Pan Binyun, Chai Jin, Fei Kaixin, Zheng Ting, Jiang Yanzhi
Department of Zoology, College of Life Science, Sichuan Agricultural University, Ya'an, Sichuan, 625014, China.
State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, , Chengdu, Sichuan, 611130, China.
BMC Genomics. 2024 Dec 18;25(1):1193. doi: 10.1186/s12864-024-11122-3.
The ovary is a central organ in the reproductive system that produces oocytes and synthesizes and secretes steroid hormones. Healthy development and regular cyclical change in the ovary is crucial for regulating reproductive processes. However, the key genes and metabolites that regulate ovarian development and pregnancy have not been fully elucidated. This study conducted high-throughput RNA sequencing and untargeted metabolite profiling of the ovarian tissues from Chenghua pigs at four stages, including postnatal day 3 (D3), puberty at the age of about 125 days (Pub), sexual maturity at the age of about 365 days (Y1), and 105 days after pregnancy at the age of about 360 days (Pre).
A total of 9,264 and 1,593 differentially expressed genes (DEGs) were identified during ovarian development and pregnancy. Several key genes involved in ovarian development, including SQLE, HMGCS1, MSMO1, SCARB1, CYP11A1, HSD3B1, HSD17B1, and SERPINE1 were identified. Similarly, LUM, FN1, PLAUR, SELP, SDC1, and VCAN were considered to be associated with pregnancy maintenance. Overexpression of HSD17B1 in granulosa cells significantly upregulated estrogen synthesis-related genes (HSD3B1, CYP11A1, and STAR); meanwhile, overexpression of PLAUR promotes granulosa cell proliferation. Furthermore, 66, 24, 77, and 7 differentially expressed miRNAs (DEMis) were found, leading to the selection of key miRNAs such as ssc-miR-206, ssc-miR-107, ssc-miR-429, ssc-miR-210, and ssc-miR-133a-3p by differential miRNA-targeted mRNA interaction network; meanwhile, ssc-miR-133a-3p was validated to have a targeting relationship with KCNA1 by dual-luciferase reporter systems assay. At the metabolic levels, androstenedione, 17a-hydroxyprogesterone, dehydroepiandrosterone, and progesterone were identified, with their synthesis regulated by these DEGs in the ovarian steroidogenesis pathway. Furthermore, treatment of cells with androstenedione upregulated the expression of HSD3B1, CYP11A1, and STAR.
This study revealed the dynamic changes in the transcriptome and metabolome of pig ovaries across developmental stages and gestation, indicating that it may provide new theoretical insights for improving sow fertility.
卵巢是生殖系统的核心器官，可产生卵母细胞并合成和分泌甾体激素。卵巢的健康发育和周期性变化对于调节生殖过程至关重要。然而，调节卵巢发育和妊娠的关键基因和代谢物尚未完全阐明。本研究对成华猪四个阶段的卵巢组织进行了高通量RNA测序和非靶向代谢物谱分析，这四个阶段包括出生后第3天（D3）、约125日龄的青春期（Pub）、约365日龄的性成熟期（Y1）和约360日龄妊娠105天后（Pre）。
在卵巢发育和妊娠期间共鉴定出9264个和1593个差异表达基因（DEG）。鉴定出了几个参与卵巢发育的关键基因，包括SQLE、HMGCS1、MSMO1、SCARB1、CYP11A1、HSD3B1、HSD17B1和SERPINE1。同样，LUM、FN1、PLAUR、SELP、SDC1和VCAN被认为与维持妊娠有关。颗粒细胞中HSD17B1的过表达显著上调了雌激素合成相关基因（HSD3B1、CYP11A1和STAR）；同时，PLAUR的过表达促进颗粒细胞增殖。此外，还发现了66、24、77和7个差异表达的miRNA（DEMi），通过差异miRNA靶向mRNA相互作用网络筛选出了关键miRNA，如ssc-miR-206、ssc-miR-107、ssc-miR-429、ssc-miR-210和ssc-miR-133a-3p；同时，通过双荧光素酶报告系统测定验证了ssc-miR-133a-3p与KCNA1具有靶向关系。在代谢水平上，鉴定出了雄烯二酮、17α-羟孕酮、脱氢表雄酮和孕酮，它们的合成在卵巢类固醇生成途径中受这些DEG调节。此外，用雄烯二酮处理细胞上调了HSD3B1、CYP11A1和STAR的表达。
本研究揭示了猪卵巢在发育阶段和妊娠期转录组和代谢组的动态变化，表明其可能为提高母猪繁殖力提供新的理论见解。
