Expression of the Insulin-like Growth Factor System in First- and Second-Trimester Human Embryonic and Fetal Gonads
Linn Salto Mamsen, Aikaterini Zafeiri, Jane Alrø Bøtkjær, Jonna Rasmussen Hardlei, Erik Ernst, Claus Oxvig, Paul 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.