Background: R-Spondin1 (Rspo1) is a novel regulator of the Wnt/β-catenin signalling pathway. Loss-of-function mutations in human RSPO1 cause testicular differentiation in 46, XX females, pointing to a role in ovarian development. Here we report the cloning and comparative expression analysis of R-SPONDIN1 orthologues in the mouse, chicken and red-eared slider turtle, three species with different sex-determining mechanisms. Evidence is presented that this gene is an ancient component of the vertebrate ovary-determining pathway.
Sex determination in vertebrates, the process of forming an ovary or testis from a bipotential gonad, can be initiated by genetic or environmental factors. Elements of the downstream molecular pathways underlying these different sex-determining mechanisms have been evolutionarily conserved. We find the first evidence that Sox9 expression is preferentially organized in the testis early in the temperature-sensitive period in a species with temperature-dependent sex determination (Trachemys scripta). This pattern occurs before sexually dimorphic Mis expression and in a temporal hierarchy that is similar to mammals. Furthermore, we extend previous findings that Dmrt1 expression at early stages of sex determination has a dimorphic pattern consistent with a possible upstream role in determining the fate of the bipotential gonad.
Gonadogenesis, the process of forming an ovary or a testis from a bipotential gonad, is critical to the development of sexually reproducing adults. Although the molecular pathway underlying vertebrate gonadogenesis is well characterized in organisms exhibiting genotypic sex determination, it is less well understood in vertebrates whose sex is determined by environmental factors. We examine the response of six candidate sex-determining genes to sex-reversing temperature shifts in a species with temperature-dependent sex determination (TSD). For the first time, we report the regulation of FoxL2, Wnt4, Dmrt1, and Mis by temperature, confirming their involvement in the molecular pathway underlying TSD and placing them downstream of the action of temperature. We find evidence that FoxL2 plays an ovarian-specific role in development, whereas Wnt4 appears to be involved in both testis and ovary formation. Dmrt1 expression shows rapid activation in response to a shift to male-producing temperature, whereas Mis up-regulation is delayed. Furthermore, early repression of Mis appears critical to ovarian development. We also investigate Dax1 and Sox9 and reveal that at the level of gene expression, response to temperature is comparatively later in gonadogenesis. By examining the role of these genes in TSD, we can begin to elucidate elements of conservation and divergence between sex-determining mechanisms.
There is a high incidence of infertility in males following traumatic spinal cord injury (SCI). Quality of semen is frequently poor in these patients, but the pathophysiological mechanism(s) causing this are not known. Blood-testis barrier (BTB) integrity following SCI has not previously been examined. The objective of this study was to characterize the effects of spinal contusion injury on the BTB in the rat. 63 adult, male Sprague Dawley rats received SCI (n = 28), laminectomy only (n = 7) or served as uninjured, age-matched controls (n = 28). Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), BTB permeability to the vascular contrast agent gadopentate dimeglumine (Gd) was assessed at either 72 hours-, or 10 months post-SCI. DCE-MRI data revealed that BTB permeability to Gd was greater than controls at both 72 h and 10 mo post-SCI. Histological evaluation of testis tissue showed increased BTB permeability to immunoglobulin G at both 72 hours- and 10 months post-SCI, compared to age-matched sham-operated and uninjured controls. Tight junctional integrity within the seminiferous epithelium was assessed; at 72 hours post-SCI, decreased expression of the tight junction protein occludin was observed. Presence of inflammation in the testes was also examined. High expression of the proinflammatory cytokine interleukin-1 beta was detected in testis tissue. CD68+ immune cell infiltrate and mast cells were also detected within the seminiferous epithelium of both acute and chronic SCI groups but not in controls. In addition, extensive germ cell apoptosis was observed at 72 h post-SCI. Based on these results, we conclude that SCI is followed by compromised BTB integrity by as early as 72 hours post-injury in rats and is accompanied by a substantial immune response within the testis. Furthermore, our results indicate that the BTB remains compromised and testis immune cell infiltration persists for months after the initial injury.
Purpose To evaluate discrepancies in doses per bottle, bottle fill volume, and cost among branded and generic formulations of latanoprost Design Comparative economic analysis Methods This study was conducted at the Ruiz Department of Ophthalmology and Visual Science at The University of Texas Health Science Center at Houston (UTHealth). Four regionally available latanoprost formulations were measured. Number of drops per bottle and actual bottle fill volume were measured for a calculated sample size (10 bottles). Annual cost (using average wholesale price), days use per bottle, drops per milliliter, and number of bottles used per year were calculated. Data were summarized using mean and standard deviation; one-way analysis of variance and post hoc Tukey's studentized range test were used for comparing means among manufactures. Results Pfizer's branded lantanoprost, Xalatan (New York, NY), had the largest fill volume (P<0.001). Pfizer had the highest yearly cost at $1,198 (P<0.001) whereas Akorn (Lake Forest, IL) and Bausch & Lomb (Rochester, NY) had the lowest ($184 and $201, respectively). Pfizer and Bausch & Lomb had the most drops per bottle (87.3 and 88.7, respectively), which was statistically more (P<0.001) than either Akorn or Sandoz (Princeton, NJ) (77.6 and 76.6, respectively) but there was no statistical difference among the standard deviation of drops per bottle (Levene 0.14). Conclusions Annual cost and number of doses per bottle, factors important to patients, vary significantly depending on manufacturer of latanoprost. Practitioners can better advise patients being aware of these differences.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.