Gonadal mosaicism mediated female-biased gender control in mice

Bai, Meizhu; Liang, Dan; Cheng, Yan; Liu, Guolong; Wang, Qiudao; Li, Jinsong; Wu, Yuxuan

doi:10.1007/s13238-022-00910-w

Cited by 2 publications

(3 citation statements)

References 16 publications

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“…Gender ratio can be controlled by preselecting the sperm or the embryos. Using the former method for sex ratio control does not negatively influence the litter size [ 17 , 32 , 33 ]. Nevertheless, the later approach is known to decrease the litter size [ 15 , 16 ], which may not be compensated by superovulation, as observed in this study.…”

Section: Discussionmentioning

confidence: 99%

“…Male- or female-only offspring were produced by mating the father mice carrying a Y or X chromosome-linked Cas9 transgene with the mothers carrying an autosome-integrated sgRNA transgene, which targets the Topoisomerase 1 ( Top1 ) gene necessary for early embryonic survival [ 16 ]. A female-biased sex ratio shift was also observed in the progenies of male transgenic mice expressing a CRISPR/Cas9 system that cleaves the repetitive sequences on the Y chromosome [ 17 ]. These male transgenic mice produce only X sperm because their Y chromosome-bearing spermatogenic cells were eliminated during spermatogenesis by the CRISPR/Cas9 system targeting the Y chromosome.…”

Section: Introductionmentioning

confidence: 99%

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Knockout of Rlim Results in a Sex Ratio Shift toward Males but Superovulation Cannot Compensate for the Reduced Litter Size

Peng

Hou

et al. 2023

Animals

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Technologies that can preselect offspring gender hold great promise for improving farm animal productivity and preventing human sex-related hereditary diseases. The maternal Rlim allele is required for imprinted X-chromosome inactivation, which is essential for the normal development of female mouse embryos. In this study, we inactivated the maternal Rlim allele in embryos by crossing a male transgenic mouse line carrying an X-linked CMV-Cre transgene with a female line carrying a loxP-flanked Rlim gene. Knockout of the maternal Rlim gene in embryos resulted in a male-biased sex ratio skew in the offspring. However, it also reduced litter size, and this effect was not compensated for by superovulation in the mother mice. In addition, we showed that siRNA-mediated knockdown of Rlim in mouse embryos leads to the birth of male-only progenies. This study provides a new promising method for male-biased sex selection, which may help to improve the productivity in livestock and prevent sex-associated hereditary diseases in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Knockout of Rlim Results in a Sex Ratio Shift toward Males but Superovulation Cannot Compensate for the Reduced Litter Size

Peng

Hou

et al. 2023

Animals

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“…Douglas et al [ 15 ] employed a synthetic CRISPR-Cas9 approach to producing a single-sex litter, albeit with a 30–40% reduction in litter size, by the specific elimination of male or female mouse embryos. In 2022, Bai [ 16 ] expressed a CRISPR/Cas9 system during mouse spermatogenesis to target the Y chromosome in Y sperm, generating female-biased progenies. Although these gene-editing-based technologies are promising for gender control, their commercial viability is limited by ethical and biosafety concerns related to genetic modifications.…”

Section: Introductionmentioning

confidence: 99%

Gender Control of Mouse Embryos by Activation of TLR7/8 on X Sperm via Ligands dsRNA-40 and dsRNA-DR

Hou,

Peng,

Hong

et al. 2024

Molecules

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Gender control technologies are promising for enhancing the production efficiency of the farm animal industry, and preventing sex-linked hereditary diseases in humans. It has been shown that the X sperm of mammalian animals specifically expresses X-chromosome-derived toll-like receptor 7/8 (TLR7/8), and the activation of TLR7/8 on the X sperm by their agonist, R848, can separate X and Y sperm via the specific inhibition of X sperm motility. The use of R848-preselected sperm for fertilization resulted in sex-ratio-skewed embryos or offspring. In this study, we aimed to investigate whether two other TLR7/8 ligands, double-stranded RNA-40 (dsRNA-40) and double-stranded RNA-DR (dsRNA-DR), are also effective in the separation of mouse X and Y sperm and the subsequent generation of gender-ratio-skewed in vitro fertilization (IVF) embryos. Our results indicated that cholesterol modification significantly enhances the transfection of dsRNA-40 and dsRNA-DR into sperm cells. dsRNA-40 and dsRNA-DR incubation with mouse sperm could separate X and Y sperm by the specific suppression of X sperm motility by decreasing its ATP level and mitochondrial activity. The use of a dsRNA-40- or dsRNA-DR-preselected upper layer of sperm, which predominantly contains high-motility Y sperm, for IVF caused a male-biased sex ratio shift in resulting embryos (with 65.90–74.93% of embryos being male). This study develops a simple new method for the efficient separation of mammalian X and Y sperm, enabling the selective production of male or female progenies.

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Gonadal mosaicism mediated female-biased gender control in mice

Cited by 2 publications

References 16 publications

Knockout of Rlim Results in a Sex Ratio Shift toward Males but Superovulation Cannot Compensate for the Reduced Litter Size

Knockout of Rlim Results in a Sex Ratio Shift toward Males but Superovulation Cannot Compensate for the Reduced Litter Size

Gender Control of Mouse Embryos by Activation of TLR7/8 on X Sperm via Ligands dsRNA-40 and dsRNA-DR

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