AMH mRNA expression precedes that of SOX9, leading to the view that AMH may play a more central role in avian testicular development. To define its role in chicken gonadal development, AMH was overexpressed using the RCASBP viral vector. AMH caused the gonads of both sexes to develop as small and undeveloped structures at both embryonic and adult stages. Molecular analysis revealed that although female gonads developed testis-like cords, gonads lacked Sertoli cells and were incapable of steroidogenesis. A similar gonadal phenotype was also observed in males, with a complete loss of both Sertoli cells, disrupted SOX9 expression and gonadal steroidogenesis. At sexual maturity both sexes showed a female external phenotype but retained sexually dimorphic body weights that matched their genetic sexes. These data suggest that AMH does not operate as an early testis activator in the chicken but can affect downstream events, such as sex steroid hormone production. In addition, this study provides a unique opportunity to assess chicken sexual development in an environment of sex hormone deficiency, demonstrating the importance of both hormonal signaling and direct cell autonomous factors for somatic sex identity in birds.

AB - The primary role of Anti-Müllerian hormone (AMH) during mammalian development is the regression of Müllerian ducts in males. This highly conserved function is retained in birds and is supported by the high levels of AMH expression in developing testes. Mammalian AMH expression is regulated by a combination of transcription factors, the most important being Sry-type high-mobility-group box transcription factor-9 (SOX9). In the chicken embryo, however, AMH mRNA expression precedes that of SOX9, leading to the view that AMH may play a more central role in avian testicular development. To define its role in chicken gonadal development, AMH was overexpressed using the RCASBP viral vector. AMH caused the gonads of both sexes to develop as small and undeveloped structures at both embryonic and adult stages. Molecular analysis revealed that although female gonads developed testis-like cords, gonads lacked Sertoli cells and were incapable of steroidogenesis. A similar gonadal phenotype was also observed in males, with a complete loss of both Sertoli cells, disrupted SOX9 expression and gonadal steroidogenesis. At sexual maturity both sexes showed a female external phenotype but retained sexually dimorphic body weights that matched their genetic sexes. These data suggest that AMH does not operate as an early testis activator in the chicken but can affect downstream events, such as sex steroid hormone production. In addition, this study provides a unique opportunity to assess chicken sexual development in an environment of sex hormone deficiency, demonstrating the importance of both hormonal signaling and direct cell autonomous factors for somatic sex identity in birds.

UR - http://www.ncbi.nlm.nih.gov/pubmed/26809122

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DO - 10.1210/en.2015-1571

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