The Fate of Spermatogonial Stem Cells in the Cryptorchid Testes of RXFP2 Deficient Mice

The environmental niche of the spermatogonial stem cell pool is critical to ensure the continued generation of the germ cell population. To study the consequences of an aberrant testicular environment in cryptorchidism we used a mouse model with a deletion of Rxfp2 gene resulting in a high intra-abdominal testicular position. Mutant males were infertile with the gross morphology of the cryptorchid testis progressively deteriorating with age. Few spermatogonia were identifiable in 12 month old cryptorchid testes. Gene expression analysis showed no difference between mutant and control testes at postnatal day 10. In three month old males a decrease in expression of spermatogonial stem cell (SSC) markers Id4, Nanos2, and Ret was shown. The direct counting of ID4+ cells supported a significant decrease of SSCs. In contrast, the expression of Plzf, a marker for undifferentiated and differentiating spermatogonia was not reduced, and the number of PLZF+ cells in the cryptorchid testis was higher in three month old testes, but equal to control in six month old mutants. The PLZF+ cells did not show a higher rate of apoptosis in cryptorchid testis. The expression of the Sertoli cell FGF2 gene required for SSC maintenance was significantly reduced in mutant testis. Based on these findings we propose that the deregulation of somatic and germ cell genes in the cryptorchid testis, directs the SSCs towards the differentiation pathway. This leads to a depletion of the SSC pool and an increase in the number of PLZF+ spermatogonial cells, which too, eventually decreases with the exhaustion of the stem cell pool. Such a dynamic suggests that an early correction of cryptorchidism is critical for the retention of the SSC pool.

Composition date of the synoptic gospels

The purpose of this research paper is to follow a line of ongoing investigations that discuss dates for the origin of the synoptic gospels and evaluate the arguments for early, late, and intermediate dating and their susceptibility to critique from opposing arguments. There are three principal components in dating theories: (1) data from the Greek in the earliest texts (2) data concerning the provenance of the earliest texts (3) and data from the historical context of the first century. The study is significant because, contrary to what might be expected, the starting and key point in deciding on a composition date is the Book of Acts of the Apostles. This study compiled and integrated information, in an unbiased fashion, based on reading and researching large numbers of texts by scholars, such as Hengel, who support an earlier dating, as well as those, such as Fitzmyer, who support a later dating. Furthermore, this study also required knowledge of those scholars who propose dates that do not fall into these main categories. The research demonstrated that by looking at the Book of Acts of the Apostles as the key starting point, the synoptic gospels were most likely composed before 70 CE, therefore, supporting scholars who argue for an earlier date.