Prostaglandins signaling molecules are involved in numerous physiological processes. They are produced by several enzyme-limited reactions upon fatty acids, which are catalyzed by two cyclooxygenases and prostaglandin synthases. In particular, the prostaglandins E2 (PGE2), D2 (PGD2), and F2 (PGF2 α) have been shown to be involved in female reproductive mechanisms. Furthermore, widespread expression of lipocalin- and hematopoietic-PGD2 synthases in the male reproductive tract supports the purported roles of PGD2 in the development of both embryonic and adult testes, sperm maturation, and spermatogenesis. In this review, we summarize the putative roles of PGD2 signaling and the roles of both PGD2 synthases in testicular formation and function. We review the data reporting the involvement of PGD2 signaling in the differentiation of Sertoli and germ cells of the embryonic testis. Furthermore, we discuss the roles of lipocalin-PGD2 synthase in steroidogenesis and spermatogenesis, in terms of lipid molecule transport and PGD2 production. Finally, we discuss the hypothesis that PGD2 signaling may be affected in certain reproductive diseases, such as infertility, cryptorchidism, and testicular cancer.
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- Abstract: testicle x
- Abstract: leydig x
- Abstract: sertoli x
- Abstract: epididymis x
- Abstract: testes x
- Abstract: seminiferous tubules x
- Abstract: blood-testes barrier x
- Abstract: interstitial x
- Abstract: spermatogenesis x
- Abstract: rete testis x
- Abstract: vas deferens x
- Abstract: cryptorchidism x
Moïra Rossitto, Safdar Ujjan, Francis Poulat and Brigitte Boizet-Bonhoure
T. D. GLOVER
(I) Fourteen adult male rabbits have been subjected to unilateral isolation of the tail of the epididymis in the abdomen, with subsequent retention of the organ in an abdominal position. Isolation of the contralateral cauda epididymidis in each rabbit was effected in the scrotum as a control measure. (2) Estimates of the proportion of dead and decapitated spermatozoa as well as the incidence of spermatozoa with coiled tails, at different levels of the tubule distal to the point of isolation, have demonstrated a delayed response of so-called mature spermatozoa to the conditions of experimental cryptorchidism. (3) Quantitative assessments of these criteria have suggested that spermatozoa in the body of the epididymis are more susceptible to degeneration than those in the tail of the epididymis, but it is pointed out that more evidence is yet required on this matter. (4) The overall results are discussed in relation to previous work concerning the origin of similar sperm abnormalities.
Cl. JEAN, M. ANDRÉ, Ch. JEAN, M. BERGER, M. DE TURCKHEIM and G. VEYSSIÈRE
The injection of pregnant mice with 5 mg oestradiol dipropionate induced a high proportion of bilateral cryptorchidism in the male offspring. The ectopic testes were reduced in size and occupied one of three different positions in the abdomen: pararenal, paravesicular or inguinal. The seminal vesicles were found to be similarly reduced in size whereas the adrenals and pituitaries appeared to be unaffected. The total content of testosterone was reduced in the pararenally placed gonads but was not significantly different from that of the controls when the testes were in the inguinal region. The content of androstenedione was not significantly altered. The concentration of both hormones, however, was increased in all cases. Plasma testosterone levels were lower in all the offspring of treated mothers, especially in those with high ectopia.
H. Ikadai, C. Ajisawa, K. Taya and T. Imamichi
Summary. A new rat line (TS inbred rats) showing uni- or bilateral ectopic scrota in about 70% of the males was established. Ectopic scrota were elongated pouches of the thin muscle layer under the suprainguinal body skin, in which hypoplastic testes and epididymides were seen. Genetic analysis revealed that the ectopic scrotum was controlled by multiple genes. Groups of 5 normal, uni- and bilaterally affected rats were killed at 25 weeks of age. Histologically, ectopic testes of uni- and bilaterally affected rats showed arrest of spermatogenesis at the primary spermatocyte stage. Contralateral testes of unilaterally affected rats were normally descended and showed normal spermatogenesis. No abnormality was seen in the urinary system. Plasma concentrations of FSH were significantly elevated in bilaterally affected rats but plasma concentrations of testosterone and LH were unchanged in uni- and bilaterally affected rats. Pituitary contents of LH and FSH were significantly elevated in bilaterally affected rats. The endocrinological status of TS inbred rats was therefore similar to that of experimentally induced cryptorchid rats.
Keywords: ectopic scrotum; inheritance; rat; testis; LH; FSH; testosterone
Fernando F Migone, Pei-hsuan Hung, Robert G Cowan, Vimal Selvaraj, Susan S Suarez and Susan M Quirk
The influence of the hedgehog signaling pathway on reproduction was studied in transgenic mice in which a dominant active allele of the hedgehog signal transducer, smoothened (Smo), was conditionally expressed in the developing Müllerian duct and gonads through recombination mediated by anti-Müllerian hormone receptor 2-cre (Amhr2 cre). Previous studies showed that development of the oviduct and uterus are abnormal in female Amhr2 cre/+ SmoM2 mice. In the current study, focusing on mutant males, litter size was reduced 53% in crosses with wild-type females. An extra band of undifferentiated tissue extended along each epididymis and vas deferens, a position suggesting derivation from Müllerian ducts that failed to regress fully. Hedgehog signaling was elevated in this tissue, based on mRNA levels of target genes. Amhr2 mRNA was dramatically reduced in the uterus of mutant females and in the extra tissue in the tract of mutant males, suggesting that AMHR2 signaling was inadequate for complete Müllerian duct regression. Spermatogenesis and sperm motility were normal, but testis weight was reduced 37% and epididymal sperm number was reduced 36%. The number of sperm recovered from the uteri of wild-type females after mating with mutant males was reduced 78%. This suggested that sperm transport through the male tract was reduced, resulting in fewer sperm in the ejaculate. Consistent with this, mutant males had unusually tortuous vas deferentia with constrictions within the lumen. We concluded that persistence of a relatively undifferentiated remnant of Müllerian tissue is sufficient to cause subtle changes in the male reproductive tract that reduce fertility.
J. L. FLEEGER, J. P. BISHOP, W. R. GOMES and N. L. VanDEMARK
Experiments were conducted using twenty-four mature male rabbits to determine the effects of short-term unilateral cryptorchidism on the fatty acid composition of testicular phospholipids and triglycerides.
Total lipids were extracted from testes from unoperated control rabbits and from rabbits rendered unilaterally cryptorchid for 2, 4 or 6 days. Phospholipids and triglycerides were separated by thin layer chromatography. The methyl esters of the fatty acids in each fraction were separated and measured using gas-liquid chromatography.
The phospholipid fraction was relatively high in the fatty acids palmitate, stearate and oleate whereas the triglyceride fraction contained relatively high levels of oleate, linoleate and palmitate. In the phospholipid fraction of the translocated testes, the proportion of palmitate rose after 2 days (P<0·01), returned to control levels at 4 days, then decreased (P<0·01) 6 days after translocation. Stearate, palmitaldehyde and stearaldehyde concentrations increased (P<0·001) in translocated testes at 4 and 6 days. Concentration of oleate in the phospholipid fraction decreased (P<0·01) after 2 or 4 days and linoleate was lower (P<0·05) than controls after 2 and 6 days of translocation. In the phospholipid fraction of scrotal testes, palmitate percentage increased (P<0·05) at 2 days, and linoleate and stearate decreased (P<0·05) at 2 and 6 days, respectively.
Palmitate concentration in the triglyceride fraction of translocated testes increased (P<0·05) at 2 and 6 days as did stearate percentage (P<0·01) after 6 days. Myristate was also higher after 4 days of translocation (P<0·05). A decreased percentage of oleate was found in the triglyceride fraction of 4- and 6-day translocated testes. Triglycerides from the scrotal testes contained higher levels of palmitoleate (P<0·05) and myristate (P<0·05) than unoperated controls, but lesser percentages of stearate (P<0·01).
Juan P Arrebola, José M Molina-Molina, Mariana F Fernández, Jose M Sáenz, Esperanza Amaya, Paolo Indiveri, Elizabeth M Hill, Martin Scholze, Frances Orton, Andreas Kortenkamp and Nicolás Olea
It has been hypothesized that the rise in male reproductive disorders over recent decades may at least be partially attributable to environmental factors, including chemical exposures, but observed associations with single chemicals were rather weak. The aim of this case–control study was to explore the relationship between exposure to mixtures of (anti-)androgenic chemicals during pregnancy and the risk of cryptorchidism and/or hypospadias in offspring, using the total effective xenobiotic burden of anti-androgens (TEXB-AA) as a biomarker. A subsample of 29 cases (16 of cryptorchidism, 12 of hypospadias, and one of both disorders) and 60 healthy controls was nested in a cohort of male newborns recruited between October 2000 and July 2002. The (anti-)androgenic activity of placenta samples collected at delivery was assessed using TEXB-AA biomarker, combined with a bioassay-directed fractionation protocol that separated endogenous hormones from most (anti-)androgenic chemicals by normal-phase HPLC. The bioassay measures the androgen-induced luciferase activity and the inhibition of this pathway by (anti-)androgens. First, we collected 27 HPLC fractions in each placenta extract, which were all tested in the bioassay. The multivariable statistical analyses indicated a statistically significant positive dose–response association between the potent anti-androgenic activity of the HPLC fraction collected during minutes 1–2 (F2) and the risk of malformations (odds ratio: 2.33, 95% CI: 1.04–5.23). This study represents a novel approach for the estimation of combined effects of the total anti-androgenic load and the associations suggest an effect of environmental pollutants on the development of fetal reproductive tract.
Free Spanish abstract: A Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/149/6/605/suppl/DC1.
EJ Peirce and WG Breed
The plains rat, Pseudomys australis, and the spinifex hopping mouse, Notomys alexis, show marked differences in the size of their testes and in the number of spermatozoa within the epididymides. In the present study, the dynamics of sperm production and the duration of sperm transit along the male excurrent ducts were compared between these two species. The durations of the cycle of the seminiferous epithelium, spermatogenesis and sperm transit were determined by tracking cells using autoradiography after [(3)H]thymidine incorporation. Daily sperm production was determined from counts of testicular spermatids after homogenization and further estimates of sperm transit were obtained by dividing sperm reserves within the various regions of the extratesticular ducts by the daily sperm production of the attached testis. In the plains rat, the mean duration of the cycle of the seminiferous epithelium was 11.2 days, the duration of spermatogenesis was 45 days, daily sperm production was 2.6 x 10(7) spermatozoa per gram of testis and epididymal transit of spermatozoa took approximately 9 days (caput 0.8 days; corpus 1.5 days; cauda 6.5 days). In contrast, in the hopping mouse, the mean duration of the cycle of the seminiferous epithelium was 14 days, the duration of spermatogenesis was 56 days and daily sperm production per gram of testis was < 1.0 x 10(7). Epididymal transit of spermatozoa was completed in about 4 days (caput + corpus < 1 day; cauda 3 days); however, spermatozoa may be stored for an additional 1.5-2.0 days in the vas deferens. These results indicate that, in addition to small testes, the hopping mouse shows a low efficiency of sperm production, a relatively long duration of spermatogenesis and rapid passage of spermatozoa through the epididymis, all of which contribute to low epididymal sperm counts. These data are considered in relation to interspecific differences in sperm competition.
T. D. GLOVER
A comparison of certain features of the testis and epididymis has been made in five species of East African mammals, two of which, the rock hyrax and elephant, have abdominally situated testes.
The artery to the testes was straight in the species with abdominally situated testes and there was no pampiniform plexus while in the species with scrotal testes, it was coiled in the region of the plexus. It is suggested that where the testicular artery is coiled, the testes should be regarded as basically scrotal, even if they are usually found in the abdomen post mortem.
A striking increase in blood flow in the testis of the rock hyrax during sexual activity suggests that the simpler arterial pattern of the testis in testicond mammals allows a greater variation in blood flow than the more complicated arterial design associated with scrotal testes.
Characteristic signs of sperm maturation occur in the epididymis of testicond mammals in contrast to the situation in artificial cryptorchidism, where normal epididymal function is completely disrupted. It is suggested that epididymal function, as well as spermatogenesis, has become modified during evolution. Evidence is given that a need for prolonged survival of spermatozoa in the mesonephric duct might have been an important primary factor in the caudal migration of gonads into a scrotum.
Joanne Doran, Cara Walters, Victoria Kyle, Peter Wooding, Rebecca Hammett-Burke and William Henry Colledge
The Mfsd14a gene, previously called Hiat1, encodes a transmembrane protein of unknown function with homology to the solute carrier protein family. To study the function of the MFSD14A protein, mutant mice (Mus musculus, strain 129S6Sv/Ev) were generated with the Mfsd14a gene disrupted with a LacZ reporter gene. Homozygous mutant mice are viable and healthy, but males are sterile due to a 100-fold reduction in the number of spermatozoa in the vas deferens. Male mice have adequate levels of testosterone and show normal copulatory behaviour. The few spermatozoa that are formed show rounded head defects similar to those found in humans with globozoospermia. Spermatogenesis proceeds normally up to the round spermatid stage, but the subsequent structural changes associated with spermiogenesis are severely disrupted with failure of acrosome formation, sperm head condensation and mitochondrial localization to the mid-piece of the sperm. Staining for β-galactosidase activity as a surrogate for Mfsd14a expression indicates expression in Sertoli cells, suggesting that MFSD14A may transport a solute from the bloodstream that is required for spermiogenesis.