Effects Of Cryptorchidism Research Articles

Effects of Cryptorchidism on the Semen Quality of Giant Pandas from the Perspective of Seminal Plasma Proteomics

Giant pandas are an endangered species with low reproductive rates. Cryptorchidism, which can negatively affect reproduction, is also often found in pandas. Seminal plasma plays a crucial role in sperm–environment interactions, and its properties are closely linked to conception potential in both natural and assisted reproduction. The research sought to identify seminal fluid protein content variations between normal and cryptorchid giant pandas. Methods: Using a label-free MS-based method, the semen proteomes of one panda with cryptorchidism and three normal pandas were studied, and the identified proteins were compared and functionally analyzed. Results: Mass spectrometry identified 2059 seminal plasma proteins, with 361 differentially expressed proteins (DEPs). Gene ontology (GO) analysis revealed that these DEPs are mainly involved in the phosphate-containing compound metabolic, hydrolase activity, and kinase activity areas (p ≤ 0.05). The KEGG functional enrichment analysis revealed that the top 20 pathways were notably concentrated in the adipocyte lipolysis and insulin metabolism pathway, with a significance level of p ≤ 0.05. Further analysis through a protein–protein interaction (PPI) network identified nine key proteins that may play crucial roles, including D2GXH8 (hexokinase Fragment), D2HSQ6 (protein tyrosine phosphatase), and G1LHZ6 (Calmodulin 2). Conclusions: We suspect that the high abundance of D2HSQ6 in cryptorchid individuals is associated with metabolic pathways, especially the insulin signal pathway, as a typical proteomic feature related to its pathological features. These findings offer insight into the ex situ breeding conditions of this threatened species.

Experimental Cryptorchidism Causes Chronic Inflammation and a Progressive Decline in Sertoli Cell and Leydig Cell Function in the Adult Rat Testis.

Cryptorchidism causes spermatogenic failure and reduced serum androgen levels, as well as testicular oedema and fibrosis, which are hallmarks of inflammation. However, the role of inflammation and the effects of cryptorchidism on Sertoli cell and Leydig cell function at the molecular level remain ill-defined. Bilateral cryptorchidism was surgically induced in adult rats for 7 and 14 weeks. Testis weights decreased to 40% of normal within 7 weeks, due to loss of all developing spermatogenic cells except spermatogonia, but did not decrease further at 14 weeks. Serum FSH and LH were increased at both time points, consistent with a loss of feedback by inhibin and testosterone. This damage was accompanied by progressive accumulation of interstitial fluid and peritubular fibrosis, and a progressive decline of several critical Sertoli cell genes (Sox9, Inha (inhbin α-subunit), Cldn11 (claudin 11), Gja1 (connexin 43), and Il1a (interleukin-1α)) and the Leydig cell steroidogenic enzymes, Cyp11a1, Hsd3b1, and Hs17b3. Activin B and the activin-binding protein, follistatin, also declined, but the intratesticular concentration of activin A, which is a regulator of inflammatory responses, was largely unaffected at either time point. Expression of genes involved in inflammation (Tnf, Il10, Il1b, Mcp1) and fibrosis (Acta2, Col1a1) were considerably elevated at both time points. These data indicate that induction of experimental cryptorchidism, which causes complete failure of spermatogenesis in the adult rat, also induces chronic testicular inflammation, manifesting in oedema and fibrosis, and a progressive decline of Sertoli and Leydig cell gene expression and function.

Role of Epididymis and Testis in Nuclear Factor Erythroid 2-Related Factor 2 Signaling in Mouse Experimental Cryptorchidism

Background: Cryptorchidism is a common gonadal disease in neonates that promotes oxidative stress and reactive oxygen spices production following the presence of testicles in ectopic places. Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling could prevent oxidative stress damage through the Nrf2-driven antioxidants. Objectives: The current study aimed at evaluating the pattern of gene expressions related to this pathway in testis and epididymis of mice experimentally subjected to cryptorchidism. Methods: The current experimental study was conducted on 48 male mice randomly divided into six groups at Arak University of Medical Sciences, Arak, Iran, 2018. Cryptorchidism was induced in the left testis of mice in five experimental groups by removing the testis from the scrotum and suturing it to the muscles of the abdominal wall. One group remained intact as the control group. Sperm parameters were analyzed one day, as well as one, two, four, and eight weeks after the operation. The expression of Nrf2, NQO1, HO1, and Keap1 genes in testis and epididymis was assessed using quantitative reverse transcriptase- polymerase chain reaction. Results: Sperm analysis showed a significant decrease in sperm number, viability, normal morphology (except in the one day group), and motility in all experimental groups compared to the control group (P ≤ 0.05). The expression level of Nrf2 (in testis tissue), Keap1 (in both testis and epididymis), and HO1 (in testis tissue) showed no changes over the time (P > 0.05), while the expression of other genes decreased remarkably (P ≤ 0.05) in both testis tissue and epididymis in a time-dependent manner. Conclusions: The current study findings showed that the expression of genes involved in NRF2 systems decreased in the epididymis of cryptorchid mice more than testis and it suggested that treatment with Nrf2 inducer could decrease destructive effects of cryptorchidism on the reproductive system.

The Regulation of Testicular Descent and the Effects of Cryptorchidism

The first half of this review examines the boundary between endocrinology and embryonic development, with the aim of highlighting the way hormones and signaling systems regulate the complex morphological changes to enable the intra-abdominal fetal testes to reach the scrotum. The genitoinguinal ligament, or gubernaculum, first enlarges to hold the testis near the groin, and then it develops limb-bud-like properties and migrates across the pubic region to reach the scrotum. Recent advances show key roles for insulin-like hormone 3 in the first step, with androgen and the genitofemoral nerve involved in the second step. The mammary line may also be involved in initiating the migration. The key events in early postnatal germ cell development are then reviewed because there is mounting evidence for this to be crucial in preventing infertility and malignancy later in life. We review the recent advances in what is known about the etiology of cryptorchidism and summarize the syndromes where a specific molecular cause has been found. Finally, we cover the recent literature on timing of surgery, the issues around acquired cryptorchidism, and the limited role of hormone therapy. We conclude with some observations about the differences between animal models and baby boys with cryptorchidism.

Plasma insulin-like peptide 3 and testosterone concentrations in male dogs: Changes with age and effects of cryptorchidism

The objectives were to: (1) develop a time-resolved fluorescence immunoassay (TRFIA) to measure insulin-like peptide 3 (INSL3) in canine plasma; (2) investigate changes of plasma concentrations of INSL3 and testosterone with age in normal male dogs; and (3) compare hormonal concentrations among cryptorchid, normal, and castrated dogs to evaluate endocrine function of the Leydig cell component in retained testes. Blood samples were taken from normal male dogs from prepubertal age to advanced age (4 mo to 14 y, n = 89), and from unilateral cryptorchid (n = 31), bilateral cryptorchid (n = 7), and castrated dogs (n = 3). Canine plasma INSL3 was measured with a newly developed TRFIA. The minimum detection limit of the INSL3 assay was 0.02 ng/ml and the detection range was 0.02 to 20 ng/ml. Plasma INSL3 concentrations increased (P < 0.05) from prepubertal age (4–6 mo) to pubertal age (6–12 mo), and then declined (P < 0.05) from pubertal age to post-pubertal age (1–5 y), reaching a plateau. Plasma testosterone concentrations increased (P < 0.0001) dramatically from prepubertal to pubertal ages, and then seemed to plateau. Concentrations of both INSL3 and testosterone were lower (P < 0.0001 for each) in bilateral cryptorchid dogs than in normal and unilateral cryptorchid dogs. The INSL3 (range: 0.05–0.43 ng/ml) and testosterone (range: 0.10–0.94 ng/ml) concentrations were readily detected in bilateral cryptorchids, but not in castrated dogs (INSL3 < 0.02 ng/ml; testosterone < 0.04 ng/ml). In conclusion, plasma INSL3 concentrations in male dogs measured by a newly developed TRFIA had a transient surge at a pubertal age, whereas testosterone did not. Lower plasma concentrations of INSL3 and testosterone in bilateral cryptorchid dogs suggest impaired endocrine functions of Leydig cell component in paired retained testes. Therefore, peripheral plasma INSL3 and testosterone concentrations have potential diagnostic value in predicting the presence of bilaterally retained testes in male dogs.

Subfertility and the risk of testicular germ cell tumors (United States)

Previous studies have reported an association between subfertility and the risk of testicular germ cell tumors. We examined fertility, measured by number of children fathered and prior diagnosis of infertility, as a risk factor for testicular cancer, while accounting for the influence of occult cancer and cryptorchidism. Tumor registry data were used to identify 329 cases of testicular cancer in white men aged 20 to 69 years, diagnosed in western Washington State from 1977 to 1983; 672 cancer-free controls were identified by random-digit dialing. Telephone interviews ascertained reproductive histories and basic demographic information. Logistic regression was used to estimate the relative risk of testicular cancer associated with fertility. Testicular cancer risk was decreased among men who had previously fathered a child (age-adjusted odds ratio (OR) 0.76, 95% confidence interval (CI): 0.54-1.06). Inverse associations were seen for seminomas and non-seminomas, and only slight attenuations in the ORs were observed when men with a history of cryptorchidism were excluded. Prior diagnosis of infertility was associated with an increased risk of testicular cancer (OR 2.40, 95% CI: 1.00-5.77). These results are consistent with an increased risk of testicular cancer among men with reduced fertility that goes beyond the effects of cryptorchidism.

Regulation of Sertoli cell number and activity by follicle-stimulating hormone and androgen during postnatal development in the mouse.

The roles of FSH and androgen in the postnatal development of Sertoli cell number and function have been investigated using mice that lack FSH (FSHbetaKO), FSH-receptors (FSHRKO), or androgen receptors (Tfm). At birth and d 5, Sertoli cell number was normal in FSHRKO and FSHbetaKO mice, but was significantly reduced on d 20 and in adulthood. In contrast, Sertoli cell number was reduced at birth in Tfm mice and remained significantly less than normal up to adulthood. Sertoli cell activity was determined through measurement of 11 different mRNA transcript levels. From birth to adulthood, the expression of most transcripts increased, with a significant rise occurring between d 5 and 10. In animals lacking FSH stimulation, mRNA expression (measured per Sertoli cell) was largely normal on d 5, but was reduced in seven transcripts on d 20 and in five transcripts at adulthood. In Tfm mice two transcripts showed reduced expression on d 5, and four were reduced on d 20, although expression in adult Tfm mice did not differ from that in normal cryptorchid controls. The results show that 1) testosterone, but not FSH, is required for Sertoli cell proliferation during fetal and early neonatal life; 2) FSH and testosterone both regulate the late stages of Sertoli cell proliferation; 3) FSH has a general trophic effect on Sertoli cell activity in the pubertal and adult mouse; and 4) androgens are required for specific transcript expression during prepubertal development. Specific effects of androgens were not seen in the adult, although these may be masked by the effects of cryptorchidism.

Comparison of the effects of vasectomy and experimental cryptorchidism in rats: I. Testicular histology.

The effects of cryptorchidism, one of the most important congenital malformations resulting with the defects in testicular structure thus infertility, is the best known subject in male reproduction. Those best known effects make the usage of cryptorchidism as a second control criteria when the effects of other male infertility reasons are attempted to be determined. Therefore the persistency or reversibility of the effects of vasectomy on testicular structure have been compared to the testicular features following experimental cryptorchidism and to the control group findings. To do this, rats were divided into 3 groups. While the control group animals were sham operated, the experimental group animals were undergone either vasectomy or experimental cryptorchidism procedures. Testicular histology of the control and experimental groups was determined using convenient staining methods at the light microscopical level. The comparison of the findings from the control and experimental groups showed that the testicular features of the vasectomized group were similar to those seen in the control group in contrast to the experimental cryptorchidism group which had irreversible testicular alterations. Results of the present study indicated the convenience of the usage of vasectomy in male contraception.

Down-Regulation of Steroidogenic Cytochrome P450XVII in Cryptorchid Rat Testes

The objective of the present study was to investigate the regulation of a key component of testicular androgen biosynthesis, i.e. the cytochrome P450XVII of the steroid-17 alpha-monooxygenase/C17,20-lyase, after surgical induction of bilateral cryptorchidism in vivo. Seven days after induction of cryptorchidism, P450XVII concentrations are diminished (as compared to sham-operated controls) by 64% in isolated purified Leydig cells but only by 44% in the total Leydig cell compartment of the testis, since the Leydig cell yield from cryptorchid testes is by 53% higher than that from control testes. Using microsomal suspensions prepared from testicular homogenates, P450XVII content per testis equivalent is found to be decreased by 36% seven days after incubation of cryptorchidism, whereas the P450XVII concentration per gram testis is not changed due to testicular involution. Fourteen days after induction of cryptorchidism, the induction of the Leydig cell system appears to superimpose on the down-regulation of P450XVII. The study demonstrates both a strong sensitivity of P450XVII to short-term elevation of testicular temperature and a differentiation between effects of cryptorchidism on total testicular content and specific cellular and subcellular concentration of this steroidogenic protein.

Cellular distribution, developmental changes and effects of cryptorchidism on uridine kinase in the rat testis.

High specific activity of uridine kinase was found in cultured peritubular cells (3.0 nmol/min per mg protein) which was more than 3-fold higher than that found in cultured Sertoli cells (0.79 nmol/min per mg protein). In the various classes of germ cells a decrease in specific uridine kinase activity was associated with increased maturity of the cells, primary spermatocytes, round spermatids and spermatozoa showing 1.3, 0.65 and 0.16 nmol/min per mg protein, respectively. A relationship between uridine kinase activity and the rate of RNA synthesis in these cells is suggested. A decrease in specific uridine kinase activity in testis with increasing age supports the finding of lower uridine kinase in mature germ cells than in earlier germ cells and somatic cells. This finding is further supported by the observation that cryptorchidism, which is associated with a time-dependent depletion of germ cells, resulted in an increase in specific uridine kinase activity. The results indicate that pyrimidine salvage is important in earlier germ cells, as well as in somatic cells in the testis, to produce substrates for nucleic acid synthesis.

Effects of cryptorchidism and orchidopexy on deoxyribonucleoside-activated nucleotidase (DAN) in the rat testis

1. 1. Unilateral cryptorchidism was associated with an increase in specific DAN activity in the abdominal testis of adult rats. 2. 2. In the scrotal, immature testis, there was an age-dependent decrease in specific DAN activity similar to that normally seen in rats. This decrease was less pronounced in the abdominal testis of unilaterally cryptorchid rats. 3. 3. Total DAN activity in the abdominal testis showed a decrease in both immature and adult rats, when compared to that of the scrotal testis. 4. 4. Orchidopexy following cryptorchidism in adult rats, resulted in complete restoration of DAN activity in spite of poor recovery of spermatogenesis.

Undescended Testis: The Effect of Treatment on Subsequent Risk of Subfertility and Malignancy

The literature was reviewed for information on the long-term effects of cryptorchidism on fertility and cancer incidence. In unilateral cryptorchidism, treatment policies of orchidopexy alone, or of human chorionic gonadotrophin (hCG) therapy followed, if necessary, by orchidopexy, have resulted in similar levels of reduced fertility (15% azoospermia, and an additional 30% oligospermia, ie, sperm count less than 20×10 6 /mL). Very similar results were observed in unilateral cryptorchid men who had had no treatment (and were still cryptorchid at semen examination). In contrast, no untreated bilaterally cryptorchid men have normal fertility (sperm count greater than 20×10 6 /mL), whereas of those treated, a quarter have normal fertility. In some series, as many as half of the bilateral cryptorchid testes descended following hormonal treatment; a finding that could be attributed, at least in part, to the frequent difficulty in deciding on clinical examination, whether these testes are truly cryptorchid. There is little evidence that operation early rather than late within the age range of 4 to 14 years has any effect on subsequent fertility. Histologic studies suggest that orchidopexy should be carried out before age 2, but there are almost no follow-up data with which to evaluate the results of early operation. Since there is evidence that orchidopexy may result in testicular atrophy in a small proportion of cases, a trial of luteinizing hormone-releasing hormone (LHRH) may be advisable. There is little information available concerning the effect of age at orchidopexy on the subsequent risk of testicular cancer. Testes that cannot be brought into the scrotum should be excised.

Differential effects of cryptorchidism and short photoperiod on testicular prolactin and LH/human chorionic gonadotrophin receptors in the golden hamster.

Gonadal atrophy induced by short photoperiods in male golden hamsters is accompanied by a decrease in the total content of testicular prolactin and LH/human chorionic gonadotrophin (LH/hCG) receptors and a concomitant rise in the concentrations of LH receptors. Atrophic testes are typically abdominal. In this study, we have compared the effects of experimentally induced cryptorchidism and the effects of a short photoperiod on testicular prolactin and LH/hCG receptors. Cryptorchidism produced the expected decrease in testicular weight and an increase in plasma FSH concentrations, without altering plasma concentrations of LH or prolactin and with a relatively small decrease in plasma testosterone. It also produced an increase in the concentration of prolactin and LH/hCG receptors without significant changes in their total content. Exposure to a short photoperiod decreased weights of testes and seminal vesicles and plasma levels of prolactin and testosterone, with no significant effects on plasma gonadotrophin levels. Short photoperiod also increased the concentration of LH/hCG receptors but, in contrast to the effects of cryptorchidism, it produced a precipitous decline in the total content of testicular receptors for both prolactin and LH/hCG. We conclude that changes in prolactin and hCG binding measured in membrane preparations from decapsulated testes of hamsters exposed to a short photoperiod cannot be explained by the abdominal position of the gonads, abnormalities of Sertoli cell function or changes in the relative proportion of Leydig cells in the atrophic testes.

Effect of cryptorchidism and orchidopexy on inhibin secretion by rat Sertoli cells.

The present study explored the effects of experimental bilateral cryptorchidism (of 21-, 28-, and 35-days duration) and orchidopexy (14 and 42 days) in the adult rat on the secretion of inhibin by cultures of isolated Sertoli cells. Changes in serum levels of gonadotropins, testis weight, and spermatogenesis also were assessed to verify the effectiveness of the surgical procedures. Cryptorchidy resulted in a progressive decline in testicular weight and a loss of germ cells, associated with increasing serum levels of FSH and LH. Inhibin secretion in vitro became nondetectable by 28 days after surgery. At 42 days after orchidopexy, spermatogenesis showed qualitative recovery, with a small increase in testes weight. Levels of LH in the circulation declined, but only to twice the intact control levels. However, inhibin secretion and serum FSH levels returned to nearly normal values. These results indicate that bilateral cryptorchidism severely impairs the secretion of inhibin and possibly other Sertoli cell functions which may account, at least partly, for the increase in circulating FSH levels and the arrest of spermatogenesis. The effects of cryptorchidism on these parameters can be reversed to a large degree by orchidopexy.