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Nicotinamide boosts oocyte quantity and quality by promoting N4-acetylation modification in lupus mice
Yun Xie1,2,3, Chuanchuan Zhou1,2,3, Qi Guo1,2,3
1Reproductive Medicine Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, China.
Abstract:
Patients with systemic lupus erythematosus (SLE) often have decreased fertility. Gene translation is crucial to oocyte meiosis and development. However, it remains unclear how SLE affects this process. Here, we used single-cell transcriptome and translatome sequencing to uncover a notable disruption in protein translation in oocytes from SLE mice, associated with the N4-acetylcytidine (ac4C) modification. Inhibition of ac4C levels in vitro substantially reduced oocyte translation efficiency. Notably, through trace-cell ac4C-RNA immunoprecipitation (acRIP) sequencing, we mapped the ac4C landscape in SLE mouse oocytes and found that deficient ac4C modification substantially impaired the translation of Zygote arrest 1. Furthermore, we demonstrated that nicotinamide treatment notably and safely improved the quantity and quality of oocytes in SLE mice by enhancing ac4C modification levels. Our findings highlight the essential role of N- acetyltransferase 10 (NAT10)-mediated ac4C modification in abnormal oocyte development in SLE and suggest that nicotinamide holds promise for improving fertility in patients with SLE.
Insights
Systemic lupus erythematosus (SLE) disrupts oocyte development by impairing protein translation linked to N4-acetylcytidine (ac4C) modification. Nicotinamide treatment safely enhances ac4C levels, improving oocyte quality and quantity in SLE mice.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Immunology
Background:
- Systemic lupus erythematosus (SLE) is associated with reduced fertility in patients.
- Oocyte development and meiosis rely heavily on precise gene translation.
- The impact of SLE on oocyte gene translation remains largely unknown.
Purpose of the Study:
- To investigate the effects of SLE on gene translation in oocytes.
- To identify molecular mechanisms underlying SLE-induced oocyte dysfunction.
- To explore potential therapeutic strategies for improving fertility in SLE.
Main Methods:
- Single-cell transcriptome and translatome sequencing in SLE mouse models.
- In vitro experiments assessing the role of N4-acetylcytidine (ac4C) modification.
- Trace-cell ac4C-RNA immunoprecipitation (acRIP) sequencing.
- Assessment of nicotinamide treatment effects on oocyte quantity and quality.
Main Results:
- SLE significantly disrupts protein translation in oocytes, linked to ac4C modification.
- Reduced ac4C levels impair oocyte translation efficiency, notably affecting Zygote arrest 1.
- Nicotinamide treatment enhanced ac4C levels, improving oocyte quantity and quality in SLE mice.
- N-acetyltransferase 10 (NAT10) plays a key role in ac4C-mediated oocyte development.
Conclusions:
- ac4C modification is crucial for normal oocyte development in the context of SLE.
- Dysfunctional ac4C modification contributes to impaired oocyte quality in SLE.
- Nicotinamide shows promise as a safe therapeutic agent to improve fertility in SLE patients.
