Accelerated germ cell apoptosis in sex chromosome aneuploid fetal human gonads

Abstract

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.

Potential Ameliorative Role of N-Acetylcysteine Against Testicular Dysfunction Induced by Titanium Dioxide in Male Albino Rats

“…Administration of TiO2 for 3 months upregulated BcL2 expression and NAC down regulate it confirming antiapoptotic activity of NAC as reported by ours and findings of (Aggarwal et al, 2010). Germ cell apoptosis play an important role in normal testicular function (Modi et al, 2003). It is required for normal spermatogenesis and is believed to ensure cellular homeostasis and maintain the balance between germ cells and Sertoli cells (Said et al, 2004).…”

Ontogeny and cellular localization of SRY transcripts in the human testes and its detection in spermatozoa

“…These tissues were collected after informed consent and were a part of previous studies (Modi 2001, Modi et al 2003a, 2003b, Shah et al 2005.…”

“…The collection of the fetal samples has been detailed previously (Modi et al 2003b). Normal human fetal gonads were collected from legal abortions done at the Obstetric and Gynecology Department of KEMH.…”

“…Testes from all fetuses were immediately fixed in 10% buffered formaldehyde for 24 h and processed for routine paraffin embedding and sectioning as described previously (Modi et al 2003b); at all stages, care was taken to avoid RNAse contamination. Sections 5 mm thick were mounted on 3-aminopropyltriethoxysilane-coated, nuclease-free glass slides and dried at 37 8C for 24 h prior to use.…”

“…The cells were washed in RNase-free water and dehydrated. Florescent ISH was carried out as described previously (Modi et al 1999, Modi et al 2003a, 2003b. Briefly, 2 mg/ml of the probe were diluted in a hybridization cocktail (50% formamide, 4 £ SSC, 10% dextran sulfate, 0.25% yeast tRNA and 0.25% herring sperm DNA) and applied to the slides.…”