Accelerated germ cell apoptosis in sex chromosome aneuploid fetal human gonads

The purpose of the study was to examine the occurrence of programmed cell death (apoptosis) in normal and chromosomally aneuploid testis and ovaries during the second trimester of human development. Such information may be useful in understanding normal and abnormal germ cell development and disorders associated with infertility in adult life. Apoptosis was studied by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) analysis in human fetal ovaries (n = 16) and testis (n = 14) between 9 and 23 weeks of development, in ovaries of four Turner's syndrome fetuses (45X) and in the gonad of an XO/XY fetus. In normal fetal testis, a small proportion of germ cells, Sertoli cells and Leydig cells undergo apoptosis. In normal fetal ovaries, some developing oocytes and granulosa cells were detected as TUNEL positive. Semiquantitative analysis of fetal ovaries revealed that approximately 3-7% of oocytes were apoptotic. In abnormal fetal testis (XO/XY genotype). TUNEL analysis revealed that only germ cells not enclosed in seminiferous tubules undergo apoptosis. TUNEL analysis of the Turner's syndrome (45X) ovaries studied at 15 and 20 weeks of development revealed massive apoptosis of the oocytes. Nearly 50-70% of the oocytes were TUNEL positive in these ovaries. These results suggest that germ cell apoptosis is a common event occurring during development of human gonads. Chromosomal defects by some means accelerates apoptosis that probably leads to gonadal dysgenesis later in life.