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

Background/purpose: What causes normal descent of the testis in a fetus, and what goes wrong with this complex process to cause undescended testes (UDT), or cryptorchidism? Over the last 2 decades, most authors searching for the cause(s) of UDT have looked at the 2 main hormones involved, insulin-like hormone 3 (Insl3) and testosterone (T)/ dihydrotestosterone (DHT), and their known upstream (hypothalamic-pituitary axis) and intracellular 'downstream' pathways. Despite these detailed searches, the genetic causes of UDT remain elusive, which suggest the aetiology is multifactorial, and/or we are looking in the wrong place.

Methods: In this review we highlight the intricate morphological steps involved in testicular descent, which we propose may contain the currently 'idiopathic' causes of UDT.

BDNF is upregulated by androgen in the inguinal fat pad of immature mice and may regulate inguinoscrotal testicular descent.

Background: Androgens control rodent inguinoscrotal testicular descent during a "programming window" (E12-17). It is proposed that androgen masculinises the genitofemoral nerve, but the mechanism remains unknown. We investigate androgen receptor (AR)-containing target organs: inguinal fat pad (IFP) and mammary bud (MB), supplied by the genitofemoral nerve, hypothesizing that neurotrophic factors may retrogradely masculinise the GFN.

Frequency of inguinal herniotomy in Australia (1998-2017).

Background/aim: Closure of the processus vaginalis (PV) is considered as the last step of testicular descent. Therefore, patent processus vaginalis (PV), and inguinal hernias are linked to cryptorchidism. As the National Australian incidence of orchidopexy has decreased over the previous 20 years, we aimed to explore the incidence of inguinal herniotomy (including hydrocele) over time in Australia.

An immunohistochemical analysis of the effects of androgen receptor knock out on gubernacular differentiation in the mouse.

Aim: Cryptorchidism affects 2%-4% of newborn boys and causes infertility and cancer. While normal androgen function is required for successful inguinoscrotal descent, its exact role on gubernacular morphology remains unidentified. We aimed to decipher the effect of androgen blockade on the gubernaculum and surrounding structures.

Undescended testis: What paediatricians need to know.

Undescended testis (UDT) occurs when something goes wrong with testicular descent from high in the abdominal cavity to the scrotum. Normal descent occurs in two steps, with the transabdominal phase controlled by a new testicular hormone, insulin-like hormone 3, and the inguinoscrotal phase controlled by androgens. The latter phase requires a complex process of migration from the inguinal abdominal wall to the scrotum and is commonly defective, leading to the high incidence (2-4%) of UDT at birth.

Frequency of revision orchidopexy in Australia 1995-2014.

Background/aim: International criteria currently suggest orchidopexy at 6-12months for congenital undescended testis (UDT). Some children require repeat orchidopexy for recurrent UDT. This study aimed to assess practice in Australia over a 20-year period.

Postnatal Germ Cell Development in the Cryptorchid Testis: The Key to Explain Why Early Surgery Decreases the Risk of Malignancy.

Purpose:  Cryptorchidism is a risk factor for testicular malignancy and surgical treatment lowers this risk. This study aimed to investigate the germ cell behavior in prepubertal cryptorchid testes using immunohistochemical markers for germ cell malignancy to understand how early orchiopexy may possibly prevent cancer developing.

Materials And Methods:  Histology sections from 1,521 consecutive testicular biopsies from 1,134 boys aged 1 month to 16.

Undescended testes: Diagnosis and timely treatment in Australia (1995-2014).

Background: Routine primary care checks in infants and prepubertal boys aim for early detection and intervention of undescended testes (UDT). Congenital and acquired UDT cause infertility, and congenital UDT also increases testicular cancer risk. We examined 20 years of Australian orchidopexy data (1995-2014) to explore the national orchidopexy operation rates over time.

What Animal Models of Testicular Descent and Germ Cell Maturation Tell Us about the Mechanism in Humans.

Testicular descent occurs in most mammals in two main steps that have different hormonal control and anatomical processes. The evolution of testicular descent reveals the same basic processes in humans and animals, with minor differences in timing and anatomy, especially the location of the scrotum and the processus vaginalis. Animal models are useful as they reveal some embryological processes that cannot be studies easily in humans, such as the potential role of the mammary line and the role of the genitofemoral nerve.

The undescended testis: Clinical management and scientific advances.

Undescended testes (UDT), where one or both testes fail to migrate to the base of the scrotum, can be congenital (2-5% of newborn males) or acquired (1-2% of males). The testis may be found in any position along its usual line of descent. Cryptorchidism affects the developing testicular germ cells and increases the risk of infertility and malignancy.

Neurotrophin signaling in a genitofemoral nerve target organ during testicular descent in mice.

Background/aim: It has been proposed that androgens control inguinoscrotal testicular descent via release of calcitonin gene-related peptide (CGRP) from a masculinised genitofemoral nerve (GFN). As there are androgen receptors in the inguinoscrotal fat pad (IFP) during the window of androgen sensitivity (E14-17 in mouse embryos), we tested the hypothesis that neurotrophins in the IFP may masculinise the sensory fibers of the GFN supplying the gubernaculum and IFP prior to gubernacular migration.

Methods: Androgen-receptor knockout (ARKO) and wild-type (WT) mouse embryos were collected at E17, with ethical approval (AEC 734).

Molecular signals governing cremaster muscle development: clues for cryptorchidism.

Background/aim: Cryptorchidism affects 2-4% of newborn boys. Testicular descent requires the gubernaculum to differentiate into cremaster muscle (CM) during androgen-mediated inguino-scrotal descent, but the cellular mechanisms regulating this remodeling remain elusive. β-Catenin, a marker of canonical Wnt signaling, promotes myogenic genes and cellular adhesion.