PMID- 37594251
OWN - NLM
STAT- MEDLINE
DCOM- 20240214
LR  - 20240214
IS  - 2047-2927 (Electronic)
IS  - 2047-2919 (Linking)
VI  - 12
IP  - 3
DP  - 2024 Mar
TI  - Scrutinizing the human TEX genes in the context of human male infertility.
PG  - 570-584
LID - 10.1111/andr.13511 [doi]
AB  - BACKGROUND: Infertility affects around 15% of all couples worldwide and is 
      increasingly linked to variants in genes specifically expressed in the testis. 
      Well-established causes of male infertility include pathogenic variants in the 
      genes TEX11, TEX14, and TEX15, while few studies have recently reported variants 
      in TEX13B, TEX13C, FAM9A (TEX39A), and FAM9B (TEX39B). OBJECTIVES: We aimed at 
      screening for novel potential candidate genes among the human TEX ("testis 
      expressed") genes as well as verifying previously described disease associations 
      in this set of genes. MATERIALS AND METHODS: To this end, we screened the exome 
      sequencing data of 1305 men, including 1056 crypto- and azoospermic individuals, 
      and determined cell-specific expression by analyzing testis-specific single-cell 
      RNA sequencing data for genes with identified variants. To investigate the 
      overarching role in male fertility, we generated testis-specific knockdown (KD) 
      models of all 10 orthologous TEX genes in Drosophila melanogaster. RESULTS: We 
      detected rare potential disease-causing variants in TEX10, TEX13A, TEX13B, 
      TEX13C, TEX13D, ZFAND3 (TEX27), TEX33, FAM9A (TEX39A), and FAM9B (TEX39B), in 28 
      infertile men, of which 15 men carried variants in TEX10, TEX27, and TEX33. The 
      KD of TEX2, TEX9, TEX10, TEX13, ZFAND3 (TEX27), TEX28, TEX30, NFX1 (TEX42), 
      TEX261, and UTP4 (TEX292) in Drosophila resulted in normal fertility. DISCUSSION: 
      Based on our findings, the autosomal dominant predicted genes TEX10 and ZFAND3 
      (TEX27) and the autosomal recessive predicted gene TEX33, which all three are 
      conceivably required for germ cell maturation, were identified as novel potential 
      candidate genes for human non-obstructive azoospermia. We additionally identified 
      hemizygous loss-of-function (LoF) variants in TEX13B, TEX13C, and FAM9A (TEX39A) 
      as unlikely monogenic culprits of male infertility as LoF variants were also 
      found in control men. CONCLUSION: Our findings concerning the X-linked genes 
      TEX13B, TEX13C, and FAM9A (TEX39A) contradict previous reports and will decrease 
      false-positive reports in genetic diagnostics of azoospermic men.
CI  - (c) 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of 
      American Society of Andrology and European Academy of Andrology.
FAU - Sieper, Marie H
AU  - Sieper MH
AD  - Institute of Reproductive Genetics, University of Munster, Munster, Germany.
FAU - Gaikwad, Avinash S
AU  - Gaikwad AS
AD  - Institute of Reproductive Genetics, University of Munster, Munster, Germany.
FAU - Fros, Marion
AU  - Fros M
AD  - Institute of Reproductive Genetics, University of Munster, Munster, Germany.
FAU - Weber, Philipp
AU  - Weber P
AD  - Institute of Reproductive Genetics, University of Munster, Munster, Germany.
FAU - Di Persio, Sara
AU  - Di Persio S
AD  - Centre of Reproductive Medicine and Andrology, University Hospital Munster, 
      Munster, Germany.
FAU - Oud, Manon S
AU  - Oud MS
AUID- ORCID: 0000-0001-9513-3030
AD  - Department of Human Genetics, Donders Institute for Brain, Cognition and 
      Behaviour, Radboud University Medical Center, Nijmegen, Netherlands.
FAU - Kliesch, Sabine
AU  - Kliesch S
AUID- ORCID: 0000-0002-7561-4870
AD  - Centre of Reproductive Medicine and Andrology, University Hospital Munster, 
      Munster, Germany.
FAU - Neuhaus, Nina
AU  - Neuhaus N
AD  - Centre of Reproductive Medicine and Andrology, University Hospital Munster, 
      Munster, Germany.
FAU - Stallmeyer, Birgit
AU  - Stallmeyer B
AUID- ORCID: 0000-0003-2745-9965
AD  - Institute of Reproductive Genetics, University of Munster, Munster, Germany.
FAU - Tuttelmann, Frank
AU  - Tuttelmann F
AD  - Institute of Reproductive Genetics, University of Munster, Munster, Germany.
FAU - Wyrwoll, Margot J
AU  - Wyrwoll MJ
AD  - Institute of Reproductive Genetics, University of Munster, Munster, Germany.
LA  - eng
PT  - Journal Article
DEP - 20230818
PL  - England
TA  - Andrology
JT  - Andrology
JID - 101585129
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (TEX14 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (TEX10 protein, human)
RN  - 0 (Nuclear Proteins)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Male
MH  - *Azoospermia/genetics
MH  - Drosophila melanogaster
MH  - Cell Cycle Proteins/genetics
MH  - *Infertility, Male/metabolism
MH  - Testis/metabolism
MH  - Transcription Factors/metabolism
MH  - Nuclear Proteins/genetics
OTO - NOTNLM
OT  - TEX genes
OT  - TEX10
OT  - TEX13B
OT  - TEX27
OT  - TEX33
OT  - azoospermia
OT  - genetics
OT  - male infertility
EDAT- 2023/08/18 12:42
MHDA- 2024/02/14 12:47
CRDT- 2023/08/18 08:52
PHST- 2023/07/12 00:00 [revised]
PHST- 2023/03/06 00:00 [received]
PHST- 2023/08/06 00:00 [accepted]
PHST- 2024/02/14 12:47 [medline]
PHST- 2023/08/18 12:42 [pubmed]
PHST- 2023/08/18 08:52 [entrez]
AID - 10.1111/andr.13511 [doi]
PST - ppublish
SO  - Andrology. 2024 Mar;12(3):570-584. doi: 10.1111/andr.13511. Epub 2023 Aug 18.