Expression of the Insulin-like Growth Factor System in First- and Second-Trimester Human Embryonic and Fetal Gonads

Linn Salto Mamsen; Zafeiri Aikaterini; Jane Alrø Bøtkjær; Jonna Rasmussen Hardlei; Erik Ernst; Claus Oxvig; Paul A Fowler; Claus Yding Andersen

doi:10.1210/clinem/dgaa470

Expression of the Insulin-like Growth Factor System in First- and Second-Trimester Human Embryonic and Fetal Gonads

Linn Salto Mamsen, Zafeiri Aikaterini, Jane Alrø Bøtkjær, Jonna Rasmussen Hardlei, Erik Ernst, Claus Oxvig, Paul A Fowler, Claus Yding Andersen

Abstract

CONTEXT: Insulin-like growth factor (IGF) signaling is crucial for sex differentiation and development of Leydig and Sertoli cells in fetal mice testes. No such information is available for human embryonic and fetal testes and ovaries.

OBJECTIVE: To investigate presence and activity of the IGF signaling system during human embryonic and fetal ovarian and testicular development.

DESIGN: Human embryonic and fetal gonads were obtained following legal terminations of pregnancies. Gene expression was assessed by microarray and qPCR transcript analyses. Proteins of the IGF system components were detected with immunohistochemistry and immunofluorescence analyses. Specimens were included from 2010 to 2017.

SETTING: University Hospital.

PATIENTS/PARTICIPANTS: Ovaries and testes from a total of 124 human embryos and fetuses aged 5 to 17 postconception weeks were obtained from healthy women aged 16 to 47 years resident in Denmark or Scotland.

MAIN OUTCOME MEASURES: Gene expression analysis using microarray was performed in 46 specimens and qPCR analysis in 56 specimens, both sexes included. Protein analysis included 22 specimens (11 ovaries, 11 testes).

RESULTS: IGF system members were detected in embryonic and fetal testes and ovaries, both at gene transcript and protein level. A higher expression of IGF regulators was detected in testes than ovaries, with a preferred localization to Leydig cells.

CONCLUSIONS: These data indicate that the IGF system is active during very early gestation, when it may have a regulatory role in Leydig cells.

Original language	English
Journal	The Journal of clinical endocrinology and metabolism
Volume	105
Issue number	9
Pages (from-to)	E3157-E3168
ISSN	0021-972X
DOIs	https://doi.org/10.1210/clinem/dgaa470
Publication status	Published - 1 Sept 2020

Keywords

human gonadal development
IGF signaling
stanniocalcins
PAPP-A
first- and second-trimester gonads

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10.1210/clinem/dgaa470

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Expression of the Insulin-like Growth Factor System in First- and Second-Trimester Human Embryonic and Fetal Gonads. / Mamsen, Linn Salto; Aikaterini, Zafeiri; Bøtkjær, Jane Alrø et al.
In: The Journal of clinical endocrinology and metabolism, Vol. 105, No. 9, 01.09.2020, p. E3157-E3168.

Research output: Contribution to journal › Journal article › Research › peer-review

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title = "Expression of the Insulin-like Growth Factor System in First- and Second-Trimester Human Embryonic and Fetal Gonads",

abstract = "CONTEXT: Insulin-like growth factor (IGF) signaling is crucial for sex differentiation and development of Leydig and Sertoli cells in fetal mice testes. No such information is available for human embryonic and fetal testes and ovaries.OBJECTIVE: To investigate presence and activity of the IGF signaling system during human embryonic and fetal ovarian and testicular development.DESIGN: Human embryonic and fetal gonads were obtained following legal terminations of pregnancies. Gene expression was assessed by microarray and qPCR transcript analyses. Proteins of the IGF system components were detected with immunohistochemistry and immunofluorescence analyses. Specimens were included from 2010 to 2017.SETTING: University Hospital.PATIENTS/PARTICIPANTS: Ovaries and testes from a total of 124 human embryos and fetuses aged 5 to 17 postconception weeks were obtained from healthy women aged 16 to 47 years resident in Denmark or Scotland.MAIN OUTCOME MEASURES: Gene expression analysis using microarray was performed in 46 specimens and qPCR analysis in 56 specimens, both sexes included. Protein analysis included 22 specimens (11 ovaries, 11 testes).RESULTS: IGF system members were detected in embryonic and fetal testes and ovaries, both at gene transcript and protein level. A higher expression of IGF regulators was detected in testes than ovaries, with a preferred localization to Leydig cells.CONCLUSIONS: These data indicate that the IGF system is active during very early gestation, when it may have a regulatory role in Leydig cells.",

keywords = "human gonadal development, IGF signaling, stanniocalcins, PAPP-A, first- and second-trimester gonads",

author = "Mamsen, {Linn Salto} and Zafeiri Aikaterini and B{\o}tkj{\ae}r, {Jane Alr{\o}} and Hardlei, {Jonna Rasmussen} and Erik Ernst and Claus Oxvig and Fowler, {Paul A} and Andersen, {Claus Yding}",

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doi = "10.1210/clinem/dgaa470",

language = "English",

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T1 - Expression of the Insulin-like Growth Factor System in First- and Second-Trimester Human Embryonic and Fetal Gonads

AU - Mamsen, Linn Salto

AU - Aikaterini, Zafeiri

AU - Bøtkjær, Jane Alrø

AU - Hardlei, Jonna Rasmussen

AU - Ernst, Erik

AU - Oxvig, Claus

AU - Fowler, Paul A

AU - Andersen, Claus Yding

PY - 2020/9/1

Y1 - 2020/9/1

N2 - CONTEXT: Insulin-like growth factor (IGF) signaling is crucial for sex differentiation and development of Leydig and Sertoli cells in fetal mice testes. No such information is available for human embryonic and fetal testes and ovaries.OBJECTIVE: To investigate presence and activity of the IGF signaling system during human embryonic and fetal ovarian and testicular development.DESIGN: Human embryonic and fetal gonads were obtained following legal terminations of pregnancies. Gene expression was assessed by microarray and qPCR transcript analyses. Proteins of the IGF system components were detected with immunohistochemistry and immunofluorescence analyses. Specimens were included from 2010 to 2017.SETTING: University Hospital.PATIENTS/PARTICIPANTS: Ovaries and testes from a total of 124 human embryos and fetuses aged 5 to 17 postconception weeks were obtained from healthy women aged 16 to 47 years resident in Denmark or Scotland.MAIN OUTCOME MEASURES: Gene expression analysis using microarray was performed in 46 specimens and qPCR analysis in 56 specimens, both sexes included. Protein analysis included 22 specimens (11 ovaries, 11 testes).RESULTS: IGF system members were detected in embryonic and fetal testes and ovaries, both at gene transcript and protein level. A higher expression of IGF regulators was detected in testes than ovaries, with a preferred localization to Leydig cells.CONCLUSIONS: These data indicate that the IGF system is active during very early gestation, when it may have a regulatory role in Leydig cells.

AB - CONTEXT: Insulin-like growth factor (IGF) signaling is crucial for sex differentiation and development of Leydig and Sertoli cells in fetal mice testes. No such information is available for human embryonic and fetal testes and ovaries.OBJECTIVE: To investigate presence and activity of the IGF signaling system during human embryonic and fetal ovarian and testicular development.DESIGN: Human embryonic and fetal gonads were obtained following legal terminations of pregnancies. Gene expression was assessed by microarray and qPCR transcript analyses. Proteins of the IGF system components were detected with immunohistochemistry and immunofluorescence analyses. Specimens were included from 2010 to 2017.SETTING: University Hospital.PATIENTS/PARTICIPANTS: Ovaries and testes from a total of 124 human embryos and fetuses aged 5 to 17 postconception weeks were obtained from healthy women aged 16 to 47 years resident in Denmark or Scotland.MAIN OUTCOME MEASURES: Gene expression analysis using microarray was performed in 46 specimens and qPCR analysis in 56 specimens, both sexes included. Protein analysis included 22 specimens (11 ovaries, 11 testes).RESULTS: IGF system members were detected in embryonic and fetal testes and ovaries, both at gene transcript and protein level. A higher expression of IGF regulators was detected in testes than ovaries, with a preferred localization to Leydig cells.CONCLUSIONS: These data indicate that the IGF system is active during very early gestation, when it may have a regulatory role in Leydig cells.

KW - human gonadal development

KW - IGF signaling

KW - stanniocalcins

KW - PAPP-A

KW - first- and second-trimester gonads

U2 - 10.1210/clinem/dgaa470

DO - 10.1210/clinem/dgaa470

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C2 - 32726409

SN - 0021-972X

VL - 105

SP - E3157-E3168

JO - The Journal of clinical endocrinology and metabolism

JF - The Journal of clinical endocrinology and metabolism

IS - 9

ER -

Expression of the Insulin-like Growth Factor System in First- and Second-Trimester Human Embryonic and Fetal Gonads

Abstract

Keywords

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