PEDIATRICS / CLINICAL RESEARCH
 
KEYWORDS
TOPICS
ABSTRACT
Introduction:
The etiology of cryptorchidism is still not fully elucidated, but several hypotheses have been proposed. One of the latest concerns is the involvement of metalloproteinase ADAMTS16 in testis descent. The aim of this study was to evaluate both expression and occurrence of selected polymorphisms of metalloproteinase ADAMTS16 in patients diagnosed with cryptorchidism.

Material and methods:
The study group consisted of 158 boys (mean age: 4.1 ±2.04 years) who underwent surgery due to undescended testis. Tissue samples from patients with cryptorchidism were obtained from the cremaster muscle, gubernaculum and hernial sac. The reference group consisted of 123 age-related subjects (mean age: 4.1 ±2.41 years) who had no cryptorchidism and underwent surgery for other reasons. Tissue samples from controls were obtained from the cremaster muscle and hernial sac.

Results:
The obtained data indicate that patients with undescended testis have significantly lower expression of Adamts16, especially in the gubernaculum. We also demonstrated a tendency that Adamts16 expression depends on the age of patients; the older the patient was, the higher was the observed expression of Adamts16. These studies also established that polymorphisms rs16875319, rs16875122, and rs58353460 in the Adamts16 gene are not a major determinant to develop cryptorchidism while rs16875054 is associated with increased risk.

Conclusions:
These studies highlight ADAMTS16 involvement in cryptorchidism and confirm data obtained in animal models.
REFERENCES (31)
1.
Niedzielski J, Oszukowska E, Słowikowska-Hilczer J. Undescended testis – current trends and guidelines: review of the literature. Arch Med Sci 2016; 12: 667-77.
 
2.
Leslie SW, Sajjad H, Villanueva CA. Cryptorchidism. Treasure Island (FL): StatPearls Publishing LLC. 2020.
 
3.
Braga LH, Lorenzo AJ. Cryptorchidism: a practical review for all community healthcare providers. Canad Urol Assoc J 2017; 1-2 Suppl 1: 26-32.
 
4.
Urh K, Kolenc Z, Hrovat M, Svet L, Dovč P, Kunej T. Molecular mechanisms of syndromic cryptorchidism: data synthesis of 50 studies and visualization of gene-disease network. Front Endocrinol 2018; 9: 425-35.
 
5.
Ivell R, Hartung S. The molecular basis of cryptorchidism. Mol Hum Reprod 2003; 9: 175-81.
 
6.
Abdul-Majeed S, Mell B, Nauli SM, Joe B. Cryptorchidism and infertility in rats with targeted disruption of the Adamts16 locus. PLoS One 2014; 9: e100967.
 
7.
Liu Y, Min D, Bolton T, et al. Increased matrix metalloproteinases-9 predicts poor wound healing in diabetic foot ulcers. Diabetes Care 2009; 32: 117-9.
 
8.
Aplin AC, Zhu WH, Fogel E, Nicosia RF. Vascular regression and survival are differentially regulated by MT1-MMP and TIMPs in the aortic ring model of angiogenesis. Am J Physiol Cell Physiol 2009; 297: C471-80.
 
9.
Higa R, Kurtz M, Capobianco E, Martinez N, White V, Jawerbaum A. Altered matrix metalloproteinases and tissue inhibitors if metalloproteinases in embryos from diabetic rats during early organogenesis. Reprod Toxicol 2011; 32: 449-62.
 
10.
Nghia TVL, Xue M, Castelnoble LA, Jackson CJ. The dual personalities of matrix metalloproteinases in inflammation. Front Biosc 2007; 12: 1475-87.
 
11.
Stevens LJ, Page-McCaw A. A secreted MMP is required for reepithelialisation during wound healing. Mol Biol Cell 2012; 23: 1068-79.
 
12.
Ruiz V, Ordonez RM, Berumen J, et al. Inbalanced collagenases/TIMP-1 expression and epithelial apoptosis in experimental lung fibrosis. Am J Physiol Cell Physiol 2003; 285: L1026-36.
 
13.
Yamashita CM, Dolgonos L, Zemans RL, et al. Matrix metalloproteinase 3 is a mediator of pulmonary fibrosis. Am J Pathol 2011; 179: 1733-45.
 
14.
Dev K, Frank L. Expression of ADAMs (a disintegrin and metalloproteases) and TIMP-3 (tissue inhibitor of metalloproteinase-3) in human prostatic adenocarcinomas. Int J Oncol 2003; 23: 1365-71.
 
15.
Nagase H, Visse R, Murphy G. Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res 2006; 69: 562-73.
 
16.
Trojanek J. Metaloproteinazy macierzy zewnątrzkomórkowej i ich tkankowe inhibitory. Postep Biochem 2015; 61: 356-63.
 
17.
Groblewska M, Tycińska A, Mroczko B, Musiał W, Szmitkowski M. Metaloproteinazy macierzy zewnątrzkomórkowej w chorobach układu krążenia. Pol Merk Lek 2011; 178: 235-40.
 
18.
Mead TJ, Apte SS. ADAMTS proteins in human disorders. Matrix Biol 2018; 71-72: 225-39.
 
19.
Saran K, Nithya R, Ruowen. Emerging roles of ADAMTSs in angiogenesis and cancer. Cancers 2012; 4: 1252-99.
 
20.
Bonnans C, Chou J, Werb Z. Remodelling the extracellular matrix in development and disease. Nature reviews. Mol Cell Biol 2014; 15: 786-801.
 
21.
Gao S, De Geyter C, Kossowska K, Zhang H. FSH stimulates the expression of the ADAMTS-16 protease in mature human ovarian follicles. Mol Hum Reprod 2007; 13: 465-71.
 
22.
Jacobi CL, Rudigier LJ, Scholz H, Kirschner KM. Transcriptional regulation by the Wilms tumor protein, Wt1, suggests a role of the metalloproteinase Adamts16 in murine genitourinary development. J Biol Chem 2013; 288: 18811-24.
 
23.
Richter HE, Whitehead N, Arya L, et al. Genetic contributions to urgency urinary incontinence in women. J Urol 2015; 193: 2020-7.
 
24.
McGrath LM, Cornelis MC, Lee PH, et al. Genetic predictors of risk and resilience in psychiatric disorders: a cross-disorder genome-wide association study of functional impairment in major depressive disorder, bipolar disorder, and schizophrenia. Am J Med Genet B Neuropsychiatr Genet 2013; 162B: 779-88.
 
25.
Joe B, Saad Y, Dhindaw S, et al. Positional identification of variants of Adamts16 linked to inherited hypertension. Hum Mol Genet 2009; 18: 2825-38.
 
26.
Churchill JA, Buraundi S, Farmer PJ, et al. Gubernaculum as icebreaker: do matrix metalloproteinases in rodent gubernaculum and inguinal fat pad permit testicular descent? J Pediatr Surg 2011; 46: 2353-7.
 
27.
Chen N, Harisis GN, Farmer P, et al. Gone with the Wnt: the canonical Wnt signaling axis is present and androgen dependent in the rodent gubernaculum. J Pediatr Surg 2011; 46: 2363-9.
 
28.
Costa WS, Sampaio FJ, Favorito LA, Cardoso LE. Testicular migration: remodeling of connective tissue and muscle cells in human gubernaculum testis. J Urol 2002; 167: 2171-76.
 
29.
Zhao X, Onteru S, Saatchi M, Garrick D, Rothschild M. A genome-wide association study for canine cryptorchidism in Siberian Huskies. J Anim Breed Genet 2014; 131: 202-9.
 
30.
Dun MD, Anderson AL, Bromfield EG, et al. Investigation of the expression and functional significance of the novel mouse sperm protein, a disintegrin and metalloprotease with thrombospondin type 1 motifs number 10 (ADAMTS10). Int J Androl 2012; 35: 572-89.
 
31.
Schnellmann R, Sack R, Hess D, et al. A selective extracellular matrix proteomics approach identifies fibronectin proteolysis by a disintegrin-like and metalloprotease domain with thrombospondin type 1 motifs (ADAMTS16) and its impact on spheroid morphogenesis. Mol Cell Proteom 2018; 17: 1410-25.
 
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ISSN:1734-1922
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