Spermatogenesis relies on communication between developing germ cells and the supporting Sertoli cells. It is clear that cytokines play an important role in modulating spermatogenesis under normal physiological conditions and in response to infection. However, the regulation of cytokine production within the murine seminiferous epithelium has not yet been well characterised.
Primary cultures of Sertoli cells from 16 day-old mice expressed interleukin (IL)1α, IL1β, IL6, interferon (IFN)1β, tumour necrosis factor (TNF), and activin βA. Treatment with lipopolysaccharide (LPS; TLR4 ligand) increased expression of IL1β (300-fold), IL1α (18-fold), IL6 (80-fold), TNF (60-fold) and activin βA (15-fold) within 3h. Pam3cys (TLR2 ligand) induced similar, although smaller, responses. Poly(I:C) (TLR3 ligand) stimulated IFN1β expression, but only 3-fold, and the response was delayed (>12h culture).
Purified subsets of freshly-isolated germ cells were found to contain mRNA encoding IL1α (highest in pachytene spermatocytes), IL1β (highest in round spermatids), and IL6. Unlike the Sertoli cells, germ cells did not respond to TLR pathway activation by increasing cytokine expression.
In co-cultures of Sertoli and purified germ cells, pachytene spermatocytes inhibited activin βA and βB subunit expression, round spermatids had a smaller effect, and residual bodies slightly inhibited the βA subunit.
The data indicate that murine Sertoli cells respond most strongly to TLR4 and TLR2 activation, producing multiple cytokines, including the activin A subunit, but show poor responsiveness to TLR3 activation. Pachytene spermatocytes preferentially expressed IL1α, and round spermatids preferentially expressed IL1β, indicating a switch in expression patterns during meiosis from the intracellular to the secreted form of IL1. Pachytene spermatocytes, in particular, inhibited activin βA and βB subunit expression in co-cultures, and may play a regulatory role in activin production during the spermatogenic cycle. Furthermore, the regulation of Sertoli cell cytokine expression by residual bodies in the mouse requires further investigation.