Distinct Prophase Arrest Mechanisms in Human Male Meiosis

Overview

Journal Development

Specialty Biology

Date 2018 Mar 16

PMID 29540502

Citations 11

Authors

Sabrina Z Jan

Aldo Jongejan

Cindy M Korver

Saskia K M van Daalen

Ans M M van Pelt

Sjoerd Repping

Geert Hamer

Affiliations

Soon will be listed here.

Abstract

To prevent chromosomal aberrations being transmitted to the offspring, strict meiotic checkpoints are in place to remove aberrant spermatocytes. However, in about 1% of males these checkpoints cause complete meiotic arrest leading to azoospermia and subsequent infertility. Here, we unravel two clearly distinct meiotic arrest mechanisms that occur during prophase of human male meiosis. Type I arrested spermatocytes display severe asynapsis of the homologous chromosomes, disturbed XY-body formation and increased expression of the Y chromosome-encoded gene and seem to activate a DNA damage pathway leading to induction of p63, possibly causing spermatocyte apoptosis. Type II arrested spermatocytes display normal chromosome synapsis, normal XY-body morphology and meiotic crossover formation but have a lowered expression of several cell cycle regulating genes and fail to silence the X chromosome-encoded gene Discovery and understanding of these meiotic arrest mechanisms increases our knowledge of how genomic stability is guarded during human germ cell development.

Citing Articles

Azoospermia/Oligozoospermia and Prostate Cancer Are Increased in Families of Women With Primary Ovarian Insufficiency.

Allen-Brady K, Kodama S, Verrilli L, Ramsay J, Johnstone E, Horns J J Endocr Soc. 2025; 9(4):bvaf030.

PMID: 40046104 PMC: 11879197. DOI: 10.1210/jendso/bvaf030.

Leydig cell metabolic disorder act as a new mechanism affecting for focal spermatogenesis in Klinefelter syndrome patients: a real world cross-sectional study base on the age.

Liu H, Zhang Z, Gao Y, Lin H, Zhu Z, Zheng H Front Endocrinol (Lausanne). 2023; 14:1266730.

PMID: 38027184 PMC: 10650597. DOI: 10.3389/fendo.2023.1266730.

X-linked RBBP7 mutation causes maturation arrest and testicular tumors.

Li J, Zheng H, Hou J, Chen J, Zhang F, Yang X J Clin Invest. 2023; 133(20).

PMID: 37843278 PMC: 10575721. DOI: 10.1172/JCI171541.

The First Analysis of Synaptonemal Complexes in Jawless Vertebrates: Chromosome Synapsis and Transcription Reactivation at Meiotic Prophase I in the Lamprey (Petromyzontiformes, Cyclostomata).

Matveevsky S, Tropin N, Kucheryavyy A, Kolomiets O Life (Basel). 2023; 13(2).

PMID: 36836858 PMC: 9959970. DOI: 10.3390/life13020501.

Mate-pair genome sequencing reveals structural variants for idiopathic male infertility.

Dong Z, Qian J, Law T, Chau M, Cao Y, Xue S Hum Genet. 2022; 142(3):363-377.

PMID: 36526900 DOI: 10.1007/s00439-022-02510-4.

References

Romanienko P, Camerini-Otero R . The mouse Spo11 gene is required for meiotic chromosome synapsis. Mol Cell. 2000; 6(5):975-87. DOI: 10.1016/s1097-2765(00)00097-6. View

de Rooij D, de Boer P . Specific arrests of spermatogenesis in genetically modified and mutant mice. Cytogenet Genome Res. 2004; 103(3-4):267-76. DOI: 10.1159/000076812. View

Wojtasz L, Daniel K, Roig I, Bolcun-Filas E, Xu H, Boonsanay V . Mouse HORMAD1 and HORMAD2, two conserved meiotic chromosomal proteins, are depleted from synapsed chromosome axes with the help of TRIP13 AAA-ATPase. PLoS Genet. 2009; 5(10):e1000702. PMC: 2758600. DOI: 10.1371/journal.pgen.1000702. View

Odorisio T, Rodriguez T, Evans E, Clarke A, Burgoyne P . The meiotic checkpoint monitoring synapsis eliminates spermatocytes via p53-independent apoptosis. Nat Genet. 1998; 18(3):257-61. DOI: 10.1038/ng0398-257. View

Daniel K, Lange J, Hached K, Fu J, Anastassiadis K, Roig I . Meiotic homologue alignment and its quality surveillance are controlled by mouse HORMAD1. Nat Cell Biol. 2011; 13(5):599-610. PMC: 3087846. DOI: 10.1038/ncb2213. View

Jan S, Vormer T, Jongejan A, Roling M, Silber S, de Rooij D . Unraveling transcriptome dynamics in human spermatogenesis. Development. 2017; 144(20):3659-3673. PMC: 5675447. DOI: 10.1242/dev.152413. View

Royo H, Polikiewicz G, Mahadevaiah S, Prosser H, Mitchell M, Bradley A . Evidence that meiotic sex chromosome inactivation is essential for male fertility. Curr Biol. 2010; 20(23):2117-23. DOI: 10.1016/j.cub.2010.11.010. View

Tsai M, Cheng Y, Lin T, Yang W, Lin Y . Clinical characteristics and reproductive outcomes in infertile men with testicular early and late maturation arrest. Urology. 2012; 80(4):826-32. DOI: 10.1016/j.urology.2012.06.054. View

Geng Y, Yu Q, Sicinska E, Das M, Schneider J, Bhattacharya S . Cyclin E ablation in the mouse. Cell. 2003; 114(4):431-43. DOI: 10.1016/s0092-8674(03)00645-7. View

10.

Vernet N, Mahadevaiah S, Yamauchi Y, Decarpentrie F, Mitchell M, Ward M . Mouse Y-linked Zfy1 and Zfy2 are expressed during the male-specific interphase between meiosis I and meiosis II and promote the 2nd meiotic division. PLoS Genet. 2014; 10(6):e1004444. PMC: 4072562. DOI: 10.1371/journal.pgen.1004444. View

11.

Barchi M, Mahadevaiah S, Di Giacomo M, Baudat F, de Rooij D, Burgoyne P . Surveillance of different recombination defects in mouse spermatocytes yields distinct responses despite elimination at an identical developmental stage. Mol Cell Biol. 2005; 25(16):7203-15. PMC: 1190256. DOI: 10.1128/MCB.25.16.7203-7215.2005. View

12.

Jan S, Hamer G, Repping S, de Rooij D, van Pelt A, Vormer T . Molecular control of rodent spermatogenesis. Biochim Biophys Acta. 2012; 1822(12):1838-50. DOI: 10.1016/j.bbadis.2012.02.008. View

13.

Yatsenko A, Georgiadis A, Ropke A, Berman A, Jaffe T, Olszewska M . X-linked TEX11 mutations, meiotic arrest, and azoospermia in infertile men. N Engl J Med. 2015; 372(22):2097-107. PMC: 4470617. DOI: 10.1056/NEJMoa1406192. View

14.

Baudat F, Manova K, Yuen J, Jasin M, Keeney S . Chromosome synapsis defects and sexually dimorphic meiotic progression in mice lacking Spo11. Mol Cell. 2000; 6(5):989-98. DOI: 10.1016/s1097-2765(00)00098-8. View

15.

Di Giacomo M, Barchi M, Baudat F, Edelmann W, Keeney S, Jasin M . Distinct DNA-damage-dependent and -independent responses drive the loss of oocytes in recombination-defective mouse mutants. Proc Natl Acad Sci U S A. 2005; 102(3):737-42. PMC: 545532. DOI: 10.1073/pnas.0406212102. View

16.

Yuan L, Liu J, Hoja M, Lightfoot D, Hoog C . The checkpoint monitoring chromosomal pairing in male meiotic cells is p53-independent. Cell Death Differ. 2001; 8(3):316-7. DOI: 10.1038/sj.cdd.4400828. View

17.

Liu D, Matzuk M, Sung W, Guo Q, Wang P, Wolgemuth D . Cyclin A1 is required for meiosis in the male mouse. Nat Genet. 1998; 20(4):377-80. DOI: 10.1038/3855. View

18.

Bolcun-Filas E, Rinaldi V, White M, Schimenti J . Reversal of female infertility by Chk2 ablation reveals the oocyte DNA damage checkpoint pathway. Science. 2014; 343(6170):533-6. PMC: 4048839. DOI: 10.1126/science.1247671. View

19.

Li X, Li X, Schimenti J . Mouse pachytene checkpoint 2 (trip13) is required for completing meiotic recombination but not synapsis. PLoS Genet. 2007; 3(8):e130. PMC: 1941754. DOI: 10.1371/journal.pgen.0030130. View

20.

Cheng Y, Kuo P, Teng Y, Kuo T, Chung C, Lin Y . Association of spermatogenic failure with decreased CDC25A expression in infertile men. Hum Reprod. 2006; 21(9):2346-52. DOI: 10.1093/humrep/del163. View