title: Developmental changes in human fetal testicular cell numbers and messenger ribonucleic acid levels during the second trimester.
abstract: BACKGROUND
  Normal fetal testis development is essential for masculinization and subsequent adult fertility. The second trimester is a critical period of human testicular development and masculinization, but there is a paucity of reliable developmental data.
  
  
  OBJECTIVE
  The objective of the study was to analyze second-trimester human testicular morphology and function.
  
  
  METHODS
  This was an observational study of second-trimester testis development.
  
  
  METHODS
  The study was conducted at the Universities of Glasgow and Aberdeen.
  
  
  METHODS
  Testes were collected from 57 morphologically normal fetuses of women undergoing elective termination of normally progressing pregnancies (11-19 wk gestation).
  
  
  METHODS
  Testicular morphology, cell numbers, and quantitative expression of 22 key testicular genes were determined.
  
  
  RESULTS
  Sertoli cell and germ cell number increased exponentially throughout the second trimester. Leydig cell number initially increased exponentially but slowed toward 19 wk. Transcripts encoding Sertoli (KITL, FGF9, SOX9, FSHR, WT1) and germ (CKIT, TFAP2C) cell-specific products increased per testis through the second trimester, but expression per cell was static apart from TFAP2C, which declined. Leydig cell transcripts (HSD17B3, CYP11A1, PTC1, CYP17, LHR, INSL3) also remained static per cell. Testicular expression of adrenal transcripts MC2R, CYP11B1, and CYP21 was detectable but unchanged. Expression of other transcripts known or postulated to be involved in testicular development (GATA4, GATA6, CXORF6, WNT2B, WNT4, WNT5A) increased significantly per testis during the second trimester.
  
  
  CONCLUSIONS
  The second trimester is essential for the establishment of Sertoli and germ cell numbers. Sertoli and Leydig cells are active throughout the period, but there is no evidence of changing transcript levels.
authors.affiliation: Division of Cell Sciences, University of Glasgow Veterinary School, Bearsden Road, Glasgow G61 1QH, United Kingdom. p.j.o'shaughnessy@vet.gla.ac.uk
authors.forename: P J
authors.initials: PJ
authors.lastname: O'Shaughnessy
authors.forename: P J
authors.initials: PJ
authors.lastname: Baker
authors.forename: A
authors.initials: A
authors.lastname: Monteiro
authors.forename: S
authors.initials: S
authors.lastname: Cassie
authors.forename: S
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: P A
authors.initials: PA
authors.lastname: Fowler
mesh_terms: D000328:Adult; D002452:Cell Count; D005260:Female; D015870:Gene Expression / Q000502:physiology; D005854:Germ Cells / Q000378:metabolism; D006801:Humans; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D012708:Sertoli Cells / Q000378:metabolism; D013737:Testis / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D011506:Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D013739:Testosterone