Developmental and hormonal regulation of the expression of oligodendrocyte-specific protein/claudin 11 in mouse testis

The proliferation and differentiation of testicular progenitor stem cells i nto highly specialized germ cells (spermatozoa) are largely controlled by t he hormonally (FSH and testosterone) regulated adjacent supporting Sertoli cells. However, the factors involved in this control remain largely unknown . In the present study, the technique of differential display PCR was used to identify target transcripts to FSH action in cultured murine Sertoli cel ls. Among these target transcripts, we identified the oligodendrocyte-speci fic protein (OSP), also known as claudin 11, which had recently been shown to play a key role in the formation of the hematotesticular barrier. Our da ta show that the testicular expression of OSP is dependent upon male gonad development and systemic and local signaling molecules. Indeed, OSP is expr essed early in fetal development in Sertoli cells, immediately after the pe ak of SRY (sex-determining region, Y gene) expression, but just before that of the anti-Mullerian hormone. Postnatally, OSP expression starts to incre ase from day 3 to reach a plateau between days 6 and 16 postnatally. In the prepubertal and adult testes, an apparent decline in OSP messenger RNA (mR NA) levels was found, probably because of the increasing number of germ cel ls (which do not express OSP). Among the signaling molecules that control t esticular OSP expression, we have identified FSH and tumor necrosis factor- alpha (TNF alpha). Indeed, using a model of purified cultured mouse Sertoli cells, we demonstrate that FSH inhibits, in a dose (ED50 = 4 ng/ml)- and t ime (maximal effect after 24 h)-dependent manner, the levels of OSP mRNA. S uch an inhibitory effect was mimicked by 8-bromo-cAMP, suggesting that FSH may use the cAMP/protein kinase A pathway to inhibit OSP mRNA levels. TNF a lpha was also shown to inhibit OSP expression in cultured Sertoli cells. Th e maximal effect was observed after 48 h of TNF alpha treatment with an ED5 0 of 4.5 ng/ml. Together, our results indicate that OSP expression 1) start s during fetal life at a critical period, probably under SRY control and du ring testicular formation; and 2) is regulated by hormones (FSH) and cytoki nes (TNF alpha) in the adult testis, suggesting a critical role for these m olecules in the (re)modeling process of the haematotesticular barrier durin g spermatogenesis.