Causes of infertility in men with Down syndrome

Abstract

Men with Down syndrome are considered as infertile although the causes of infertility are not known in detail yet. Although this constitutes a general rule there are three confirmed cases of parenting by fathers with Down syndrome. Many investigators have addressed the causes of infertility and their studies indicate that the causes may be hormonal deficits, morphological alterations of the gonads, abnormal spermatogenesis, psychological and social factors related to the mental retardation. It is obvious that the extra chromosome 21 has a detrimental direct and indirect effect on the reproductive capacity of the affected male patient. But the definite cause of the insufficient and inadequate spermatogenesis remains to be discovered.

Low Bone Turnover and Low BMD in Down Syndrome: Effect of Intermittent PTH Treatment

“…The decreased bone turnover is unexpected, given the hypogonadism and infertility associated with the disorder in humans [28] and in Ts65Dn mice [29]. In fact, numerous published studies have yet to completely elucidate the pathophysiology of the infertility in men with Down syndrome [28], [30], [31], [32].…”

“…The decreased bone turnover is unexpected, given the hypogonadism and infertility associated with the disorder in humans [28] and in Ts65Dn mice [29]. In fact, numerous published studies have yet to completely elucidate the pathophysiology of the infertility in men with Down syndrome [28], [30], [31], [32]. However, it is clear that males with DS are generally infertile and have significant disruption of one or more levels of the hypothalamic-pituitary-gonadal axis resulting in elevated FSH and LH levels and inconsistent testosterone levels that are often in the low-normal range [28].…”

“…In fact, numerous published studies have yet to completely elucidate the pathophysiology of the infertility in men with Down syndrome [28], [30], [31], [32]. However, it is clear that males with DS are generally infertile and have significant disruption of one or more levels of the hypothalamic-pituitary-gonadal axis resulting in elevated FSH and LH levels and inconsistent testosterone levels that are often in the low-normal range [28]. Whatever the final cause of the hypogonadism and infertility in males with DS, our current understanding of endocrine regulation of bone turnover would suggest increased, not decreased bone turnover in both humans and mice.…”

Aneuploidy and Skeletal Health

“…In fact, the low bone mass phenotype was observed in a murine Down syndrome model (Ts65Dn) 8,35 , and was treatable with intermittent parathyroid hormone 8 . The decreased bone turnover in Down syndrome is an entirely unexpected result, given the hypogonadism and infertility apparent in both animals and humans with the disorder 52,53 . Although hypogonadism is a consistent finding in men with Down syndrome, 10,28,54 the pathophysiology of the infertility in men with Down syndrome remains unclear.…”

“…However, what is clear is that males with Down syndrome are generally infertile and have significant disruption of one or more levels of the hypothalamic-pituitary-gonadal axis resulting in elevated FSH and LH levels and inconsistent testosterone levels, that are frequently in the low-normal range 28,29,52 . Whatever the final cause of the hypogonadism and infertility in males, our current appreciation of the endocrine regulation of bone would favor significantly increased, not decreased bone turnover.…”