Testis-specific knockout of Kdm2a reveals nonessential roles in male fertility but partially compromises spermatogenesis

Xiong, Xianrong; Huang, Xianli; Zhu, Yanjin; Hai, Zhuo; Fei, Xixi; Pan, Bangting; Yang, Qinhui; Xiong, Yan; Fu, Wei; Lan, Daoliang; Zhang, Xiaojian; Li, Jian

doi:10.1016/j.theriogenology.2023.06.008

Cited by 4 publications

(2 citation statements)

References 65 publications

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“…Interestingly, the Clock gene, which is a transcription activator, was highly expressed in the cerebellum, hypothalamus, and uterus in Small-tail Han sheep [36]. In addition, Lysine demethylase 2B (KDM2B) has been reported to play a role in spermatogenesis [37].…”

Section: Discussionmentioning

confidence: 99%

Distribution of Runs of Homozygosity and Their Relationship with Candidate Genes for Productivity in Kazakh Meat–Wool Sheep Breed

Amandykova,

Akhatayeva,

Kozhakhmet

et al. 2023

Genes

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Increasing the fertility of sheep remains one of the crucial issues of modern sheep breeding. The Kazakh meat–wool sheep is an excellent breed with high meat and wool productivity and well adapted to harsh conditions. Nowadays, runs of homozygosity (ROHs) are considered a suitable approach for studying the genetic characteristics of farm animals. The aims of the study were to analyze the distribution of ROHs, describe autozygosity, and detect genomic regions with high ROH islands. In this study, we genotyped a total of 281 Kazakh meat–wool sheep using the Illumina iScan® system (EquipNet, Canton, MA, USA) via Ovine SNP50 BeadChip array. As a results, a total of 15,069 ROHs were found in the three Kazakh meat–wool sheep populations. The mean number of ROH per animal across populations varied from 40.3 (POP1) to 42.2 (POP2) in the category 1+ Mb. Furthermore, the number of ROH per animal in ROH1–2 Mb were much higher than ROH2–4 Mb and ROH8–16 Mb in the three sheep populations. Most of individuals had small number of ROH>16 Mb. The highest and lowest genomic inbreeding coefficient values were observed in POP2 and POP3, respectively. The estimated FROH presented the impact that recent inbreeding has had in all sheep populations. Furthermore, a set of interesting candidate genes (BMP2, BMPR2, BMPRIB, CLOCK, KDM2B, TIAM1, TASP1, MYBPC1, MYOM1, and CACNA2D1), which are related to the productive traits, were found. Collectively, these findings will contribute to the breeding and conservation strategies of the Kazakh meat–wool sheep breed.

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Section: Discussionmentioning

confidence: 99%

Distribution of Runs of Homozygosity and Their Relationship with Candidate Genes for Productivity in Kazakh Meat–Wool Sheep Breed

Amandykova,

Akhatayeva,

Kozhakhmet

et al. 2023

Genes

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“…IHC was carried out according to previous protocols with minor modifications [32]. For IHC analysis, 4 µm sections were deparaffinized and rehydrated in a graded series of ethanol to water, followed by hydration with an ethanol gradient (100-70%) as described in our previous study [33].…”

Section: Immunohistochemical Stainingmentioning

confidence: 99%

The Expression and Epigenetic Characteristics of the HSF2 Gene in Cattle-Yak and the Correlation with Its Male Sterility

Yang,

Xie,

Pan

et al. 2024

Animals

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Aberrant expression of the heat shock proteins and factors was revealed to be closely associated with male reproduction. Heat shock factor 2 (HSF2) is a transcription factor that is involved in the regulation of diverse developmental pathways. However, the role and the corresponding molecular mechanism of HSF2 in male cattle-yak sterility are still poorly understood. Therefore, the aim of this study was to obtain the sequence and the biological information of the cattle-yak HSF2 gene and to investigate the spatiotemporal expression profiles of the locus during the development of cattle-yak testes. Additionally, the differential expression was analyzed between the cattle-yak and the yak, and the methylation of corresponding promoter regions was compared. Our results showed an additional 54 bp fragment and a missense mutation (lysine to glutamic acid) were presented in the cattle-yak HSF2 gene, which correlated with enriched expression in testicular tissue. In addition, the expression of the HSF2 gene showed dynamic changes during the growth of the testes, reaching a peak in adulthood. The IHC indicated that HSF2 protein was primarily located in spermatocytes (PS), spermatogonia (SP), and Sertoli cells (SC) in cattle-yak testes, compared with the corresponding cells of cattle and the yak. Furthermore, bisulfite-sequencing PCR (BSP) revealed that the methylated CpG sites in the promoter region of the cattle-yak HSF2 were more numerous than in the yak counterpart, which suggests hypermethylation of this region in the cattle-yak. Taken together, the low expression abundance and hypermethylation of HSF2 may underpin the obstruction of spermatogenesis, which leads to male cattle-yak infertility. Our study provided a basic guideline for the HSF2 gene in male reproduction and a new insight into the mechanisms of male cattle-yak sterility.

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Histone demethylase KDM2A recruits HCFC1 and E2F1 to orchestrate male germ cell meiotic entry and progression

Feng,

Gui,

Yin

et al. 2024

EMBO J

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In mammals, the transition from mitosis to meiosis facilitates the successful production of gametes. However, the regulatory mechanisms that control meiotic initiation remain unclear, particularly in the context of complex histone modifications. Herein, we show that KDM2A, acting as a lysine demethylase targeting H3K36me3 in male germ cells, plays an essential role in modulating meiotic entry and progression. Conditional deletion of Kdm2a in mouse pre-meiotic germ cells results in complete male sterility, with spermatogenesis ultimately arrested at the zygotene stage of meiosis. KDM2A deficiency disrupts H3K36me2/3 deposition in c-KIT+ germ cells, characterized by a reduction in H3K36me2 but a dramatic increase in H3K36me3. Furthermore, KDM2A recruits the transcription factor E2F1 and its co-factor HCFC1 to the promoters of key genes required for meiosis entry and progression, such as Stra8, Meiosin, Spo11, and Sycp1. Collectively, our study unveils an essential role for KDM2A in mediating H3K36me2/3 deposition and controlling the programmed gene expression necessary for the transition from mitosis to meiosis during spermatogenesis.

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Testis-specific knockout of Kdm2a reveals nonessential roles in male fertility but partially compromises spermatogenesis

Cited by 4 publications

References 65 publications

Distribution of Runs of Homozygosity and Their Relationship with Candidate Genes for Productivity in Kazakh Meat–Wool Sheep Breed

Distribution of Runs of Homozygosity and Their Relationship with Candidate Genes for Productivity in Kazakh Meat–Wool Sheep Breed

The Expression and Epigenetic Characteristics of the HSF2 Gene in Cattle-Yak and the Correlation with Its Male Sterility

Histone demethylase KDM2A recruits HCFC1 and E2F1 to orchestrate male germ cell meiotic entry and progression

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