School of Agriculture and Food Science, University College Dublin, Belfield, Dublin, Ireland.
Division of Animal and Nutritional Sciences, West Virginia University, Morgantown, West Virginia, USA.
Biol Reprod. 2019 Feb 1;100(2):365-380. doi: 10.1093/biolre/ioy199.
This study investigated bovine conceptus-induced modifications to the endometrial transcriptome related to effects of interferon tau (IFNT), conceptus origin (in vivo vs. in vitro), and conceptus sex. In vitro (IVF) or in vivo (superovulation and artificial insemination, AI) produced blastocysts were transferred into recipient heifers on day 7 of the estrous cycle. On day 15, IVF- or AI-derived conceptuses were obtained by uterine flushing and individually placed on endometrial explants in media for 6 h. Explants were also cultured with media alone as a control or media containing 100 ng/mL IFNT. Total explant RNA was analyzed by RNA-Seq. Incubation of endometrium with IFNT or IVF- or AI-derived conceptuses changed (P ≤ 0.001) expression of 491, 498, and 576 transcripts, respectively, compared to the control. Further, 369 differentially expressed genes (DEGs) were common between explants exposed to IFNT or a conceptus. A total of 240 DEGs were uniquely altered by conceptuses (IVF- and AI-derived) but not IFNT. Of these transcripts, 46 were shared between the IVF and AI groups, while 61 and 133 were specific to IVF and AI conceptuses, respectively. Five genes [melanophilin (MLPH), prominin-2 (PROM2), myeloid associated differentiation marker (MYADM), vomeronasal 1 receptor 4 like (VN1R4L) and 5-hydroxytryptamine receptor 1A (HTR1A)] were more abundant in endometrium exposed to female compared to male conceptuses (P < 0.001). A single gene [ADP-ribosylation factor like GTPase 4C (ARL4C)] was more abundant in response to male conceptuses (P < 0.001) than female conceptuses. These data support the hypothesis that conceptus regulation of gene expression in the endometrium is complex and involves factors other than IFNT that may have a biological role in pregnancy establishment.
本研究调查了牛胚泡诱导的子宫内膜转录组变化,这些变化与干扰素 tau (IFNT)、胚泡来源(体内与体外)和胚泡性别有关。在发情周期的第 7 天,将体外受精 (IVF) 或体内受精 (超数排卵和人工授精,AI) 产生的囊胚转移到受体小母牛中。在第 15 天,通过子宫冲洗获得 IVF 或 AI 来源的胚泡,并将每个胚泡单独放置在培养基中的子宫内膜外植体上培养 6 小时。外植体也在单独含有培养基或含有 100ng/mL IFNT 的培养基中培养作为对照。通过 RNA-Seq 分析总外植体 RNA。与对照组相比,IFNT 或 IVF 或 AI 来源的胚泡孵育分别改变了 491、498 和 576 个转录本的表达(P ≤ 0.001)。此外,在暴露于 IFNT 或胚泡的外植体之间有 369 个差异表达基因 (DEG) 是共同的。共有 240 个 DEG 被胚泡(IVF 和 AI 来源)改变,但不受 IFNT 影响。这些转录物中,46 个在 IVF 和 AI 组之间共享,而 61 个和 133 个分别特异于 IVF 和 AI 胚泡。在暴露于雌性胚泡的子宫内膜中,有 5 个基因 [黑色素瘤相关蛋白(MLPH)、多潜能干细胞标记蛋白 2(PROM2)、髓样相关分化标记物(MYADM)、嗅鞘蛋白 1 受体 4 样(VN1R4L)和 5-羟色胺受体 1A(HTR1A)] 的丰度高于雄性胚泡(P < 0.001)。一个基因 [ADP-核糖基化因子样 GTP 酶 4C(ARL4C)] 在对雄性胚泡的反应中丰度高于雌性胚泡(P < 0.001)。这些数据支持这样的假设,即胚泡对子宫内膜中基因表达的调节是复杂的,涉及到除 IFNT 以外的其他因素,这些因素可能在妊娠建立中具有生物学作用。