Expression of ciliated bronchial epithelium 1 during human spermatogenesis

Fertil Steril. 2017 Jul;108(1):47-54. doi: 10.1016/j.fertnstert.2017.05.019. Epub 2017 Jun 7.

Abstract

Objective: To define the precise cellular localization of ciliated bronchial epithelium 1 (CBE1) in the human testis and test its relationship to impaired spermatogenesis.

Design: Gene expression analysis, and histologic and immunohistochemical evaluation.

Setting: University research laboratories and andrologic outpatient clinic.

Patient(s): Forty-three human testicular biopsies: 12 biopsies showing normal spermatogenesis (NSP), 8 with maturation arrest at level of spermatocytes (STA), 8 with maturation arrest at level of spermatids (SDA), 4 with scattered elongating spermatids, and 12 with Sertoli cell-only syndrome, with an additional 5 semen samples from healthy donors.

Intervention(s): None.

Main outcome measure(s): Evaluation of CBE1 expression in normal as well as impaired spermatogenesis on mRNA (quantitative reverse-transcription polymerase chain reaction and in situ hybridization) and protein level (immunohistochemistry, Western blot analysis).

Result(s): In normal spermatogenesis, CBE1 mRNA was expressed in late pachytene spermatocytes, and the protein was localized within the flagellum of elongating spermatids from stage V up to the spermiation in stage II. Immunoelectron microscopy showed CBE1 clearly associated with microtubules at the manchette, the head-tail coupling apparatus, and the flagellum, but the protein was absent in spermatozoa. Compared with normal spermatogenesis, CBE1 mRNA was statistically significantly reduced in samples with a maturation arrest at the level of round spermatids and primary spermatocytes, and was absent in samples showing Sertoli cell-only syndrome. CBE1 protein was completely missing in SDA samples showing few elongating spermatids.

Conclusion(s): Our data strongly suggest an influence of CBE1 in ciliogenesis in spermatids due to the localization at the microtubules of the elongating spermatids, indicating a role in the intramanchette and/or intraflagellar transport mechanism. The absence of CBE1 in spermatozoa suggests that CBE1 is important for the spermatid development but not for the maintenance of mature spermatozoa as a component of the flagellum.

Keywords: Intraflagellar transport; intramanchette transport; male fertility; microtubules; spermiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Developmental
  • Humans
  • Infertility, Male / metabolism*
  • Infertility, Male / pathology
  • Male
  • Nuclear Proteins / metabolism*
  • Organ Specificity / physiology
  • Spermatogenesis*
  • Spermatozoa / metabolism*
  • Spermatozoa / pathology
  • Testis / metabolism*
  • Testis / pathology
  • Tissue Distribution
  • Transcription Factors / metabolism*

Substances

  • C9orf24 protein, human
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Transcription Factors