Background: Cryptorchidism represents the most common endocrine disease in boys, with infertility frequently observed in unilateral as well as bilateral forms. In this study, we examined the role of Ad (dark) spermatogonia for fertility in cryptorchid boys. The hypothesis to be proven was that boys lacking Ad spermatogonia will develop infertility despite a successful orchidopexy at an early age. Methods: To estimate total sperm count, one of the most predictive parameters of male fertility, we analyzed the ejaculatein 218 cryptorchid men and correlated it with the developmental stage of their germ cells at the time of successful surgery. Results: Abnormal sperm concentration (<40 × 106/ejaculate) was found in half of the patients under the study. 47.5% of unilateral and 78% of bilateral cryptorchid males had their sperm concentration in the infertility range according to the WHO standards. If transformation into Ad spermatogonia had occured, age-related differences in the fertility outcome was observed. The younger the unilateral cryptorchid boys were at surgery, the higher their sperm count. Age-related difference was not found in the group of cryptorchid men having had no A dark spermatogonia at time of surgery, indicating that in this group a successful orchidopexy is insufficient to prevent infertility development and, in particular, the development of azoospermia. Conclusion: The presence of Ad spermatogonia at surgery is an excellent prognostic parameter for future fertility. Cryptorchid boys lacking these cells will develop infertility despite successful orchidopexy at an early age.

This comprehensive review provides in-depth coverage of progress made in understanding the molecular mechanisms underlying cryptorchidism, a frequent pathology first described in about 1786 by John Hunter. The first part focuses on the physiology, embryology, and histology of epididymo-testicular descent. In the last 20 years epididymo-testicular descent has become the victim of schematic drawings with an unjustified rejection of valid histological data. This part also includes discussion on the roles of gonadotropin-releasing hormone, fibroblast growth factors, Müllerian inhibiting substance, androgens, inhibin B, and insulin-like 3 in epididymo-testicular descent. The second part addresses the etiology and histology of cryptorchidism as well as the importance of mini-puberty for normal fertility development. A critical view is presented on current clinical guidelines that recommend early orchidopexy alone as the best possible treatment. Finally, by combining classical physiological information and the output of cutting-edge genomics data into a complete picture the importance of hormonal treatment in preventing cryptorchidism-induced infertility is underscored.

We present a strategy to obtain milligrams of highly post-translationally modified eukaryotic proteins, transiently expressed in mammalian cells as rigid or cleavable fusions with a mammalianized version of bacterial maltose-binding protein (mMBP). This variant was engineered to combine mutations that enhance MBP solubility and affinity purification, as well as provide crystal-packing interactions for increased crystallizability. Using this cell type-independent approach, we could increase the expression of secreted and intracellular human proteins up to 200-fold. By molecular replacement with MBP, we readily determined five novel high-resolution structures of rigid fusions of targets that otherwise defied crystallization.

In a paper from Switzerland, the authors describe the relationship between adult dark spermatogonia and the secretory capacity of Leydig cells in cryptorchidism. OBJECTIVE: To examine whether hormonal therapy before orchidopexy affects the histology of the testis and to assess the responsiveness of the Leydig cells, as it has been shown that although basal plasma testosterone levels are within the ‘normal’ range in cryptorchid boys there is an insufficient increase of testosterone after a human chorionic gonadotrophin (hCG) stimulation in ≈ 30% of cryptorchid boys. PATIENTS AND METHODS: In all, 55 boys (aged 1–7 years) with a unilateral undescended testis were included in the study and divided into two groups. Group I (32 boys) received hormonal therapy before orchidopexy; 17 boys received a long‐acting LHRH analogue (buserelin) administered as a nasal spray in doses of 20 µg/day for 28 days, followed by 1500 IU hCG intramuscularly (i.m.) once a week for 3 weeks, and the remaining 15 received 1500 IU hCG i.m. once a week for 3 weeks. Group II (33 boys) had orchidopexy alone. During orchidopexy biopsies were taken from the undescended and contralateral descended testes of the boys in both groups for histological analyses. Variations in the number of adult dark (Ad) spermatogonia per tubule (Ad/T) were assessed and testosterone levels were measured during the course of the hormonal therapy (before treatment, 14 days after initiation of buserelin administration, 24 h after each hCG injection, and 3 months after cessation of therapy). RESULTS: In group I, 17 boys (53%) had a ‘normal’ Ad/T after hormonal treatment vs only six (18%) in group II after orchidopexy alone ( P = 0.019). In the hormonally treated boys (group I) we compared the testosterone values 24 h after the second injection of hCG (when the response was most pronounced). Those with a normal Ad/T had a mean ( sd ) testosterone level of 199.5 (97.6) ng/dL vs 99.6 (85) ng/dL in those with an inadequate Ad/T response to hormonal therapy ( P < 0.003). CONCLUSION: We have confirmed that there are two subgroups of cryptorchid boys. Patients with a sufficient Leydig cell secretory capacity will have normal testicular histology and Ad spermatogonia count after hormonal treatment. While those with a suboptimal Leydig cell capacity will have a low Ad spermatogonia count and consequently poor prognosis for future fertility, despite successful surgery. As to whether different types and durations of the hormonal therapy in patients with impaired Leydig cell response could lead to improved testicular histology and consequently improved prognosis for future fertility, remains to be answered.

Background: The objective of this study was to compare celiac disease (CD)– specific antibody tests to determine if they could replace jejunal biopsy in patients with a high pretest probability of CD. Methods: This retrospective study included sera from 149 CD patients and 119 controls, all with intestinal biopsy. All samples were analyzed for IgA and IgG antibodies against native gliadin (ngli) and deamidated gliadin peptides (dpgli), as well as for IgA antibodies against tissue transglutaminase and endomysium. Results: Tests for dpgli were superior to ngli for IgG antibody determination: 68% vs. 92% specificity and 79% vs. 85% sensitivity for ngli and dpgli, respectively. Positive (76% vs. 93%) and negative (72% vs. 83%) predictive values were also higher for dpgli than for ngli. Regarding IgA gliadin antibody determination, sensitivity improved from 61% to 78% with dpgli, while specificity and positive predictive value remained at 97% (P < 0.00001). A combination of four tests (IgA anti-dpgli, IgG anti-dpgli, IgA anti- tissue transglutaminase, and IgA anti-endomysium) yielded positive and negative predictive values of 99% and 100%, respectively and a likelihood ratio positive of 86 with a likelihood ratio negative of 0.00. Omitting the endomysium antibody determination still yielded positive and negative predictive values of 99% and 98%, respectively and a likelihood ratio positive of 87 with a likelihood ratio negative of 0.01. Conclusion: Antibody tests for dpgli yielded superior results compared with ngli. A combination of three or four antibody tests including IgA anti-tissue transglutaminase and/or IgA anti- endomysium permitted diagnosis or exclusion of CD without intestinal biopsy in a high proportion of patients (78%). Jejunal biopsy would be necessary in patients with discordant antibody results (22%). With this two-step procedure, only patients with no CD-specific antibodies would be missed.