Abstract
MAMLD1 has been implicated in testicular function in both human and mouse fetuses. Although three patients with MAMLD1 mutations were reported to have hypergonadotropic hypogonadism in their teens, the functional significance of MAMLD1 in the postnatal testis remains unclear. Here, we analyzed the phenotype of Mamld1 knockout (KO) male mice at reproductive ages. The reproductive organs of KO male mice were morphologically unremarkable, except for relatively small testes. Seminiferous tubule size and number of proliferating spermatogonia/spermatocytes were reduced in the KO testis. Daily sperm production of KO mice was mildly attenuated, whereas total sperm counts in epididymal semen remained normal. Sperm motility and morphology, as well as androgen levels in serum and testicular tissues and the number of pups born from cross-mated wildtype (WT) female mice, were comparable between WT and KO male mice. These results indicate that MAMLD1 contributes to the maintenance of postnatal testicular growth and daily sperm production but is dispensable for androgen biosynthesis and fertility. MAMLD1 likely plays supporting roles in multiple and continuous steps of male reproduction.
Highlights
MAMLD1 on the human X chromosome is a causative gene for hypospadias [1]
The present study demonstrated that Mamld1 deficiency produces small testes in mice at reproductive ages
The number of proliferating cell nuclear antigen (PCNA)-positive cells in the seminiferous tubules and daily sperm production was reduced in Mamld1 KO mice
Summary
MAMLD1 on the human X chromosome is a causative gene for hypospadias [1]. MAMLD1 mutations, which are presumed to affect androgen biosynthesis in the fetal testis, result in hypospadias. Fujisawa et al performed a long-term follow-up study of three patients with hypospadias due to MAMLD1 nonsense mutations [8]. Two of the three patients presented with testicular microlithiasis [8], an ultrasound finding often associated with testicular dysfunction [9] These results suggest that MAMLD1 is involved in postnatal testicular function. The abovementioned notion is based on data from only three patients and needs to be validated in further studies In this regard, previous studies have shown that Mamld KO male mice are fertile [3,10], detailed testicular function has yet to be studied in these adult mice. The aim of this study was to clarify the phenotype of Mamld KO male mice at reproductive ages
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