Testicular descent: A review of a complex, multistaged process to identify potential hidden causes of UDT

Abstract Objectives Cryptorchidism is the most common genitourinary birth defect in live newborn males and is considered as an important risk factor for testicular germ cell tumors and infertility. The Androgen Receptor gene is important in this pathology due to its participation, mainly, in the inguinoscrotal phase of testicular descent. We determine the length of the CAG tract in the Androgen Receptor (AR) gene in Mexican patients with nonsyndromic cryptorchidism. Methods One hundred and 15 males were included; of these, 62 had nonsyndromic cryptorchidism and 53 were healthy volunteers. DNA was extracted from a peripheral blood samples, subsequently, the CAG tract in exon 1 of AR gene was amplified by PCR and sequenced. Results Mexican patients with nonsyndromic cryptorchidism presented 25.03 ± 2.58 repeats of CAG tract in the AR gene compared to 22.72 ± 3.17 repeats of CAG tract in Mexican healthy individuals (p≤0.0001; t value of 4.3). Furthermore, the deletion of codon 57 that corresponds to the deletion of a leucine residue at position 57 (Del L57) in the AR gene was found for the first time in a nonsyndromic cryptorchidism patient. This molecular alteration has been related previously to testicular germ cell tumor (TGCT). Conclusions The CAG tract in the AR gene is longer in patients with nonsyndromic cryptorchidism than in healthy individuals, supporting the association between this polymorphism of the AR gene and nonsyndromic cryptorchidism in the Mexican population.

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Association of antimullerian hormone with the size of the appendix testis, the androgen and estrogen receptors and their expression in the appendix testis, in congenital cryptorchidism

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2021-0240 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Xenophon Sinopidis ◽

Eirini Kostopoulou ◽

Andrea Paola Rojas-Gil ◽

Antonios Panagidis ◽

Eleni Kourea ◽

...

Keyword(s):

Estrogen Receptor ◽

Receptor Expression ◽

Testicular Descent ◽

Antimullerian Hormone ◽

Mullerian Ducts ◽

Score Method ◽

Antimüllerian Hormone ◽

Unilateral Cryptorchidism ◽

Appendix Testis

Abstract Objectives Antimullerian hormone (AMH) causes regression of the mullerian ducts in the male fetus. The appendix testis (AT) is a vestigial remnant of mullerian duct origin, containing both androgen (AR) and estrogen (ER) receptors. The role of both AMH and AT in testicular descent is yet to be studied. We investigated the possible association of AMH with AT size, the AR and ER, and their expression in the AT, in congenital cryptorchidism. Methods A total of 26 patients with congenital unilateral cryptorchidism and 26 controls with orthotopic testes were investigated, and 21 ATs were identified in each group. AMH and insulin-like three hormone (INSL3) concentrations were measured with spectrophotometry. AR and ER receptor expression was assessed with immunohistochemistry using monoclonal antibodies R441 for AR and MAB463 for ER. For the estimation of receptor expression, the Allred Score method was used. Results AMH concentrations did not present significant differences between patients with congenital cryptorchidism and the controls. Also, no correlation was found between AMH, INSL3, and AT length. Allred scores did not present significant differences. However, expression percentiles and intensity for both receptors presented significant differences. Three children with cryptorchidism and the highest AMH levels also had the highest estrogen receptor scores in the AT. Conclusions No association was found between AMH and the studied major parameters. However, higher AMH concentrations, in combination with higher estrogen receptor scores in the AT, may play a role in cryptorchidism in some children. Larger population samples are needed to verify this observation.

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Normative Values for Testicular Descent from Infancy to Adulthood

Hormone Research ◽

10.1159/000182710 ◽

1993 ◽

Vol 39 (3-4) ◽

pp. 118-121 ◽

Cited By ~ 1

Author(s):

J. Sack ◽

B. Reichman ◽

A. Fix

Keyword(s):

Normative Values ◽

Testicular Descent

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Wolffian duct and epididymal agenesis fails to prevent testicular descent

Pediatric Surgery International ◽

10.1007/bf00174350 ◽

1990 ◽

Vol 5 (6) ◽

Cited By ~ 6

Author(s):

Gordon Baikie ◽

JohnM. Hutson

Keyword(s):

Wolffian Duct ◽

Testicular Descent

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Using corticosteroid creams in baby boys does not affect testicular descent

Inpharma Weekly ◽

10.2165/00128413-199007490-00050 ◽

1990 ◽

Vol &NA; (749) ◽

pp. 18

Author(s):

&NA;

Keyword(s):

Testicular Descent

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Rapid evolution and molecular convergence in cryptorchidism-related genes associated with inherently undescended testes in mammals

BMC Ecology and Evolution ◽

10.1186/s12862-021-01753-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Simin Chai ◽

Ran Tian ◽

Juanjuan Bi ◽

Shixia Xu ◽

Guang Yang ◽

...

Keyword(s):

Muscle Development ◽

Rapid Evolution ◽

Genetic Material ◽

Comparative Genomic ◽

Testicular Descent ◽

Ancestral State ◽

Undescended Testes ◽

Genomic Analyses ◽

Genetic Mechanisms ◽

Molecular Convergence

Abstract Background The mammalian testis is an important male exocrine gland and spermatozoa-producing organ that usually lies in extra-abdominal scrotums to provide a cooler environment for spermatogenesis and sperm storage. Testicles sometimes fail to descend, leading to cryptorchidism. However, certain groups of mammals possess inherently ascrotal testes (i.e. testes that do not descend completely or at all) that have the same physiological functions as completely descended scrotal testes. Although several anatomical and hormonal factors involved in testicular descent have been studied, there is still a paucity of comprehensive research on the genetic mechanisms underlying the evolution of testicular descent in mammals and how mammals with ascrotal testes maintain their reproductive health. Results We performed integrative phenotypic and comparative genomic analyses of 380 cryptorchidism-related genes and found that the mammalian ascrotal testes trait is derived from an ancestral scrotal state. Rapidly evolving genes in ascrotal mammals were enriched in the Hedgehog pathway—which regulates Leydig cell differentiation and testosterone secretion—and muscle development. Moreover, some cryptorchidism-related genes in ascrotal mammals had undergone positive selection and contained specific mutations and indels. Genes harboring convergent/parallel amino acid substitutions between ascrotal mammals were enriched in GTPase functions. Conclusions Our results suggest that the scrotal testis is an ancestral state in mammals, and the ascrotal phenotype was derived multiple times in independent lineages. In addition, the adaptive evolution of genes involved in testicular descent and the development of the gubernaculum contributed to the evolution of ascrotal testes. Accurate DNA replication, the proper segregation of genetic material, and appropriate autophagy are the potential mechanisms for maintaining physiological normality during spermatogenesis in ascrotal mammals. Furthermore, the molecular convergence of GTPases is probably a mechanism in the ascrotal testes of different mammals. This study provides novel insights into the evolution of the testis and scrotum in mammals and contributes to a better understanding of the pathogenesis of cryptorchidism in humans.

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Mullerian inhibiting substance production and testicular migration and descent in the pouch young of a marsupial

Development ◽

10.1242/dev.104.4.549 ◽

1988 ◽

Vol 104 (4) ◽

pp. 549-556 ◽

Cited By ~ 2

Author(s):

J.M. Hutson ◽

G. Shaw ◽

W.S. O ◽

R.V. Short ◽

M.B. Renfree

Keyword(s):

Tammar Wallaby ◽

Testicular Descent ◽

Future Studies ◽

Macropus Eugenii ◽

Müllerian Inhibiting Substance ◽

Sequence Of Events ◽

Testicular Differentiation ◽

Testicular Migration ◽

Australian Marsupial ◽

Mullerian Inhibiting Substance

The ontogeny of Mullerian inhibiting substance (MIS) production by the developing testis of an Australian marsupial, the tammar wallaby (Macropus eugenii), was determined during pouch life using an organ-culture bioassay of mouse fetal urogenital ridge. This information was related to the morphological events during testicular migration and descent. MIS biological activity was found in testes (but not ovaries or liver) of pouch young from 2 to 85 days of age. MIS production had commenced by day 2, which is within a day of the first gross morphological signs of testicular differentiation. Mullerian duct regression occurred between 10 and 30 days, which partly coincided with testicular migration to the inguinal region and enlargement of the gubernacular bulb (15 to 30 days). These observations are consistent with the hypothesis that MIS may be involved in testicular transabdominal migration. The epididymis commenced development and growth only after the testis had descended through the inguinal ring. This provides no support for the suggestion that the epididymis is involved in testicular descent into the scrotum. The basic sequence of events in post-testicular sexual differentiation in the wallaby is sufficiently similar to that seen in eutherian mammals to make it an excellent experimental model for future studies of testicular differentiation, migration and descent.

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