ESPE Abstracts (2022) 95 P2-255

ESPE2022 Poster Category 2 Sex Differentiation, Gonads and Gynaecology, and Sex Endocrinology (30 abstracts)

Expression of Adam and Adamts Proteases Following Currative GnRHa Treatment for Cryptorchidism

Faruk Hadziselimovic 1 , Gilvidas Verkauskas 2,2 , Beata Vincel 2 & Michael Stadler 3


1Institute for cryptorchidism research, Liestal, Switzerland; 2Center of Childrens Surgery, Orthioedics, Traumatology, Vilnius, Lithuania; 3Friedrich Mischer Institute for Biomedical Research, Swiss Institute of Bioinformatics, Basel, Switzerland


Aim of the Study: ADAM/ADAMTS family members encode extracellular, multidomain proteolytic enzymes. Mutant Adamts16 mice display cryptorchidism and sterility. We hypothesize that gonadotropin-regulated ADAM/ADAMTS genes are involved in testicular development during mini-puberty.

Patients and Methods: Testicular biopsies for histological and RNA-Sequencing analysis from bilateral cryptorchid boys were analyzed. RNA samples were processed using a standard RiboMinus Gold/TrueSeq (Illumina) RNA protocol. Absence of spermatogonia was used to identify high infertility risk patients (HIR) who were randomized for treatment either with surgery in combination with GnRHa or surgery only. Four biopsies before (testis 1) and four after six months of GnRHa treatment (testis 2), were compared to three samples before (testis 1) and three samples after six months of surgery only.(testis 2) Main

Results: Surgery alone did not affect ADAM/ADAMTS expression. Expressions of Leydig cell specific ADAM23 as well as ADAMTS20 was decreased in HIR in comparison to LIR patients. (Table 1) Importantly, ADAMTS20 expression increases after GnRHa treatment. (Table 1) Furthermore, testis specific ADAM 29,30 and ADAMTS,16,18 genes showed identical expression level between HIR and LIR but were up-regulated by the GnRHa treatment. (Table 1) These genes are implicated in extracellular matrix remodeling and organogenesis.

Table 1. ADAM/ADAMTS-gene expression in LIR and HIR boys with cryptorchidism, before and after GnRHa treatment; FDR; false discovery rate, RPKM; median expression values expressed in reads per kilobase per million
Gene HIR/LIR (RPKM) log2FC / FDR -/+ GnRHa treatment (RPKM) log2FC / FDR
ADAM23 1.64/3.23 -1.0/0.0008 1.8/3.1 n.s.
ADAM29 0.16/0.11 n.s. 0.02/1.1 2.45/2.8E-05
ADAM30 0.14/0.10 n.s. 0.06/0.8 2.25/0.0002
ADAMS16 0.36/0.48 n.s. 0.41/1.13 0.73/0.033
ADAMTS18 015/0.35 n.s. 0.24/0.70 1.18/0.006
ADAMTS20 0.30/0.85 -1.67/0.0008 0.36/1.52 1.06/0.001

Conclusions: We show for the first time that testes from cryptorchid boys with abortive mini-puberty display decreased expression of ADAMTS20 and that expression is upregulated by GnRHa. This indicates a novel role for ADAMTS20 in the development of Ad spermatogonia and the establishment of fertility. Taken together, these results disclose involvement of ADAM23,29,30 and ADAMTS16,18,20 in a reproductive ADAM system that functions in fertility.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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