Expression of the Insulin-like Growth Factor system in first and second trimester human embryonic and fetal gonads

Linn Salto Mamsen* (Corresponding Author), Aikaterini Zafeiri, Jane Alrø Bøtkjær, Jonna Hardlei Rasmussen, Erik Ernst, Claus Oxvig, Paul A. Fowler , Claus Yding Andersen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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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 languageEnglish
Article numberdgaa470
Pages (from-to)E3157-E3168
Number of pages12
JournalJournal of Clinical Endocrinology and Metabolism
Issue number9
Early online date29 Jul 2020
Publication statusPublished - Sept 2020

Bibliographical note

Financial Support: This work was supported by The Medical Research Council [MR/L010011/1 to PAF] and the European Community's Seventh Framework Programme (FP7/2007-2013) [under grant agreement no 212885 to PAF], BBSRC/EASTBIO (to AZ), ESHRE supported the ReproUnion fellowship (to AZ), Rigshospitalets Forskningspuljer (to LSM), and ReproUnion 1.0 (to LSM).

Marianne Sguazzino is acknowledged for excellent technical assistance. Gabriela Gudbergsen is acknowledged for her excellent design of Fig. 1.

Data Availability: The dataset generated and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request. Microarray data are available with the Array Express accession number: E-MTAB-5611


  • Human gonadal development
  • IGF signaling
  • stanniocalcins
  • PAPP-A
  • first and second trimester gonads
  • human gonadal development
  • first- and second-trimester gonads
  • I IGF-I
  • GENE
  • First-
  • Second-trimester gonads
  • Stanniocalcins


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