The effect of 5α-reductase-2 deficiency on human fertility

Abstract

A most interesting and intriguing male disorder of sexual differentiation is due to 5α-reductase-2 isoenzyme deficiency. These males are born with ambiguous external genitalia due to a deficiency in their ability to catalyze the conversion of testosterone to dihydrotestosterone (DHT). DHT is a potent androgen responsible for differentiation of the urogenital sinus and genital tubercle into the external genitalia, urethra and prostate. Affected males are born with a clitoral-like phallus, bifid scrotum, hypospadias, blind shallow vaginal pouch from incomplete closure of the urogenital sinus and a rudimentary prostate. At puberty, the surge in mainly testosterone production prompts virilization, causing most to choose gender reassignment to male. Fertility is a challenge for affected men for several reasons. Uncorrected cryptorchidism is associated with low sperm production, and there is evidence of defective transformation of spermatogonia into spermatocytes. The underdeveloped prostate and consequent low semen volumes affect sperm transport. Additionally, semen may not liquefy due to a lack of prostate-specific antigen. In this review, we discuss the 5α-reductase-2 deficiency syndrome and its impact on human fertility.

Expression profiles of differentially expressed genes affecting fecundity in goat ovarian tissues

“…It is mainly expressed in the reproductive system and prostate tissue (Ellsworth et al, 1995), has a high affinity for steroid substrates, and participates in the reproductive system and prostate tissue development (Yokoi et al, 1998). SRD5A2 is also closely related with fertilization (Kang et al, 2014), sexual abnormality (Kostyrko et al, 1994), prostate disease (Kaefer et al, 1996;Akalu et al, 1999), polycystic ovary syndrome (Goodarzi et al, 2006), and cancer (Akalu et al, 1999;Li et al, 2013). Studies of human SRD5A2 deficiency pedigrees showed that male patients displayed pseudo-hermaphroditism, while female patients had reduced fertility (Hochberg et al, 1996).…”

Paternity in 5α-Reductase-2 Deficiency: Report of Two Brothers with Spontaneous or Assisted Fertility and Literature Review

“…In addition, patients with 5α-reductase-2 deficiency likely present brain androgenization by direct testosterone action in prenatal life as well as in the first months of life [Cohen-Kettenis et al, 2005;Kang et al, 2014] when minipuberty occurs [Grumbach, 2005]. This early testosterone action on the brain may contribute to the high rate of female-to-male role changes at adolescence in individuals assigned the female sex in infancy and the male gender orientation in adulthood [Hiort et al, 2003;Cohen-Kettenis et al, 2005;Kang et al, 2014;Mendonca et al, 2016].…”

“…However, fertility remains a challenge for men with 5α-reductase-2 deficiency [Kang et al, 2014], resulting in very few reports of documented paternity ( Table 2 ). Both an impaired second step of germ cell maturation, resulting in defective transformation of spermatogonia into spermatocytes [Hadziselimovic and Dessouky, 2008], and an adverse impact of intra-inguinal/intra-abdominal temperature on spermatogenesis may occur [Kang et al, 2014].…”

“…paired, requiring assisted reproductive technologies to reach fatherhood [Costa et al, 2012, Kang et al, 2014.…”

Fertility counseling and preservation: considerations for the pediatric endocrinologist

“…Patients raised as male will retain their testicles, however still frequently suffer from poor fertility (60). Fertility is also impaired in other DSD such as rare forms of CAH, gonadal dysgenesis, and 5-alpha-reductase deficiency (64,65). However, a recent study showed that gonads removed from patients with a variety of DSD including AIS, © Translational Pediatrics.…”