PMID- 33145986
OWN - NLM
STAT- MEDLINE
DCOM- 20211103
LR  - 20211103
IS  - 2047-2927 (Electronic)
IS  - 2047-2919 (Linking)
VI  - 9
IP  - 2
DP  - 2021 Mar
TI  - Homeobox transcription factor Meis1 is crucial to Sertoli cell mediated 
      regulation of male fertility.
PG  - 689-699
LID - 10.1111/andr.12941 [doi]
AB  - BACKGROUND: Infertility has become a global phenomenon and constantly declining 
      sperm count in males in modern world pose a major threat to procreation of 
      humans. Male fertility is critically dependent on proper functioning of 
      testicular Sertoli cells. Defective Sertoli cell proliferation and/or impaired 
      functional maturation may be one of the underlying causes of idiopathic male 
      infertility. Using high-throughput "omics" approach, we found binding sites for 
      homeobox transcription factor MEIS1 on the promoters of several genes 
      up-regulated in pubertal (mature) Sertoli cells, indicating that MEIS1 may 
      be crucial for Sertoli cell-mediated regulation of spermatogenesis at and after 
      puberty. OBJECTIVE: To decipher the role of transcription factor MEIS1 in Sertoli 
      cell maturation and spermatogenesis. MATERIALS AND METHODS: Sc-specific Meis1 
      knockdown (KD) transgenic mice were generated using pronuclear microinjection. 
      Morphometric and histological analysis of the testes from transgenic mice was 
      performed to identify defects in spermatogenesis. Epididymal sperm count and 
      litter size were analyzed to determine the effect of Meis1 knockdown on 
      fertility. RESULTS: Sertoli cell (Sc)-specific Meis1 KD led to massive germ cell 
      loss due to apoptosis and impaired spermatogenesis. Unlike normal pubertal Sc, 
      the levels of SOX9 in pubertal Sc of Meis1 KD were significantly high, like 
      immature Sc. A significant reduction in epididymal sperm count was observed in 
      these mice. The mice were found to be infertile or sub-fertile (with reduced 
      litter size), depending on the extent of Meis1 inhibition. DISCUSSION: The 
      results of this study demonstrated for the first time, a role of Meis1 in Sc 
      maturation and normal spermatogenic progression. Inhibition of Meis1 in Sc was 
      associated with deregulated spermatogenesis and a consequent decline in fertility 
      of the transgenic mice. CONCLUSIONS: Our results provided substantial evidence 
      that suboptimal Meis1 expression in Sc may be one of the underlying causes of 
      idiopathic infertility.
CI  - (c) 2020 American Society of Andrology and European Academy of Andrology.
FAU - Sarkar, Rajesh K
AU  - Sarkar RK
AD  - Cellular Endocrinology Lab, National Institute of Immunology, New Delhi, India.
AD  - Reproductive Physiology Lab, Department of Zoology, University of Delhi, New 
      Delhi, India.
FAU - Sen Sharma, Souvik
AU  - Sen Sharma S
AD  - Cellular Endocrinology Lab, National Institute of Immunology, New Delhi, India.
FAU - Mandal, Kamal
AU  - Mandal K
AD  - Cellular Endocrinology Lab, National Institute of Immunology, New Delhi, India.
FAU - Wadhwa, Neerja
AU  - Wadhwa N
AD  - Embryo Biotechnology Lab, National Institute of Immunology, New Delhi, India.
FAU - Kunj, Neetu
AU  - Kunj N
AD  - Embryo Biotechnology Lab, National Institute of Immunology, New Delhi, India.
FAU - Gupta, Alka
AU  - Gupta A
AD  - Cellular Endocrinology Lab, National Institute of Immunology, New Delhi, India.
FAU - Pal, Rahul
AU  - Pal R
AD  - Cellular Endocrinology Lab, National Institute of Immunology, New Delhi, India.
FAU - Rai, Umesh
AU  - Rai U
AD  - Reproductive Physiology Lab, Department of Zoology, University of Delhi, New 
      Delhi, India.
FAU - Majumdar, Subeer S
AU  - Majumdar SS
AUID- ORCID: 0000-0003-1724-7483
AD  - Cellular Endocrinology Lab, National Institute of Immunology, New Delhi, India.
AD  - National Institute of Animal Biotechnology, Hyderabad, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201123
PL  - England
TA  - Andrology
JT  - Andrology
JID - 101585129
RN  - 0 (Meis1 protein, mouse)
RN  - 0 (Myeloid Ecotropic Viral Integration Site 1 Protein)
SB  - IM
MH  - Animals
MH  - Fertility/genetics/*physiology
MH  - Gene Knockdown Techniques
MH  - Male
MH  - Mice, Transgenic
MH  - Myeloid Ecotropic Viral Integration Site 1 Protein/genetics/*physiology
MH  - Sertoli Cells/metabolism/*physiology
MH  - Spermatogenesis/genetics/physiology
OTO - NOTNLM
OT  - Meis1
OT  - germ cell apoptosis
OT  - knockdown
OT  - male fertility
OT  - sertoli cell
EDAT- 2020/11/05 06:00
MHDA- 2021/11/04 06:00
CRDT- 2020/11/04 05:56
PHST- 2020/06/25 00:00 [received]
PHST- 2020/10/27 00:00 [revised]
PHST- 2020/11/02 00:00 [accepted]
PHST- 2020/11/05 06:00 [pubmed]
PHST- 2021/11/04 06:00 [medline]
PHST- 2020/11/04 05:56 [entrez]
AID - 10.1111/andr.12941 [doi]
PST - ppublish
SO  - Andrology. 2021 Mar;9(2):689-699. doi: 10.1111/andr.12941. Epub 2020 Nov 23.