Identification of SRY-box 30 as an age-related essential gatekeeper for male germ-cell meiosis and differentiation
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Identification of SRY-box 30 as an age-related essential gatekeeper for male germ-cell meiosis and differentiation. / Han, Fei; Yin, Li; Jiang, Xiao; Zhang, Xi; Zhang, Ning; Yang, Jun tang; Ouyang, Wei ming; Hao, Xiang lin; Liu, Wen bin; Huang, Yong sheng; Chen, Hong qiang; Gao, Fei; Li, Zhong tai; Guo, Qiao nan; Cao, Jia; Liu, Jin yi.
In: Aging Cell, Vol. 20, No. 5, e13343, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Identification of SRY-box 30 as an age-related essential gatekeeper for male germ-cell meiosis and differentiation
AU - Han, Fei
AU - Yin, Li
AU - Jiang, Xiao
AU - Zhang, Xi
AU - Zhang, Ning
AU - Yang, Jun tang
AU - Ouyang, Wei ming
AU - Hao, Xiang lin
AU - Liu, Wen bin
AU - Huang, Yong sheng
AU - Chen, Hong qiang
AU - Gao, Fei
AU - Li, Zhong tai
AU - Guo, Qiao nan
AU - Cao, Jia
AU - Liu, Jin yi
PY - 2021
Y1 - 2021
N2 - Although important factors governing the meiosis have been reported in the embryonic ovary, meiosis in postnatal testis remains poorly understood. Herein, we first report that SRY-box 30 (Sox30) is an age-related and essential regulator of meiosis in the postnatal testis. Sox30-null mice exhibited uniquely impaired testis, presenting the abnormal arrest of germ-cell differentiation and irregular Leydig cell proliferation. In aged Sox30-null mice, the observed testicular impairments were more severe. Furthermore, the germ-cell arrest occurred at the stage of meiotic zygotene spermatocytes, which is strongly associated with critical regulators of meiosis (such as Cyp26b1, Stra8 and Rec8) and sex differentiation (such as Rspo1, Foxl2, Sox9, Wnt4 and Ctnnb1). Mechanistically, Sox30 can activate Stra8 and Rec8, and inhibit Cyp26b1 and Ctnnb1 by direct binding to their promoters. A different Sox30 domain required for regulating the activity of these gene promoters, providing a “fail-safe” mechanism for Sox30 to facilitate germ-cell differentiation. Indeed, retinoic acid levels were reduced owing to increased degradation following the elevation of Cyp26b1 in Sox30-null testes. Re-expression of Sox30 in Sox30-null mice successfully restored germ-cell meiosis, differentiation and Leydig cell proliferation. Moreover, the restoration of actual fertility appeared to improve over time. Consistently, Rec8 and Stra8 were reactivated, and Cyp26b1 and Ctnnb1 were reinhibited in the restored testes. In summary, Sox30 is necessary, sufficient and age-associated for germ-cell meiosis and differentiation in testes by direct regulating critical regulators. This study advances our understanding of the regulation of germ-cell meiosis and differentiation in the postnatal testis.
AB - Although important factors governing the meiosis have been reported in the embryonic ovary, meiosis in postnatal testis remains poorly understood. Herein, we first report that SRY-box 30 (Sox30) is an age-related and essential regulator of meiosis in the postnatal testis. Sox30-null mice exhibited uniquely impaired testis, presenting the abnormal arrest of germ-cell differentiation and irregular Leydig cell proliferation. In aged Sox30-null mice, the observed testicular impairments were more severe. Furthermore, the germ-cell arrest occurred at the stage of meiotic zygotene spermatocytes, which is strongly associated with critical regulators of meiosis (such as Cyp26b1, Stra8 and Rec8) and sex differentiation (such as Rspo1, Foxl2, Sox9, Wnt4 and Ctnnb1). Mechanistically, Sox30 can activate Stra8 and Rec8, and inhibit Cyp26b1 and Ctnnb1 by direct binding to their promoters. A different Sox30 domain required for regulating the activity of these gene promoters, providing a “fail-safe” mechanism for Sox30 to facilitate germ-cell differentiation. Indeed, retinoic acid levels were reduced owing to increased degradation following the elevation of Cyp26b1 in Sox30-null testes. Re-expression of Sox30 in Sox30-null mice successfully restored germ-cell meiosis, differentiation and Leydig cell proliferation. Moreover, the restoration of actual fertility appeared to improve over time. Consistently, Rec8 and Stra8 were reactivated, and Cyp26b1 and Ctnnb1 were reinhibited in the restored testes. In summary, Sox30 is necessary, sufficient and age-associated for germ-cell meiosis and differentiation in testes by direct regulating critical regulators. This study advances our understanding of the regulation of germ-cell meiosis and differentiation in the postnatal testis.
KW - induced recovery
KW - meiosis arrest
KW - postnatal testis
KW - retinoic acid signalling
KW - SRY-box 30
KW - zygotene spermatocyte
U2 - 10.1111/acel.13343
DO - 10.1111/acel.13343
M3 - Journal article
C2 - 33721419
AN - SCOPUS:85102465488
VL - 20
JO - Aging Cell
JF - Aging Cell
SN - 1474-9718
IS - 5
M1 - e13343
ER -
ID: 259044650