PMID- 37471646
OWN - NLM
STAT- MEDLINE
DCOM- 20231023
LR  - 20231023
IS  - 1529-7268 (Electronic)
IS  - 0006-3363 (Print)
IS  - 0006-3363 (Linking)
VI  - 109
IP  - 4
DP  - 2023 Oct 13
TI  - Rhox8 homeobox gene ablation leads to rete testis abnormality and male 
      subfertility in micedagger.
PG  - 520-532
LID - 10.1093/biolre/ioad077 [doi]
AB  - The reproductive homeobox X-linked (Rhox) genes encode transcription factors that 
      are expressed selectively in reproductive tissues including the testis, 
      epididymis, ovary, and placenta. While many Rhox genes are expressed in germ 
      cells in the mouse testis, only Rhox8 is expressed exclusively in the Sertoli 
      cells during embryonic and postnatal development, suggesting a possible role of 
      Rhox8 in embryonic gonad development. Previously, Sertoli cell-specific knockdown 
      of RHOX8 resulted in male subfertility due to germ cell defects. However, this 
      knockdown model was limited in examining the functions of Rhox8 as RHOX8 
      knockdown occurred only postnatally, and there was still residual RHOX8 in the 
      testis. In this study, we generated new Rhox8 knockout (KO) mice using the 
      CRISPR/Cas9 system. Sex determination and fetal testis development were 
      apparently normal in mutant mice. Fertility analysis showed a low fecundity in 
      Rhox8 KO adult males, with disrupted spermatogenic cycles, increased germ cell 
      apoptosis, and reduced sperm count and motility. Interestingly, Rhox8 KO testes 
      showed an increase in testis size with dilated seminiferous tubules and rete 
      testis, which might be affected by efferent duct (ED) Rhox8 ablation 
      dysregulating the expression of metabolism and transport genes in the EDs. Taken 
      together, the data presented in this study suggest that Rhox8 in the Sertoli 
      cells is not essential for sex determination and embryonic testis differentiation 
      but has an important role in complete spermatogenesis and optimal male fertility.
CI  - Published by Oxford University Press on behalf of Society for the Study of 
      Reproduction 2023.
FAU - Oh, Yeongseok
AU  - Oh Y
AD  - Center for Reproductive Biology, School of Molecular Biosciences, College of 
      Veterinary Medicine, Washington State University, Pullman, Washington, USA.
AD  - Department of Physiology, Southern Illinois School of Medicine, Carbondale, IL, 
      USA.
FAU - Kasu, Maho
AU  - Kasu M
AD  - Center for Reproductive Biology, School of Molecular Biosciences, College of 
      Veterinary Medicine, Washington State University, Pullman, Washington, USA.
FAU - Bottoms, Constence J
AU  - Bottoms CJ
AD  - Center for Reproductive Biology, School of Molecular Biosciences, College of 
      Veterinary Medicine, Washington State University, Pullman, Washington, USA.
FAU - Douglas, Jenna C
AU  - Douglas JC
AD  - Center for Reproductive Biology, School of Molecular Biosciences, College of 
      Veterinary Medicine, Washington State University, Pullman, Washington, USA.
FAU - Sekulovski, Nikola
AU  - Sekulovski N
AD  - Department of Physiology, Southern Illinois School of Medicine, Carbondale, IL, 
      USA.
FAU - Hayashi, Kanako
AU  - Hayashi K
AD  - Center for Reproductive Biology, School of Molecular Biosciences, College of 
      Veterinary Medicine, Washington State University, Pullman, Washington, USA.
AD  - Department of Physiology, Southern Illinois School of Medicine, Carbondale, IL, 
      USA.
FAU - MacLean Ii, James A
AU  - MacLean Ii JA
AD  - Center for Reproductive Biology, School of Molecular Biosciences, College of 
      Veterinary Medicine, Washington State University, Pullman, Washington, USA.
AD  - Department of Physiology, Southern Illinois School of Medicine, Carbondale, IL, 
      USA.
LA  - eng
GR  - R01 HD093802/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
SB  - IM
MH  - Humans
MH  - Pregnancy
MH  - Female
MH  - Male
MH  - Mice
MH  - Animals
MH  - *Rete Testis/metabolism
MH  - Genes, Homeobox
MH  - Semen/metabolism
MH  - Testis/metabolism
MH  - *Infertility, Male/genetics/metabolism
MH  - Sertoli Cells/metabolism
MH  - Spermatogenesis/genetics
MH  - Mice, Knockout
PMC - PMC10577278
OTO - NOTNLM
OT  - Rhox8
OT  - Sertoli cells
OT  - efferent ducts
OT  - male fertility
OT  - reproductive homeobox X-linked gene
OT  - rete testis
OT  - spermatogenesis
COIS- The authors have declared that no conflict of interest exists.
EDAT- 2023/07/20 19:14
MHDA- 2023/10/23 00:44
PMCR- 2024/07/20
CRDT- 2023/07/20 15:43
PHST- 2023/02/23 00:00 [received]
PHST- 2023/07/10 00:00 [revised]
PHST- 2023/07/15 00:00 [accepted]
PHST- 2024/07/20 00:00 [pmc-release]
PHST- 2023/10/23 00:44 [medline]
PHST- 2023/07/20 19:14 [pubmed]
PHST- 2023/07/20 15:43 [entrez]
AID - 7227107 [pii]
AID - ioad077 [pii]
AID - 10.1093/biolre/ioad077 [doi]
PST - ppublish
SO  - Biol Reprod. 2023 Oct 13;109(4):520-532. doi: 10.1093/biolre/ioad077.