https://apps.who.int/iris/bitstream/10665/78102/1/WHO_HSE_PHE_IHE_2013.1_eng.pdf

State of the Science of Endocrine Disrupting Chemicals - 2012

Masculinization depends on adequate production of testosterone by the fetal testis within a specific "masculinization programming window." Disorders resulting from subtle deficiencies in this process are common in humans, and environmental exposures/lifestyle could contribute causally because common therapeutic and environmental compounds can affect steroidogenesis. This evidence derives mainly from rodent studies, but because there are major species differences in regulation of steroidogenesis in the fetal testis, this may not always be a guide to potential effects in the human. In addition to direct study of the effects of compounds on steroidogenesis, information also derives from study of masculinization disorders that result from mutations in genes in pathways regulating steroidogenesis. This review addresses this issue by critically reviewing the comparative timing of production and regulation of steroidogenesis in the fetal testis of humans and of rodents and its susceptibility to disruption; where there is limited information for the fetus, evidence from effects on steroidogenesis in the adult testis is considered. There are a number of fundamental regulatory differences between the human and rodent fetal testis, most notably in the importance of paracrine vs. endocrine drives during masculinization such that inactivating LH receptor mutations block masculinization in humans but not in rodents. Other large differences involve the steroidogenic response to estrogens and GnRH analogs and possibly phthalates, whereas for other compounds there may be differences in sensitivity to disruption (ketoconazole). This comparison identifies steroidogenic targets that are either vulnerable (mitochondrial cholesterol transport, CYP11A, CYP17) or not (cholesterol uptake) to chemical interference.

/pdf/steroidogenesis-in-the-fetal-testis-and-its-susceptibility-19p4rksil9.pdf

Steroidogenesis in the Fetal Testis and Its Susceptibility to Disruption by Exogenous Compounds

Cryptorchidism and hypospadias are common genital birth defects that affect 2–9% and 0.2–1% of male newborns, respectively. The incidence of both defects shows large geographic variation, and in several countries increasing trends have been reported. The conditions share many risk factors, and they are also interlinked to the risk of testis cancer and poor semen quality. Testicular Dysgenesis Syndrome (TDS) may underlie many cases of all these male reproductive health problems. Genetic defects in androgen production or action can cause both cryptorchidism and hypospadias, but these are not common. A monogenic reason for cryptorchidism or hypospadias has been identified only in a small proportion of all cases. Environmental effects appear to play a major role in TDS. Exposure to several persistent chemicals has been found to be associated with the risk of cryptorchidism, and exposure to anti-androgenic phthalates has been shown to be associated with hormonal changes predisposing to male reproductive problems. Despite progress in identification of endocrine-disrupting substances, we are still far from knowing all the risk factors for these birth defects, and advice for prevention must be based on precautionary principles. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc.

Cryptorchidism and hypospadias as a sign of testicular dysgenesis syndrome (TDS): Environmental connection

In the past 200 years, an enormous number of synthetic chemicals with diverse structural features have been produced for industrial, medical and domestic purposes These chemicals, originally thought to have little or no biological toxicity, are widely used in our daily lives as well as are commonly present in foods It was not until the first World Wildlife Federation Wingspread Conference held in 1994 were concerns about the endocrine disrupting (ED) effects of these chemicals articulated The potential hazardous effects of endocrine disrupting chemicals (EDCs) on human health and ecological well-being are one of the global concerns that affect the health and propagation of human beings Considerable numbers of studies indicated that endocrine disruption is linked to "the developmental basis of adult disease," highlighting the significant effects of EDC exposure on a developing organism, leading to the propensity of an individual to develop a disease or dysfunction in later life In this review, we intend to provide environmental, epidemiological and experimental data to associate pollutant exposure with reproductive disorders, in particular on the development and function of the male reproductive system Possible effects of pollutant exposure on the processes of embryonic development, like sex determination and masculinization are described In addition, the effects of pollutant exposure on hypothalamus-pituitary-gonadal axis, testicular signaling, steroidogenesis and spermatogenesis are also discussed

https://www.tandfonline.com/doi/pdf/10.4161/spmg.1.3.18019

Endocrine disrupting chemicals: Multiple effects on testicular signaling and spermatogenesis.

What is new in cryptorchidism and hypospadias--a critical review on the testicular dysgenesis hypothesis.

Hypospadias is one of the most common congenital anomalies in the United States, occurring in approximately 1 in 125 live male births. Embryological studies have demonstrated that, depending on where the urethral development arrests, the meatal opening can be anywhere along the shaft of the penis or, in more severe forms, within the scrotum or in the perineum. Currently, the only available treatment is surgery. If left uncorrected, especially in its severe form, there is risk of infertility and psychological effects, such as avoidance of intimate relationships. The cause of hypospadias is largely unknown; however, current epidemiology and laboratory studies have shed new light into the etiology of hypospadias. With recent advancements in molecular biology and microarray technology, it appears that hypospadias is potentially related to disrupted gene expression. Specifically, some of the environmental chemicals are acting as antiandrogens and interfere directly with the action of testosterone-related gene expression. In this paper, we briefly review the normal development of male external genitalia and the prevalence and environmental risk factors related to hypospadias. In addition, we discuss some of the recent laboratory findings that contribute to our current understanding of this disease.

https://onlinelibrary.wiley.com/doi/pdf/10.2164/jandrol.108.004945

Endocrine disruptors, genital development, and hypospadias.

Urothelium-derived Sonic hedgehog promotes mesenchymal proliferation and induces bladder smooth muscle differentiation.

Does severity of renal scarring on DMSA scan predict abnormalities in creatinine clearance

Cerebral palsy (CP) is a non-progressive injury of the brain that affects muscle movement and coordination secondary to anoxia that occurred during the perinatal period. Babies who are premature, low birth weight, and those who sustained perinatal infection, seizure, or intracranial hemorrhage are at an increase risk of being affected. The injury mainly involves the motor control center of the brain; therefore, presents clinically with variable physical impairments, ranging from delayed gross or fine motor development to altered muscle tone and gait. With public awareness and research, the full spectrum of intelligence and capabilities of these children is now being appreciated. Studies have shown that with supportive caretakers, many of these children go on to enjoy near-normal adult lives. Therefore, it is imperative that their physical disabilities are identified and managed properly. In this review, we will focus primarily on urologic evaluation and management of patients with CP, with a brief review of normal bladder physiology and voiding pattern.

Management of neurogenic bladder in patients with cerebral palsy

Mp18-09 liposomal bupivacaine plus bupivacaine vs. bupivacaine alone in pediatric patients undergoing urologic surgery: preliminary report from the baby orioles trial

Ming Hsien Wang

Papers

Endocrine disruptors, genital development, and hypospadias.

Urothelium-derived Sonic hedgehog promotes mesenchymal proliferation and induces bladder smooth muscle differentiation.

Does severity of renal scarring on DMSA scan predict abnormalities in creatinine clearance

Management of neurogenic bladder in patients with cerebral palsy

Mp18-09 liposomal bupivacaine plus bupivacaine vs. bupivacaine alone in pediatric patients undergoing urologic surgery: preliminary report from the baby orioles trial