Novel scavenger receptor gene is differentially expressed in the embryonic and adult mouse testis.

In an effort to understand the mechanisms that underpin gonadal differentiation at the time of sex determination, we identified a cDNA encoding a putative novel testis expressed scavenger receptor, Tesr. Based on its domain structure, we hypothesize that the function of Tesr is similar to that of other scavenger receptors that play roles in phagocytosis of apoptotic cells, cell-cell adhesion, and defense. Tesr mRNA was detected in fetal mouse gonads of both sexes at 11.5 days post coitum (dpc). From 12.0 dpc, Tesr expression rapidly decreased in the female and was maintained in the male. Expression was seen in embryonic mouse sites other than the testis, such as in brain, eye, head, heart, neural arch, and cartilage primordium. Tesr expression in the newborn testis was faint to undetectable, but it increased from 2 days postpartum (dpp) until 15 dpp and was found in a subset of interstitial cells and in germ and Sertoli cells. Tesr mRNA in the adult mouse testis was observed in Sertoli cells, spermatogonia, spermatocytes, round spermatids, and in a subset of interstitial cells. We conclude that Tesr is differentially expressed in the male vs. female embryonic gonad and is expressed in both the ovary and the testes postnatally after 2 dpp.     

Ultrastructure of developing germ cells in the fetal rabbit testis

Testicular differentiation, as evidenced by the appearance of a distinct tunica albuginea and formation of plate-like aggregates of germ cells and mesenchymal cells, occurs at 16 days in the rabbit fetus. The germ cells at this stage of development are isolated large, round to oval cells that are easily distinguished from the smaller elongated mesenchymal elements surrounding them. The germ cell nuclei have a smooth spherical contour and a prominent eccentric nucleolus. Cytoplasmic organelles are sparse, consisting of scattered polyribosomes and spherical or ovoid mitochondria distributed singly in the cell. At 18 days, the cell groups form into distinct cords of germ cells and supporting cells, the earliest stage of seminiferous tubule formation. Between 22 and 25 days, proliferating germ cells show increasing condensation of nuclear chromatin and increased nucleolar complexity. The cytoplasm contains groups of mitochondria, dense polyribosomal complexes, lipid aggregates, scattered smooth vesicles and prominent Golgi complexes. Intercellular bridges appear between germ cells on day 22 and increase in number on succeeding days. During the last week of fetal development, germ cells become aligned in rows at the periphery of the primitive tubules. Their arrangement at this time resembles that of spermatogonia in the adult testis. However, the fetal “prespermatogonia” lack some of the characteristic ultrastructural features of adult spermatogonia.     

Atypical germ cells of the testis

Summary It is uncertain whether the so called intratubular atypical germ cells (carcinoma in situ cells) demonstrable in the testicular tissue around different germ cell tumors and in testicular biopsies of patients with impaired fertility are identical with regard to their morphology and further development. Thus atypical germ cells of 18 patients with testicular germ cell tumors and of 3 patients with atypical germ cells in testicular biopsies without tumor were studied by electron microscopy and/or by immunohistochemistry. The atypical germ cells show characteristic alterations distinguishing them from normal germ cells, especially spermatogonia. However, there are no differences between atypical germ cells in the above mentioned groups. Immunohistochemical reactions are negative with anti-alpha-fetoprotein and anti-beta-human-chorionic-gonadotropin, but 6 of the 15 cases are positive with antiferritin. However, this positive reaction occurs in cases in different diagnostic groups. Atypical germ cells of the different groups cannot be distinguished by electron microscopy or immunohistochemical methods, but further investigations vestigations, including cell cultures, may provide more information.     

Immunohistochemical markers of carcinoma in situ of the testis also expressed in normal infantile germ cells

Carcinoma in situ of the testis is an intratubular, pre-invasive lesion preceding germ cell tumour. In adult men, carcinoma in situ cells differ in several aspects from normal germ cells. For example, placental-like alkaline phosphatase and/or the epitopes for the monoclonal antibodies M2A, 43-9F and TRA-1–60 are not seen in normal germ cells, whereas their presence is considered a specific sign of carcinoma in situ . As it is known that placental-like alkaline phosphatase and the epitope for TRA-1–60 are expressed in normal fetal germ cells it is possible that the markers could appear in normal infantile germ cells in a period after birth before they lose their expression. In children, carcinoma in situ cells may be difficult to identify morphologically and the use of the markers could be of great value. However, little information is available on the expression of the markers of adult carcinoma in situ in normal infantile germ cells. We investigated gonads from 66 boys less than 15 years old who died suddenly. Their deaths were unrelated to testicular disease. Immunohistochemical staining with anti-placental-like alkaline phosphatase antibody and monoclonal antibodies TRA-1–60 and 43–9F were performed. We found that these markers were expressed in some normal infantile germ cells until the age of 1 year. Therefore, these markers are not suitable for diagnosis of carcinoma in situ during the early postnatal period of life. Furthermore, our findings of placental-like alkaline phosphatase and the epitope for TRA-1–60 in normal germ cells before birth indicate that the markers of adult carcinoma in situ cells are of embryonic origin. This is in accordance with the hypothesis that carcinoma in situ cells are fetal germ cells malignantly transformed during fetal life, although re-expression of the antigens could provide an alternative explanation.     

Dll3 is expressed in developing hair cells in the mammalian cochlea.

Notch mediates the process of lateral inhibition that controls the production of hair cells in the inner ear. Hair cells are known to express Notch ligands Dll1 and Jag2, which signal through Notch1 in adjacent supporting cells. However, recent genetic and pharmacological studies indicate that the level of Notch-mediated lateral inhibition is greater than can be accounted for by Dll1 and Jag2. Here, we report that another Notch ligand, Dll3, is expressed in developing hair cells, in a pattern that overlaps that of Dll1 and Jag2. We analyzed the cochleae of Dll3(pu) mutant mice, but did not detect any abnormalities. However, earlier studies have demonstrated that there is functional redundancy among Notch ligands in cochlear development and loss of one ligand can be at least partially compensated for by another. Thus Dll3 may play a role in lateral inhibition similar to that of Dll1 and Jag2.     

The LIM domain-containing homeo box gene Xlim-1 is expressed specifically in the organizer region of Xenopus gastrula embryos.

A novel cysteine-rich motif, named LIM, has been identified in the homeo box genes lin-11, Isl-1, and mec-3; the mec-3 and lin-11 genes determine cell lineages in Caenorhabditis elegans. We isolated LIM class homeo box genes from Xenopus laevis that are closely related to lin-11 and mec-3 in the LIM and homeo domains. This paper deals with one of these genes, Xlim-1. Xlim-1 mRNA is found at low abundance in the unfertilized egg, has a major expression phase at the gastrula stage, decreases, and rises again during the tadpole stage. In adult tissues the brain shows the highest abundance, by far, of Xlim-1 mRNA. The maternal and late expression phases of the Xlim-1 gene suggest that it has multiple functions at different stages of the Xenopus life cycle. In the gastrula embryo, Xlim-1 mRNA is localized in the dorsal lip and the dorsal mesoderm, that is, in the region of Spemann's organizer. Explant experiments showed that Xlim-1 mRNA is induced by the mesoderm-inducer activin A and by retinoic acid, which is not a mesoderm inducer but affects patterning during Xenopus embryogenesis; application of activin A and retinoic acid together results in synergistic induction. The structure, inducibility, and localized expression in the organizer of the Xlim-1 gene suggest that it has a role in establishing body pattern during gastrulation.