Yaks (Bos grunniens) are one of the few livestock species uniquely adapted to harsh plateau environments, making them a sustainable and vital resource for high-altitude regions. They play a crucial role in supporting the livelihoods of herders by providing milk, meat, wool, and transportation. Yak-derived products, including butter, cheese, and meat, are indispensable in the diet of people living in remote mountainous areas where other livestock cannot thrive. Owing to the relatively low reproductive rate of yaks under natural conditions [[1], [2], [3]], assisted reproductive technologies (ART), such as in vitro fertilization (IVF), embryo transfer (ET), and in vitro maturation (IVM) have been developed and progressively applied to yak breeding [4,5]. Among these, IVM is effectively used in obtaining high-quality oocytes [6] and plays a critical role in implementing ART in the yak breeding industry. However, research on the mechanisms underlying yak oocyte maturation remains limited. Therefore, conducting further research on yak oocytes not only holds significant potential for advancing the development of the yak industry but also provides a valuable contribution to the comprehensive study of mammalian oocyte biology.

Oocyte maturation under in vitro conditions typically takes approximately 20–24 h, after which they become ready for fertilization [7]. Although IVM has been widely used in production practices [8], its clinical application remains restricted because of insufficient research in yak oocytes. Studies on yak oocytes have shown that supplementing the IVM system with growth factors such as 100 ng/mL epidermal growth factor (EGF) [9], 100 ng/mL insulin-like growth factor-1 (IGF-1) [10], and 5 ng/mL fibroblast growth factor 10 (FGF10) [11] improves their maturation rate. Additionally, low oxygen concentration, particularly 5 %, has shown positive effect on yak oocyte maturation in vitro [12]. However, these research findings remain insufficient to fully elucidate the mechanisms underlying yak oocyte maturation.

Numerous studies have highlighted the role of histone methylation, a fundamental epigenetic modification, in oocyte maturation [[13], [14], [15]]. Histone methylation plays a pivotal role in mammalian oocyte development [16]. Spatiotemporal regulation of histone methylation the expression of genes required for oocyte maturation and early embryonic development [6,16,17]. Among the various types of histone methylation, histone H3 trimethylation at lysine 36 (H3K36me3) and histone methyltransferase SET domain-containing 2 (SETD2), have garnered significant attention. SETD2 specifically catalyzes the conversion of H3K36me2 to H3K36me3 [18]. In mice, depletion of SETD2 significantly reduces trimethylation of H3K36, which affects oocyte meiotic progression [19]. Maternal depletion of SETD2 also leads to oocyte maturation defects and subsequent single-cell arrest post-fertilization [16]. While SETD2 regulates oocyte maturation, its impact on yak oocyte maturation remains to be elucidated.

In this study, we compared transcriptome changes between immature and mature yak oocytes and investigated the effect of SETD2 on oocyte maturation. We provided detailed insights into the yak oocyte maturation process and shed light on the mechanisms by which SETD2 regulates oocyte maturation.