Academic literature on the topic 'Testicular descent, cryptorchidism, descent disorders, testes'

Relevance. Male fertility is largely dependent on the timely testicular descent into the scrotum and the formation of the two major divisions of the testis: interstitial and seminiferous tubules. The purpose of research - to reveal ultrastructural changes in the germinal epithelium of the testes with cryptorchidism and assess their degree of severity of patients of different age. Materials and methods. To study the ultrastructure of testis in 30 children with inguinal retention testicular biopsy runtime relegated gonads were done. Before surgery clinically and sonographically determined testicle in the groin area. Children age 1 to 14 years. All the children with unilateral cryptorchidism. In the study of testicular tissue ultrastructural changes in cryptorchidism revealed 3 types of state tubules and germinal epithelium. Changes in type I revealed 4 cases (13%). In type II tubules in the testis revealed mixed cell type: along with light cells therein are determined cells with dark cytoplasm and signs of destruction - 13 boys (46.4%). In 11 (37%) boys identified type III tubules dominated cells with signs of degradation. Conclusions. The study revealed destructive changes of the germinal epithelium of the seminiferous tubules with cryptorchidism: vacuolization of cytoplasm, cytoplasmic foci of local degradation of the matrix, swelling of mitochondria, cristae destruction and devastation of the mitochondrial matrix, pycnosis cores and peritubular interstitial testicular sclerosis, signs of microcirculation disorders.

Abstract STUDY QUESTION Are maternal serum phthalate metabolite, phenol and paraben concentrations measured at 10–17 weeks of gestation associated with male infant genital developmental outcomes, specifically cryptorchidism, anogenital distance (AGD), penile length and testicular descent distance, at birth and postnatally? SUMMARY ANSWER Maternal serum bisphenol A (BPA) concentration at 10–17 weeks of gestation was positively associated with congenital or postnatally acquired cryptorchidism, and n-propyl paraben (n-PrP) concentration was associated with shorter AGD from birth to 24 months of age. WHAT IS KNOWN ALREADY Male reproductive disorders are increasing in prevalence, which may reflect environmental influences on foetal testicular development. Animal studies have implicated phthalates, BPA and parabens, to which humans are ubiquitously exposed. However, epidemiological studies have generated conflicting results and have often been limited by small sample size and/or measurement of chemical exposures outside the most relevant developmental window. STUDY DESIGN, SIZE, DURATION Case–control study of cryptorchidism nested within a prospective cohort study (Cambridge Baby Growth Study), with recruitment of pregnant women at 10–17 postmenstrual weeks of gestation from a single UK maternity unit between 2001 and 2009 and 24 months of infant follow-up. Of 2229 recruited women, 1640 continued with the infancy study after delivery, of whom 330 mothers of 334 male infants (30 with congenital cryptorchidism, 25 with postnatally acquired cryptorchidism and 279 unmatched controls) were included in the present analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS Maternal blood was collected at enrolment, and serum levels of 16 phthalate metabolites, 9 phenols (including BPA) and 6 parabens were measured using liquid chromatography/tandem mass spectrometry. Logistic regression was used to model the association of cryptorchidism with serum chemical concentrations, adjusting for putative confounders. Additionally, offspring AGD, penile length and testicular descent distance were assessed at 0, 3, 12, 18 and 24 months of age, and age-specific Z scores were calculated. Associations between serum chemical levels and these outcomes were tested using linear mixed models. MAIN RESULTS AND THE ROLE OF CHANCE Maternal serum BPA concentration was associated with offspring all-type cryptorchidism both when considered as a continuous exposure (adjusted odds ratio per log10 μg/l: 2.90, 95% CI 1.31–6.43, P = 0.009) and as quartiles (phet = 0.002). Detection of n-PrP in maternal serum was associated with shorter AGD (by 0.242 standard deviations, 95% CI 0.051–0.433, P = 0.01) from birth to 24 months of age; this reduction was independent of body size and other putative confounders. We did not find any consistent associations with offspring outcomes for the other phenols, parabens, and phthalate metabolites measured. LIMITATIONS, REASONS FOR CAUTION We cannot discount confounding by other demographic factors or endocrine-disrupting chemicals. There may have been misclassification of chemical exposure due to use of single serum measurements. The cohort was not fully representative of pregnant women in the UK, particularly in terms of smoking prevalence and maternal ethnicity. WIDER IMPLICATIONS OF THE FINDINGS Our observational findings support experimental evidence that intrauterine exposure to BPA and n-PrP during early gestation may adversely affect male reproductive development. More evidence is required before specific public health recommendations can be made. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a European Union Framework V programme, the World Cancer Research Fund International, the Medical Research Council (UK), Newlife the Charity for Disabled Children, the Mothercare Group Foundation, Mead Johnson Nutrition and the National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre. Visiting Fellowship (J.M.): Regional Programme ‘Jiménez de la Espada’ for Research Mobility, Cooperation and Internationalization, Seneca Foundation—Science and Technology Agency for the Region of Murcia (No. 20136/EE/17). K.O. is supported by the Medical Research Council (UK) (Unit Programme number: MC_UU_12015/2). The authors declare no conflict of interest.

BackgroundCryptorchidism or failure of testicular descent is the most common genitourinary birth defect in males. While both the insulin-like peptide 3 (INSL3) and its receptor, relaxin family peptide receptor 2 (RXFP2), have been demonstrated to control testicular descent in mice, their link to human cryptorchidism is weak, with no clear cause–effect demonstrated.ObjectiveTo identify the genetic cause of a case of familial cryptorchidism.MethodsWe recruited a family in which four boys had isolated bilateral cryptorchidism. A fourth-degree consanguineous union in the family was reported. Whole exome sequencing was carried out for the four affected boys and their parents, and variants that segregated with the disorder and had a link to testis development/descent were analysed. Functional analysis of a RXFP2 variant in cell culture included receptor localisation, ligand binding and cyclic AMP (cAMP) pathway activation.ResultsGenomic analysis revealed a homozygous missense variant in the RXFP2 gene (c.1496G>A .p.Gly499Glu) in all four affected boys and heterozygous in both parents. No other variant with a link to testis biology was found. The RXFP2 variant is rare in genomic databases and predicted to be damaging. It has not been previously reported. Functional analysis demonstrated that the variant protein had poor cell surface expression and failed to bind INSL3 or respond to the ligand with cAMP signalling.ConclusionThis is the first reported genomic analysis of a family with multiple individuals affected with cryptorchidism. It demonstrates that recessive variants in the RXFP2 gene underlie familial cryptorchidism and solidifies the link between this gene and testicular descent in humans.

Cryptorchidism is a condition in which one or both testes have not passed down into the scrotal sac. It is categorized as true undescended testis in which testes are present in the normal path of descent, and as ectopic testis, in which testes are present at abnormal site. Common complications of cryptorchidism are testicular torsion, subfertility, inguinal hernia, and testicular cancer. Here we present a rare case of pantaloon hernia of obstructed indirect component and direct component with cryptorchidism.

In the embryonic stage, the testes develop in the abdomen and descend to scrotum, just before or at birth. The undescended testis is the result of the arrest of descent of testis in some part along its path, to the scrotum. The bilateral undescended testis is called Cryptorchidism which means hidden testis. The factors that contribute to the descent of testis includes Gubernaculum testis, the differential growth of abdominal wall, intra-abdominal pressure and temperature, Calcitonin gene-related peptide (CGRP), male sex hormones, insulin-like hormone 3 (INSL3) and maternal gonadotrophins. The descent of testis may become erratic and gives rise to undescended testis, ectopic testis, congenital hernia, and hydrocoele etc. As a rough estimate approximately 2-4% of male infants are born with Cryptorchism, thus making it, one of the most common congenital anomalies, in the male genitalia. It was found that the incidence of azoospermia in unilateral cryptorchidism was 13%, but in untreated bilateral cryptorchidism, it reaches up to 89%. Cryptorchid boys have increased the risk of a testicular tumor, mainly seminoma. Persistent exposure to high temperature in cryptorchidism could allow maturation of the neonatal gonocytes that has failed to mature as spermatogonia or undergo apoptosis. These cells may persist in testes for years together and eventually become carcinoma in situ cells with a high risk of testicular malignancy later in life i.e., 20-40 years of age. This review addresses the cryptorchidism, its influence on fertility and the risk of developing testicular germ cell tumor. The hormonal factors involved in testicular descend or otherwise is also highlighted.

Abstract Objectives To study the effect of combined gonadotropin therapy (CGT) on testicular descent ± spermatogenesis in congenital hypogonadotropic hypogonadism (CHH) patients with cryptorchidism beyond infancy. Methods This retrospective cohort study included CHH patients with cryptorchidism [bilateral (n=5) or unilateral (n=1)] treated with CGT for testicular descent ± pubertal induction. All participants were treated with CGT [human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG)] with hMG pretreatment in three and monitored for changes in testicular volume (TV), serum total testosterone (T), serum inhibin-B, and sperm concentration. Results Complete testicular descent to the scrotal position was achieved in 5/6 patients (10/11 testes) after 4.7 ± 1.6 months of treatment. There was 44 ± 18%, 97.5% (IQR: 44–195), 10-fold (IQR: 3–19.6), and two-fold (IQR: 1.7–9.3) increase in stretched penile length, ultrasound measured TV, T level, and serum inhibin-B from baseline, respectively. In two pediatric cases, testicular descent occurred with isolated hMG therapy. At the last follow up (median: 23.5, IQR: 10.5–38.7 months), all the descended testes remained in scrotal position. In four pubertal/postpubertal age patients, continuous CGT (18–60 months) yielded T and inhibin-B levels of 16.64 ± 1.46 nmol/l and 106 ± 32.6 pg/mL, respectively. All the three patients with available semen analysis had sperm concentration of ≥5 million/mL and one of them achieved paternity. Conclusions A trial of CGT before orchiopexy may be considered in CHH males with cryptorchidism even beyond the narrow age-window of infancy. CGT may also have beneficial effects on future spermatogenesis and fertility outcomes in these patients.

Abstract 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.

Introduction The term cryptorchidism originates from the Greek kryptos (concealed) and orchis (testis). The definition of the term cryptorchidism is appropriate; not only is the testis concealed, but so is much information regarding this common condition. More than 200 years ago, John Hunter described descent of the testis during the last 3 months of gestation and reported that testes that remain in the abdomen are unhealthy and do not function well. He also discussed the possibilities of failure to descend causing testicular abnormality and testicular abnormalities causing failure to descend. Cryptorchidism represents the most common genital abnormality seen by pediatric urologists. The incidence is 1 in 125 boys. The incidence is much higher in premature infants (1 in 3), and the lower the birth weight, the greater the incidence of cryptorchidism. This condition is seen in approximately 1 in 30 full-term infants, but in many of them, the testicles will descend during the first few months of life. There is a higher incidence of cryptorchidism associated with many chromosomal and single gene defects as well as with multiple malformation syndromes. In addition, there is a higher incidence of cryptorchidism in the siblings and sons of those who have or had cryptorchidism. We will describe the anatomy of both the cryptorchid and retractile testis and discuss the embryology of testicular descent, with an emphasis on hormonal factors.

Background: Cryptorchidism or undescended testis is an evolutionary defect where one or both testes fail to descend into the scrotum. HCG causes the testes to fail, possibly due to weight gain, an increase in testicular vasculature, and stimulating the testosterone and di-hydro-testosterone. The present study has been conducted to evaluate the therapeutic effects of HCG on patients with unilateral cryptorchidism. Methods: In a prospective descriptive study, 211 patients of 8 months to 7 years old with unilateral cryptorchidism whose parents refused surgery received HCG therapy. The patients were followed up 1 month, 3months, and 12 months after the first injection. They were examined in terms of the location of testes, possible relapses, sides of undescended testes, treatment complications, and HCG therapeutic results. Results: Four weeks after the first injection, 160 patients (75.12%) out of 211 cases had the descent of testes into the inguinal canal and the scrotum. 69.5% of non-palpable abdominal testes descended into the inguinal canal, 69.7% of patients with inguinal testes, 78% of patients with supra inguinal testes and 100% of patients with retractile testis experienced the descent of testes into the scrotum. Conclusion: The therapeutic response to HCG was successful in more than 50% of the cases in all the groups. Therefore, the need for performing surgical procedures on children with unilateral cryptorchidism would be decreased and they can be treated by a cost-effective and less invasive method. Moreover, at least one-year follow-up of the patients is required to ensure outcomes of the treatment.

Abstract Background and aims: Undescended testes or Cryptorchidism is a common congenital anomaly of male gonad. In this condition one or both testes fail to descend into the scrotum as the process of descent may get arrested at any point along its normal path. It is a common condition occurring in 1 in 500 individuals. Undescended testis carries a risk of developing seminoma and is prone to injury. Undescended testis also fails to produce mature spermatozoa leading to infertility. Materials and methods: Hundred perinatal human cadavers were collected and meticulously dissected. Results: Undescended testes were found in 30% cases. In 50% cases, left testis descended earlier than the right. Bilateral undescended testes (70%) were more common than unilateral (30%). Unilateral undescended testis was more common on right side (55.5%). Undescended testes were found in the abdomen in 19.61% of cases. In 50.98% of cases, they were located in the ingoina1region and in the remaining 29.41% of cases, they were found in the subinguinal position. Conclusion : The primary management of cryptorchidism is surgery which is called orchipexy and is usually performed in infancy. When the undescended testis is in the inguinal canal, hormone therapy is sometimes attempted and occasionally successful. Therefore through early diagnosis and surgical interventions, the undescended testes can be replaced to the scrotum that will ensure optimal fertility in adulthood and a considerable lessened risk of testicular carcinoma.

This chapter describes the causes, symptoms and clinical management strategies of three disorders affecting the testes; anorchia (both congenital and acquired), testicular maldescent, and varicocele. Absence of both testes in baby boys (bilateral congenital anorchia) is infrequent. Unilateral anorchia or monorchidism is more common. Vascular accidents in gestation appear to be the major cause of anorchia. Bilateral anorchia is associated with changes in luteinizing hormone, follicle-stimulating hormone, and testosterone levels. Once the diagnosis of bilateral anorchia is made, both sterility and the requirement for androgen replacement therapy need to be considered. For treatment, androgen replacement therapy induces pubertal virilization and maintains it in adult life. Torsion and orchidectomy or failed orchiopexy for maldescent are the commonest causes of acquired anorchia. Clinical evaluation and androgen replacement therapy for acquired anorchia are as for congenital anorchia. Normal testes may not complete descent into the scrotum until after birth, particularly in premature infants. The pathological condition of testicular maldescent generally includes incompletely descended or ectopic testes. Infertility is an important problem in patients with a past history of maldescended testes, though whilst the causes of maldescended testes may be multifactorial, the majority of infertile patients with maldescended testes have no other relevant clinical features. Clinical guidelines for treatment of maldescended testes recommend orchiopexy for congenital forms between 6 and 12 months of age, and as soon as possible for those discovered later and for acquired maldescent. Varicocele is one of the most enigmatic and controversial areas in reproductive medicine; a dilation of the pampiniform plexus that usually affects the left side. Its pathogenesis, effects on the testis and, particularly, the benefits of treatment for infertility remain uncertain. Some adults with varicoceles complain of testicular discomfort, a feeling of weight or a dragging sensation in the scrotum. However, many men with a varicocele are unaware of its presence. The mechanism of development of the common varicocele is regarded as a missing or incompetent valve, although they can also result from portal hypertension or intra-abdominal venous obstruction. Asymmetrical testicular size is a frequent accompaniment to the presence of a varicocele, and on average poorer semen quality is present in affected men. They are most easily detected with the man standing upright. Inspection of the scrotum shows an enlargement of the left side of the scrotum, and the dilated veins maybe apparent. Most treatments involve venographic or surgical obstruction of the incompetent veins, though a variety of surgeries have also been performed. The association between varicoceles and infertility is controversial and a Cochrane Review concluded that there is insufficient evidence to support varicocele treatment for infertility. However, the field remains confused and contradictory.

Sexual differentiation is a sequential process that begins at fertilization with the establishment of chromosomal sex, continues with the determination of gonadal sex, and culminates in the development of secondary sexual characteristics that comprise the male and female phenotypes. This basic paradigm was formulated by Alfred Jost to explain the results of castration experiments in fetal rabbits. If the gonads (ovaries or testes) were removed before sexual differentiation, female sexual differentiation inevitably ensued. The male pathway could be partly restored by testosterone implants, suggesting that hormones produced by the testes mediate male sexual development. Thus, the concept arose that the testes induce a male pattern of differentiation on an embryo that otherwise would follow the female pathway. Cytogenetic studies shortly thereafter showed that the critical genetic determinant of sex is the presence or absence of the Y chromosome, leading to the proposal that the Y chromosome directs the gonad to differentiate into a testis, which then produces hormone(s) that cause male sexual differentiation. The chromosomal sex of the embryo generally corresponds to its phenotypic sex. Occasionally, however, the process of sexual differentiation goes awry, resulting in individuals with disorders of sexual differentiation (DSD). Clinically recognized disorders of sexual development occur at many levels, ranging from relatively common disorders in the terminal steps of male differentiation (e.g., testicular descent, growth of the penis) to more fundamental abnormalities that lead to varying degrees of ambiguity of phenotypic sex. Although most of these abnormalities impair reproduction, they usually are not life threatening. Thus, humans and experimental animals with naturally occurring defects in sexual differentiation survive to reach the attention of physicians and scientists. This chapter reviews the sequence of events in normal sexual development and describes disorders of this process — many of which result from single-gene mutations — that have provided valuable insights into the mechanisms of sexual differentiation. Normally, human somatic cells have 22 pairs of autosomes and 1 pair of sex chromosomes.