Insufficient androgen and FSH signaling may be responsible for the azoospermia of the infantile primate testes despite exposure to an adult-like hormonal milieu.
BACKGROUND
In humans, as well as in other higher primates, the infantile testis is exposed to an adult-like hormonal milieu, but spermatogenesis is not initiated at this stage of primate development. In the present study, we examined the molecular basis of this intriguing infertile state of the primate testis.


METHODS
The integrity of androgen receptor (AR) and FSH receptor (FSHR) signaling pathways in primary cultures of Sertoli cells (Scs) harvested from azoospermic infant and spermatogenic pubertal monkey testes were investigated under identical in vitro hormonal conditions. In order to synchronously harvest Scs from early pubertal testis, the activation of testicular puberty was timed experimentally by prematurely initiating gonadotrophin secretion in juvenile animals with an intermittent infusion of gonadotrophin-releasing hormone.


RESULTS
While qRT-PCR demonstrated that AR and FSHR mRNA expression in Scs from infant and pubertal testes were comparable, androgen-binding and FSH-mediated cAMP production by infant Scs was extremely low. Compromised AR and FSHR signaling in infant Scs was further supported by the finding that testosterone (T) and FSH failed to augment the expression of the T responsive gene, claudin 11, and the FSH responsive genes, inhibin-βB, stem cell factor (SCF) and glial cell line-derived neurotrophic factor (GDNF) in Scs harvested at this stage of development.


CONCLUSIONS
These results indicate that compromised AR and FSHR signaling pathways in Scs underlie the inability of the infant primate testis to respond to an endogenous hormonal milieu that later in development, at the time puberty, stimulates the initiation of spermatogenesis. This finding may have relevance to some forms of idiopathic infertility in men.
Division of Cellular Endocrinology, National Institute of Immunology, New Delhi 110067, India. planttm@mwri.magee.edu
Subeer S
SS
Majumdar
Kanchan
K
Sarda
Indrashis
I
Bhattacharya
Tony M
TM
Plant
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D053713:Azoospermia / Q000378:metabolism*; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D008024:Ligands; D008253:Macaca mulatta; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D011962:Receptors, FSH / Q000378:metabolism; D012708:Sertoli Cells / Q000378:metabolism; D013091:Spermatogenesis; D013737:Testis / Q000254:growth & development* / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism; D013997:Time Factors
D000728:Androgens; D008024:Ligands; D012333:RNA, Messenger; D011944:Receptors, Androgen; D011962:Receptors, FSH; D013739:Testosterone; D005640:Follicle Stimulating Hormone