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Production of sperm and androgens is the main function of the testis. This depends on normal development of both testicular somatic cells and germ cells. A genetic program initiated from the Y chromosome gene sex-determining region Y (SRY) directs somatic cell specification to Sertoli cells that orchestrate further development. They first guide fetal germ cell differentiation toward spermatogenic destiny and then take care of the full service to spermatogenic cells during spermatogenesis. The number of Sertoli cells sets the limits of sperm production. Leydig cells secrete androgens that determine masculine development. Testis development does not depend on germ cells; that is, testicular somatic cells also develop in the absence of germ cells, and the testis can produce testosterone normally to induce full masculinization in these men. In contrast, spermatogenic cell development is totally dependent on somatic cells. We herein review germ cell differentiation from primordial germ cells to spermatogonia and development of the supporting somatic cells. Testicular descent to scrota is necessary for normal spermatogenesis, and cryptorchidism is the most common male birth defect. This is a mild form of a disorder of sex differentiation. Multiple genetic reasons for more severe forms of disorders of sex differentiation have been revealed during the last decades, and these are described along with the description of molecular regulation of testis development.

Despite clinical guidelines calling for repetitive examination of testicular position during childhood, little is known of normal changes in testicular position during childhood, let alone factors that control it.

Although semen quality is an important determinant of fertility, defining clear thresholds for normal ranges has proven difficult. According to 'time to pregnancy' studies, fecundity starts to decline when sperm concentrations fall below 30–55 × 106/ml, whereas the WHO criterion for normal values is currently 15 × 106/ml. Multiple studies over the past 15 years have reported median sperm concentrations of 41–55 × 106/ml in young men (mean age 18–21 years) from the general population, suggesting that many of them have suboptimal semen quality. Sperm numbers remain fairly constant between 19 and 29 years of age, which points to the importance of developmental effects. Discussion on whether population semen quality has declined has continued for decades, as regional differences in trends have been noted. The reasons for poor semen quality and adverse trends are not well established, but some associations suggest a causal relationship, for example, with maternal smoking during pregnancy. The role of chemical exposures leading to endocrine disruption and detrimental reproductive effects has been in the focus of research during the past 20 years. Identification of exposures that affect fertility could provide opportunities for effective prevention of reproductive health problems.

Semen quality has declined especially among Western men. Experimental and epidemiological studies have shown potential links between exposure to environmental toxicants and poor male fertility. Some environmental exposures in utero can disrupt fetal testicular function and result in cryptorchidism, low semen quality, low serum testosterone levels, and low fertility. Environmental exposure in childhood and adulthood can also adversely affect germ cells, Sertoli cells, Leydig cells, or the hypothalamic-pituitary-testicular axis, resulting in impaired male fertility. In this review, we report the latest results from human studies that investigated the role of endocrine disrupting chemicals, heavy metals, tobacco smoking, alcohol drinking, and use of marijuana in low semen quality and impaired male fertility. Current evidence suggests the relationship between these environmental factors and low male fertility; however, some factors showed conflicting results which need further investigation.

Context:The pattern of testicular growth during puberty may provide important information about early testicular damage and reproductive potential in adulthood.Objective:To evaluate pubertal testicular growth in boys with congenital cryptorchidism and controls.Design:Longitudinal case-control study.Setting:Andrological Research Center, University of Turku.Participants:Altogether, 119 boys participated: 51 cases with a history of congenital cryptorchidism and 65 controls fulfilled the inclusion criteria.Intervention:None.Main Outcome Measures:Testicular volume by an orchidometer (mL) and ultrasound (mL), testicular length by a ruler (mm), and onset of pubertal testicular growth (y). Longitudinal testicular growth was analyzed with a nonlinear mixed-effect model.Results:The mean age of the onset of pubertal testicular growth (age at the attainment of >3 mL by orchidometer) was 11.7 and 11.8 years in cryptorchid cases and controls, respectively. The difference between cases and controls was not significant. Modeled postpubertal testicular size was smaller among bilaterally and unilaterally undescended testis than in controls. There was a high level of agreement between testicular sizes of 3 mL by orchidometer and 25 mm by ruler as cut-offs in definition of the onset of puberty. An orchidometer size of 3 mL and ruler length of 25 mm corresponded to 1.6 and 1.7 mL by ultrasound (with Lambert's formula), respectively.Conclusions:Testicular growth in puberty was impaired in congenitally cryptorchid boys. This suggests a poor perinatal development of the cryptorchid testis. The timing of the onset of pubertal testicular growth, however, did not differ which suggests an intact hypothalamic-pituitary axis.

Congenital cryptorchidism, that is, undescended testis, is one of the most common urogenital abnormalities observed in newborn boys. In addition to the congenital form, there is also acquired form of cryptorchidism. Fertility potential of patients with cryptorchidism has been evaluated by testicular histology and volume, semen quality, reproductive hormone levels, time to conception, and paternity rates. Cryptorchidism is associated with abnormalities in testicular development, and early treatment is recommended to optimize the fertility potential of the patients.

Testes descend to the scrotum normally before birth. When they fail to do so, the boy is cryptorchid and has an increased risk for testicular germ cell cancer and subfertility later in life. Early correction of maldescent by orchiopexy operation improves the spermatogenetic capacity of the testis but does not return the testicular cancer risk to the control level. Testicular descent is regulated by testis-derived hormones testosterone and insulin-like peptide 3. Cryptorchidism can therefore be considered a symptom of impaired testicular function that may also be linked to other testicular diseases, such as germ cell cancer and subfertility. Early orchiopexy can alleviate the effects of cryptorchidism on spermatogenesis, but alertness for testicular cancer should be maintained. In searching the genetic and environmental reasons for these diseases, it is useful to consider their connection with each other.

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.

Objective: Infant boys show a brief activation of their hypothalamic–pituitary–gonadal axis shortly after birth, the physiological significance of which is poorly understood. The objective of the study was to investigate the correlation between endogenous testosterone levels and penile size and growth.Design: Prospective, longitudinal population-based study taking place at two large primary obstetric centres at the University Hospitals of Copenhagen, Denmark, and Turku, Finland.Methods: Infant boys, 728 Danish and 1234 Finnish, underwent clinical examinations at 0, 3, 18 and 36 months in Denmark and at 0, 3 and 18 months in Finland with blood samples taken at 3 months (n= 630). Penile length and growth were registered and reproductive hormones (testosterone, sex hormone binding globulin, oestradiol) were analysed.Results: Penile length increased from birth (3.49±0.4 cm) to 3 years of age (4.53±0.51 cm) with the highest growth velocity from birth to 3 months (1.0 mm/month). Penile length and growth were significantly, positively correlated to serum testosterone (r= 0.31 and 0.076, P= 0.006 and 0.001 respectively) and to free testosterone index (r= 0.385 and 0.094, P= 0.0001 and 0.0001 respectively).Conclusions: We found that endogenous testosterone was significantly associated with penile size and growth rate in infant boys. Thus, the postnatal surge in reproductive hormones appears to be important for genital growth. Our data may serve as an updated reference for normal penile length in Caucasian boys up to 3 years of age.