Apoptosis and Proliferation of human testicular somatic and germ cells during prepuberty: high rate of testicular growth in newborns mediated by decreased apoptosis.

BERENSZTEIN E,; SCIARA M,; RIVAROLA MA,; BELGOROSKY, A

Journal of Clinical Endocrinology and Metabolism

The Endocrine Society

Lugar: Chevy Chase; Año: 2002 vol. 87 p. 5113 - 5118

0021-972X

Programmed cell death and proliferation are evolutionaryconserved processes that play a major role during normaldevelopment and homeostasis. In the testis, during the fetaland newborn periods, they might determine final adult sizeand fertility potential. In the present study,wehave measuredthe relative number of testicular cells in apoptosis and inactive proliferation in the seminiferous cords and in the interstitium,at different age periods of prepubertal testiculardevelopment in humans. Testes from 44 prepubertal subjectswithout endocrine and metabolic abnormalities were collectedat necropsy. They were divided in three age groups(Gr):Gr1, newborn (1- to 21-d-old neonates),n18,mean(SD)age 0.3 0.23 months; Gr 2, post natal activation (1- to6-month-old infants), n 13, mean age 3.93 1.90 months; andGr 3, early childhood period (1- to<6-yr-old boys),n13,meanage 31.5 18.9 months. Apoptosis was detected in 5-m tissuesections using a modified terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay and cell proliferationwas assessed by Ki-67 immunohistochemistry. Evaluationof apoptosis was confirmed by estimation of activecaspase-3. Mean (SD) testicular weight was 0.38 0.20, 0.54 0.35, and 0.51 0.11 g in Gr 1, Gr 2, and Gr 3, respectively. InGr 1, there was a significant positive correlation between ageand testis weight (P 0.02).Mean (SD) germ cell apoptotic index, AI, (% of apoptotic cellsout of total cell number) was 15.0 6.60, 27.0 8.80 and 33.4 11.4 in Gr 1, Gr 2, and Gr 3, respectively. In Sertoli cells, it was6.604.07, 22.014.0 and 27.519.8, respectively. In interstitialcells, it was 10.2 6.38, 18.0 6.70 and 25.7 15.5, respectively.In the three types of cells, AI in Gr 1 was significantly lower thanin Gr 2 or Gr 3 (P < 0.05). Mean (SD) germ cell proliferationindex, PI, was 18.613.0, 10.06.50 and 10.96.24% in Gr 1, Gr2, and Gr 3, respectively. In Sertoli cells and in interstitial cellsPI was similar in the three age groups. The PI/AI ratio was usedto compare relative differences among age groups. The PI/AIratio of germ cells, Sertoli cells and interstitial cells in Gr 1 wassignificantly higher than inGr2 orGr3 (P<0.05). It is concludedthat, in normal subjects, there is a vigorous growth of the testisduring the newborn period with subsequent stabilization duringthe first years of prepuberty. This cell growth seems to bemainly mediated by decreased apoptosis. The factors that modulateapoptosis of testicular cells are not known, but it is remarkablethat this change takes place before the testosteronepeak of the post natal gonadal activation of the first trimester oflife. These changes taking place during the newborn periodmight be important to define testicular function in adults.(J Clin Endocrinol Metab 87: 5113?5118, 2002