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The precise timing and sequence of changes in expression of key genes and proteins during human sex-differentiation and onset of steroidogenesis was evaluated by whole-genome expression in 67 first trimester human embryonic and fetal ovaries and testis and confirmed by qPCR and immunohistochemistry (IHC).  SRY/SOX9  expression initiated in testis around day 40 pc, followed by initiation of  AMH  and steroidogenic genes required for androgen production at day 53 pc. In ovaries, gene expression of  RSPO1, LIN28 ,  FOXL2, WNT2B , and  ETV5 , were significantly higher than in testis, whereas  GLI1  was significantly higher in testis than ovaries. Gene expression was confirmed by IHC for GAGE, SOX9, AMH, CYP17A1, LIN28, WNT2B, ETV5 and GLI1. Gene expression was not associated with the maternal smoking habits. Collectively, a precise temporal determination of changes in expression of key genes involved in human sex-differentiation is defined, with identification of new genes of potential importance.

Temporal expression pattern of genes during the period of sex differentiation in human embryonic gonads