Developmental Biology Division, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, Midlothian, UK.
Biol Reprod. 2019 Jul 1;101(1):112-125. doi: 10.1093/biolre/ioz068.
It is hypothesized that growth restriction occurs due to inadequate vascularization of the feto-maternal interface. Evidence exists for sexual dimorphism in placental function although associations between fetal sex and the endometrium remain poorly investigated. This study investigated the relationship between porcine fetal size, sex and endometrial angiogenesis at multiple gestational days (GD). Endometrial samples supplying the lightest and closest to mean litter weight (CTMLW), male and female Large White X Landrace conceptuses or fetuses were obtained at GD18, 30, 45, 60, and 90 (n = 5-9 litters/GD). Immunohistochemistry for CD31 revealed a greater number of blood vessels in endometrium supplying females compared to those supplying males at GD45. Endometrial samples supplying the lightest fetuses had fewer blood vessels (GD60) and uterine glands (GD90) compared to those supplying the CTMLW fetuses. Quantitative PCR revealed decreased CD31 (GD60), HPSE and VEGFA (GD90) expression, alongside increased HIF1A (GD45) expression in endometrial samples supplying the lightest compared to the CTMLW fetuses. At GD30, PTGFR, CD31, and VEGFA mRNA expression was increased in samples supplying female fetuses compared to those supplying male fetuses. Intriguingly, decreased expression of ACP5, CD31, HIF1A, and VEGFA mRNAs was observed at GD60 in endometrial samples supplying female fetuses compared to those supplying their male littermates. Endothelial cell branching assays demonstrated impaired endothelial cell branching in response to conditioned media from endometrial samples supplying the lightest and female fetuses compared with the CTMLW and male fetuses, respectively. This study has highlighted that endometrial tissues supplying the lightest and female fetuses have impaired angiogenesis when compared with the CTMLW and female fetuses respectively. Importantly, the relationship between fetal size, sex and endometrial vascularity is dynamic and dependent upon the GD investigated.
据推测，胎儿-母体界面的血管化不足会导致生长受限。尽管在胎盘功能方面存在性别二态性的证据，但胎儿性别与子宫内膜之间的关联仍未得到充分研究。本研究调查了多个妊娠期（GD）猪胎儿大小、性别和子宫内膜血管生成之间的关系。在 GD18、30、45、60 和 90 时，获得供应最轻和接近平均窝重（CTMLW）、雄性和雌性大白 X 长白胚胎或胎儿的子宫内膜样本（n=5-9 个窝/GD）。CD31 的免疫组织化学显示，在 GD45 时，供应雌性的子宫内膜中的血管数量多于供应雄性的子宫内膜。与供应 CTMLW 胎儿的子宫内膜样本相比，供应最轻胎儿的子宫内膜样本中的血管（GD60）和子宫腺（GD90）较少。定量 PCR 显示，与供应 CTMLW 胎儿的子宫内膜样本相比，供应最轻胎儿的子宫内膜样本中 CD31（GD60）、HPSE 和 VEGFA（GD90）的表达减少，HIF1A（GD45）的表达增加。在 GD30 时，与供应雄性胎儿的子宫内膜样本相比，供应雌性胎儿的子宫内膜样本中 PTGFR、CD31 和 VEGFA mRNA 的表达增加。有趣的是，与供应雄性胎儿的子宫内膜样本相比，供应雌性胎儿的子宫内膜样本中 ACP5、CD31、HIF1A 和 VEGFA mRNA 的表达在 GD60 时减少。内皮细胞分支测定表明，与供应 CTMLW 和雄性胎儿的子宫内膜样本相比，供应最轻和雌性胎儿的子宫内膜样本的内皮细胞分支受到抑制。本研究强调，与 CTMLW 和雌性胎儿相比，供应最轻和雌性胎儿的子宫内膜组织的血管生成受损。重要的是，胎儿大小、性别和子宫内膜血管之间的关系是动态的，取决于所研究的 GD。
