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Mice that are ets variant gene 5 (ETV5) null (Etv5(-/-)) undergo the first wave of spermatogenesis but lose all spermatogonial stem cells (SSCs) during this time. The SSC loss in Etv5(-/-) mice begins during the neonatal period, suggesting a role for ETV5 in SSC self-renewal during this period. Herein, we show that Etv5 mRNA was present in perinatal mouse testis and that ETV5 was expressed in fetal Sertoli cells and by germ cells and Sertoli cells during the neonatal period. Transplantation of Etv5(-/-) germ cells failed to establish spermatogenesis in W/W(v) mice testes, indicating that germ cell ETV5 has a key role in establishment or self-renewal of transplanted SSCs. The SSC self-renewal is stimulated by glial cell-derived neurotrophic factor (GDNF) acting through the RET/GDNF family receptor alpha 1 (GFRA1) receptor complex in SSCs. Immunohistochemistry, quantitative PCR, and laser capture microdissection revealed decreased RET mRNA and protein expression in spermatogonia of neonatal Etv5(-/-) mice by Postnatal Days 4-8, indicating that disrupted GDNF/RET/GFRA1 signaling may occur before initial spermatogonial stem/progenitor cell decrease. Etv5(-/-) spermatogonia had reduced proliferation in vivo and in vitro. Decreased cell proliferation may cause the observed decreases in the number of type A spermatogonia (Postnatal Day 17) and daily sperm production (Postnatal Day 30) in Etv5(-/-) mice, indicating quantitative impairments in the first wave of spermatogenesis. In conclusion, ETV5 is expressed beginning in fetal Sertoli cells and can potentially have effects on neonatal Sertoli cells and germ cells. In addition, ETV5 has critical effects on neonatal spermatogonial proliferation, which may involve impaired signaling through the RET receptor.

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The transcription factor Ets-variant gene 5 (ETV5) is essential for spermatogonial stem cell (SSC) self-renewal, as the targeted deletion of the Etv5 gene in mice (Etv5(-/-)) results in only the first wave of spermatogenesis. Reciprocal transplants of neonatal germ cells from wild-type (WT) and Etv5(-/-) testes were performed to determine the role of ETV5 in Sertoli cells and germ cells. ETV5 appears to be needed in both cell types for normal spermatogenesis. In addition, Etv5(-/-) recipients displayed increased interstitial inflammation and tubular involution after transplantation. Preliminary studies suggest that the blood-testis barrier (Sertoli-Sertoli tight junctional complex) is abnormal in the Etv5(-/-) mouse.

Oxytocin (OT) stimulates phosphoinositide (PI) hydrolysis and prostaglandin (PG) F2 alpha secretion from the endometrium of cyclic pigs, but the presence of specific endometrial receptors for OT has not been demonstrated in this species. Two experiments were performed to detect the presence of functional OT receptors on endometrium collected 15 days post estrus from cyclic gilts. OT receptor density and Kd were determined by receptor assay and Scatchard analysis. Hydrolysis of PI (i.e., incorporation of [3H]inositol into total inositol phosphates) and PGF2 alpha secretion were studied with use of incubations of endometrial explants. Concentrations of PGF2 alpha were log-transformed for analysis of variance and are expressed as means +/- standard error of log-transformed data. In experiment 1, mean density and mean Kd of OT receptors on endometrium of gilts were 29.2 +/- 5.54 fmol/mg protein and 1.59 +/- 0.23 nM, respectively. OT receptor density was significantly correlated with the ability of 100 nM OT to stimulate PI hydrolysis (r = 0.83, p < 0.05) and PGF2 alpha secretion (r = 0.87, p < 0.10), but was not highly correlated with receptor Kd (r = -0.08, p = 0.85). In contrast, OT receptor Kd was not highly correlated with OT-stimulated PI hydrolysis (r = -0.19, p = 0.68) or OT-stimulated PGF2 alpha secretion (r = 0.14, p = 0.86). OT-stimulated PI hydrolysis was also significantly correlated (r = 0.80, p < 0.05) with OT-stimulated PGF2 alpha secretion.(ABSTRACT TRUNCATED AT 250 WORDS)