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Meiosis II entails cell division and segregation of the sister chromatids, resulting in the production of four unique haploid gametes. The steps for meiosis II are similar to mitosis, except that meiosis II occurs in haploid cells, whereas mitosis occurs in diploid cells.
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Meiosis II is the second and final stage of meiosis. It relies on the haploid cells produced during meiosis I, each of which contain only 23 chromosomes—one from each homologous initial pair. Importantly, each chromosome in these cells is composed of two joined copies, and when these cells enter meiosis II, the goal is to separate such sister chromatids using the same microtubule-based network employed in other division processes. The result of meiosis II is two haploid cells, each...
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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
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PCID2 is essential for spermatogonial differentiation by regulating alternative splicing.

Feiyin Zhu1,2,3, Ying Zhang1,2, Yu Xi1,4

  • 1Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.

Cellular and Molecular Life Sciences : CMLS
|January 12, 2026
PubMed
Summary

PCI domain-containing protein 2 (PCID2) is crucial for male fertility. Knockout mice show infertility due to impaired spermatogenesis, highlighting PCID2

Keywords:
Alternative splicingMale infertilityPCID2SpermatogenesisSpermatogonial differentiation

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Area of Science:

  • Reproductive Biology
  • Molecular Biology
  • Genetics

Background:

  • Spermatogenesis involves complex transcriptional regulation.
  • PCI domain-containing protein 2 (PCID2) is part of the transcription-export complex 2 (TREX-2) and involved in RNA processing.
  • The specific role of PCID2 in spermatogenesis is not well understood.

Purpose of the Study:

  • To investigate the physiological functions of PCID2 in spermatogenesis and male fertility.
  • To elucidate the molecular mechanisms by which PCID2 influences germ cell development.

Main Methods:

  • Generation of germline conditional knockout (Pcid2-SKO) mice using Stra8-Cre.
  • Single-cell transcriptome analysis to identify developmental defects.
  • Gene Set Enrichment Analysis (GSEA) to analyze pathway enrichment.
  • Immunoprecipitation-Mass Spectrometry (IP-MS) and Co-immunoprecipitation (Co-IP) to identify interacting proteins.
  • RNA sequencing and PCR to identify PCID2 splicing targets.

Main Results:

  • Pcid2-SKO mice are infertile with extensive germ cell apoptosis, impaired spermatogonial differentiation, and failed meiosis initiation.
  • Single-cell analysis revealed developmental arrest at the spermatogonia transition stage.
  • PCID2 deficiency significantly decreased mRNA splicing pathway enrichment in germ cells.
  • PCID2 interacts with SNRPG, hnRNPH1, and SF3B1, modulating alternative splicing.
  • Four key genes (Prpf3, Nek3, Dvl2, Slc30a9) were identified as PCID2 splicing targets.

Conclusions:

  • PCID2 is essential for normal spermatogenesis and male fertility.
  • PCID2 regulates alternative splicing (AS) of critical genes involved in cell cycle progression, spliceosome assembly, and mitochondrial homeostasis.
  • This study reveals novel molecular mechanisms of spermatogenesis and emphasizes the importance of AS in germ cell development.