Repairing DNA double-strand breaks (DSBs) with homologous chromosomes as templates is the hallmark of meiosis. The critical outcome of meiotic homologous recombination is crossovers, which ensure faithful chromosome segregation and promote genetic diversity of progenies. Crossover patterns are tightly controlled and exhibit three characteristics: obligatory crossover, crossover interference, and crossover homeostasis. Aberrant crossover patterns are the leading cause of infertility, miscarriage, and congenital disease. Crossover recombination occurs in the context of meiotic chromosomes, and it is tightly integrated with and regulated by meiotic chromosome structure both locally and globally. Meiotic chromosomes are organized in a loop-axis architecture. Diverse evidence shows that chromosome axis length determines crossover frequency. Interestingly, short chromosomes show different crossover patterns compared to long chromosomes. A high frequency of human embryos are aneuploid, primarily derived from female meiosis errors. Dramatically increased aneuploidy in older women is the well-known "maternal age effect." However, a high frequency of aneuploidy also occurs in young women, derived from crossover maturation inefficiency in human females. In addition, frequency of human aneuploidy also shows other age-dependent alterations. Here, current advances in the understanding of these issues are reviewed, regulation of crossover patterns by meiotic chromosomes are discussed, and issues that remain to be investigated are suggested.
Cell Division/physiology* ; Chromosome Segregation/physiology* ; Humans ; Meiosis/genetics* ; Recombination, Genetic

Meiosis is an essential step in gametogenesis which is the key process in sexually reproducing organisms as meiotic aberrations may result in infertility. In meiosis, programmed DNA double-strand break (DSB) formation is one of the fundamental processes that are essential for maintaining homolog interactions and correcting segregation of chromosomes. Although the number and distribution of meiotic DSBs are tightly regulated, still abnormalities in DSB formation are known to cause meiotic arrest and infertility. This review is a detailed account of molecular bases of meiotic DSB formation, its evolutionary conservation, and variations in different species. We further reviewed the mutations of DSB formation genes in association with human infertility and also proposed the future directions and strategies about the study of meiotic DSB formation.
DNA Breaks, Double-Stranded ; DNA Repair/genetics* ; Humans ; Infertility/genetics* ; Meiosis/physiology*

Male meiosis is a complex process whereby spermatocytes undergo cell division to form haploid cells. This review focuses on the role of retinoic acid (RA) in meiosis, as well as several processes regulated by RA before cell entry into meiosis that are critical for proper meiotic entry and completion. Here, we discuss RA metabolism in the testis as well as the roles of stimulated by retinoic acid gene 8 (STRA8) and MEIOSIN, which are responsive to RA and are critical for meiosis. We assert that transcriptional regulation in the spermatogonia is critical for successful meiosis.
Animals ; Cell Differentiation/genetics* ; Humans ; Meiosis/drug effects* ; Spermatogenesis/physiology* ; Tretinoin/metabolism*

The synaptonemal complex (SC) is a meiosis-specific proteinaceous macromolecular structure that assembles between paired homologous chromosomes during meiosis in various eukaryotes. The SC has a highly conserved ultrastructure and plays critical roles in controlling multiple steps in meiotic recombination and crossover formation, ensuring accurate meiotic chromosome segregation. Recent studies in different organisms, facilitated by advances in super-resolution microscopy, have provided insights into the macromolecular structure of the SC, including the internal organization of the meiotic chromosome axis and SC central region, the regulatory pathways that control SC assembly and dynamics, and the biological functions exerted by the SC and its substructures. This review summarizes recent discoveries about how the SC is organized and regulated that help to explain the biological functions associated with this meiosis-specific structure.
Animals ; Chromosome Segregation ; Meiosis/physiology* ; Synaptonemal Complex/physiology*

Humans ; Meiosis/physiology* ; Mitosis/physiology*

Nanos2, a member of the Nanos2 gene family, is a specific gene in male germ cells and encodes an evolutionarily conserved RNA binding protein expressed in male primordial germ cells (PGCs) during the embryonic period as well as in the spermatogonial stem cells (SSCs) of the testis. In the embryonic period, Nanos2 promotes the development of male PGCs and inhibits them from meiosis. In the process of spermatogenesis, Nanos2 suppresses the differentiation of SSCs in the testis and maintains the stability of the SSC pool. The knockout of Nanos2 may cause the disappearance of germ cells and sterility in male mice while its overexpression in the testis may lead to accumulation of SSCs in seminiferous tubules. Besides, Nanos2 is involved in the degradation of specific RNAs and possibly associated with some diseases of the male reproductive system. This review focuses on the recent progress in the studies of Nanos2 in the male reproductive system.
Animals ; Cell Differentiation ; Gene Knockout Techniques ; Male ; Meiosis ; Mice ; RNA ; metabolism ; RNA-Binding Proteins ; genetics ; metabolism ; Spermatogenesis ; physiology ; Spermatogonia ; Spermatozoa ; Testis ; cytology

Adult ; Chromatids/genetics* ; Chromosome Aberrations ; Humans ; Infertility, Male/genetics* ; Male ; Meiosis ; Metaphase/genetics* ; Spermatocytes/physiology*

Spermatogenesis is a process consisting of spermatogonial proliferation, spermatocytic meiosis, and spermiogenesis, and is also considered to be a process in which heterochromatins gradually aggregate and finally reach a highly condensed formation in the sperm head. Recent studies show that epigenetic regulation plays a key role in spermatogenesis. This review discusses the mechanisms of epigenetic regulation in spermatogenesis in three aspects, DNA methylation, histone modification, and noncoding RNAs. These factors are essential for spermatogenesis, fertilization, and embryogenesis by mutual regulation as well as by gene expression regulation, transposon activation, sex chromosome inactivation, and genome imprinting.
DNA Methylation ; Embryonic Development ; Epigenesis, Genetic ; physiology ; Genomic Imprinting ; Humans ; Male ; Meiosis ; Spermatogenesis ; genetics ; Spermatogonia ; cytology ; physiology

Germ cells make two major decisions when they move from an indeterminate state to their final stage of gamete production. One decision is sexual commitment for sperm or egg production, and the other is to maintain mitotic division or entry into meiosis. It is unclear whether the two decisions are made as a single event or separate events, because there has been no evidence for the presence of germ cell sex prior to meiosis. Here we report direct evidence in the fish rainbow trout that gonia have distinct sexuality. We show that dazl expression occurs in both male and female gonia but exhibits differential intracellular distribution. More strikingly, we show that boule is highly expressed in male gonia but absent in female gonia. Therefore, mitotic gonia possess sex, sperm/egg decision and mitosis/meiosis decision are two independent events, and sperm/egg decision precedes mitosis/meiosis decision in rainbow trout, making this organism a unique vertebrate model for mechanistic understanding of germ cell sex differentiation and relationship between the two decisions.
Animals ; Female ; Fish Proteins ; genetics ; Gene Expression Regulation ; Male ; Meiosis ; Oncorhynchus mykiss ; genetics ; physiology ; Ovary ; cytology ; metabolism ; Ovum ; cytology ; metabolism ; RNA, Messenger ; genetics ; metabolism ; RNA-Binding Proteins ; genetics ; Sex Determination Processes ; Spermatozoa ; cytology ; metabolism ; Testis ; cytology ; metabolism

Stra8 (stimulated by retinoic acid gene 8) is a specific expression gene in mammalian germ cells' transition from mitosis to meiosis. Stra8 expresses in an anterior to posterior wave from embryonic days 12.5 to 16.5 in germ cells of XX gonads in mice. Meiosis germ cells are observed 1 day after Stra8 expression, which begins in the testis after birth and triggers meiosis entry. Germ cell sex determination is directed by a difference in the timing of entry into meiosis in embryonic gonads. The position of retinoic acid production and CYP26b1 expression that metabolizes RA to an inactive form regulates Stra8 expression. Although cytoplasmic protein Stra8 is necessary for the entry of germ cells into meiotic prophase, the function of the protein remains unknown.
Adaptor Proteins, Signal Transducing ; Animals ; Cytochrome P-450 Enzyme System ; metabolism ; Female ; Gene Expression ; Germ Cells ; cytology ; physiology ; Male ; Meiosis ; Mice ; Proteins ; genetics ; physiology ; Retinoic Acid 4-Hydroxylase ; Spermatogenesis ; genetics ; Tretinoin ; metabolism