This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Berensztein, E. B. Articles by Belgorosky, A. Search for Related Content PubMed PubMed Citation Articles by Berensztein, E. B. Articles by Belgorosky, A.

Apoptosis and Proliferation of Human Testicular Somatic and Germ Cells during Prepuberty: High Rate of Testicular Growth in Newborns Mediated by Decreased Apoptosis

Research Laboratory, Garrahan Pediatric Hospital, Buenos Aires 1245, Argentina

Address all correspondence and requests for reprints to: Alicia Belgorosky, Hospital de Pediatria Garrahan, C. de los Pozos 1881, Buens Aires 1245, Argentina. E-mail: abelgo{at}elsitio.net.

Abstract

Programmed cell death and proliferation are evolutionary conserved processes that play a major role during normal development and homeostasis. In the testis, during the fetal and newborn periods, they might determine final adult size and fertility potential. In the present study, we have measured the relative number of testicular cells in apoptosis and in active proliferation in the seminiferous cords and in the interstitium, at different age periods of prepubertal testicular development in humans. Testes from 44 prepubertal subjects without endocrine and metabolic abnormalities were collected at necropsy. They were divided in three age groups (Gr): Gr 1, newborn (1- to 21-d-old neonates), n = 18, mean (±SD) age 0.3 ± 0.23 months; Gr 2, post natal activation (1- to 6-month-old infants), n = 13, mean age 3.93 ± 1.90 months; and Gr 3, early childhood period (1- to <6-yr-old boys), n = 13, mean age 31.5 ± 18.9 months. Apoptosis was detected in 5-µm tissue sections using a modified terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay and cell proliferation was assessed by Ki-67 immunohistochemistry. Evaluation of apoptosis was confirmed by estimation of active caspase-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. In Gr 1, there was a significant positive correlation between age and testis weight (P = 0.02).

Mean (±SD) germ cell apoptotic index, AI, (% of apoptotic cells out 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 was 6.60 ± 4.07, 22.0 ± 14.0 and 27.5 ± 19.8, respectively. In interstitial cells, 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 than in Gr 2 or Gr 3 (P < 0.05). Mean (±SD) germ cell proliferation index, PI, was 18.6 ± 13.0, 10.0 ± 6.50 and 10.9 ± 6.24% in Gr 1, Gr 2, and Gr 3, respectively. In Sertoli cells and in interstitial cells PI was similar in the three age groups. The PI/AI ratio was used to compare relative differences among age groups. The PI/AI ratio of germ cells, Sertoli cells and interstitial cells in Gr 1 was significantly higher than in Gr 2 or Gr 3 (P < 0.05). It is concluded that, in normal subjects, there is a vigorous growth of the testis during the newborn period with subsequent stabilization during the first years of prepuberty. This cell growth seems to be mainly mediated by decreased apoptosis. The factors that modulate apoptosis of testicular cells are not known, but it is remarkable that this change takes place before the testosterone peak of the post natal gonadal activation of the first trimester of life. These changes taking place during the newborn period might be important to define testicular function in adults.

This article has been cited by other articles:

				P. Bougneres, M. Francois, L. Pantalone, D. Rodrigue, C. Bouvattier, E. Demesteere, D. Roger, and N. Lahlou Effects of an Early Postnatal Treatment of Hypogonadotropic Hypogonadism with a Continuous Subcutaneous Infusion of Recombinant Follicle-Stimulating Hormone and Luteinizing Hormone J. Clin. Endocrinol. Metab., June 1, 2008; 93(6): 2202 - 2205. [Abstract] [Full Text] [PDF]

				I. Bergada, C. Milani, P. Bedecarras, L. Andreone, M. G. Ropelato, S. Gottlieb, C. Bergada, S. Campo, and R. A. Rey Time Course of the Serum Gonadotropin Surge, Inhibins, and Anti-Mullerian Hormone in Normal Newborn Males during the First Month of Life J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 4092 - 4098. [Abstract] [Full Text] [PDF]

				D. R. Holsberger, S. E. Kiesewetter, and P. S. Cooke Regulation of Neonatal Sertoli Cell Development by Thyroid Hormone Receptor {alpha}1 Biol Reprod, September 1, 2005; 73(3): 396 - 403. [Abstract] [Full Text] [PDF]

				M. M. Grumbach A Window of Opportunity: The Diagnosis of Gonadotropin Deficiency in the Male Infant J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 3122 - 3127. [Abstract] [Full Text] [PDF]

				T. M. Said, U. Paasch, H.-J. Glander, and A. Agarwal Role of caspases in male infertility Hum. Reprod. Update, January 1, 2004; 10(1): 39 - 51. [Abstract] [Full Text] [PDF]

				D. R. Simorangkir, G. R. Marshall, and T. M. Plant Sertoli Cell Proliferation during Prepubertal Development in the Rhesus Monkey (Macaca mulatta) Is Maximal during Infancy when Gonadotropin Secretion Is Robust J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4984 - 4989. [Abstract] [Full Text] [PDF]