Pkd1 is required for male reproductive tract development

Abstract

Reproductive tract abnormalities and male infertility have higher incidence in autosomal dominant polycystic kidney disease (ADPKD) patients than in general population. In this work, we revealed that Pkd1, whose mutations account for 85% of ADPKD cases, is essential for male reproductive tract development. Disruption of Pkd1 caused a spectrum of defects in the murine male reproductive tract. The earliest visible defect in Pkd1-/- reproductive tract was cystic dilation of the efferent ducts, which are derivatives of the mesonephric tubules. Epididymis development was delayed or arrested in the Pkd1-/- mice. No sign of epididymal coiling was seen in the Pkd1 null mice. Disruption of Pkd1 in epithelia alone using the Pax2-cre mice was sufficient to cause efferent duct dilation and coiling defect in the epididymis, suggesting that Pkd1 is critical for epithelial development and maintenance in male reproductive tract. In-depth analysis showed that Pkd1 is required to maintain tubulin cytoskeleton and important for Tgf-β/Bmp signal transduction in the epithelia of male reproductive tract. Altogether, our results provide the first direct evidence for developmental roles of Pkd1 in male reproductive tract and provide new insights in reproductive tract abnormalities and infertility in ADPKD patients.

Novel roles of Pkd2 in male reproductive system development

“…As has been shown in previous studies, Pax2-cre specifically targets epithelia of the reproductive tract, but has no effect on mesenchyme and the testis (Nie and Arend, 2013). Therefore, using this model, we could exclude a potential effect from testis defects present in Pkd2 −/− mice.…”

“…This work demonstrates for the first time that Pkd2 , like Pkd1 (Nie and Arend, 2013), is essential for male reproductive system development. Disruption of Pkd2 in mice causes efferent duct dilation, lack of epididymal coiling, and altered testicular development.…”

“…Microtubule reduction also indicates that cilia might change in Pkd2 mutant epithelia. Overall, the reproductive tract phenotype of Pkd2 −/− mice is largely similar to that of Pkd1 −/− mice, suggesting that PC-2 and PC-1 may regulate common cellular activities during ductal system development of the male reproductive system (Nie and Arend, 2013). …”

“…In a previous study, we showed that the Pkd1 gene plays essential roles for male reproductive tract development (Nie and Arend, 2013). Here, we examined if Pkd2 , is also required for male reproductive system development.…”

GATA3 Is a Sensitive and Specific Marker of Benign and Malignant Mesonephric Lesions in the Lower Female Genital Tract

“…In a mouse model, Pkd1, a gene encoding polycystin1 (PC1), which is important for the structural integrity of many tissues and organs, is required for normal development of the reproductive tract. 70 Interestingly, in the absence of Pkd1 there was abnormal development of the efferent ductules (cranial mesonephros) and the epididymis (anterior mesonephros), but the seminal vesicles and ejaculatory ducts (caudal mesonephros) were not affected. On the basis of these findings, one could hypothesize that with mesonephric duct regression, in the absence of Mu¨llerian inhibiting substance, some phenotypic differences might be seen in the "cranial" remnants along the adnexa and more "caudal" remnants along the lateral wall of the uterus/ cervix (parametrial).…”