The Center for the Study of Fetal Programming, Laramie, WY 82071, USA.
Reprod Biol Endocrinol. 2013 May 8;11:34. doi: 10.1186/1477-7827-11-34.
Previously we reported decreased circulating progesterone and fertility in one and two year old ewes born to undernourished mothers. This study was designed to investigate if this reduction in progesterone persisted into old age, and if it did, what mechanisms are involved.
Ewes were fed a nutrient restricted (NR, 50% of NRC recommendations) or control (C, 100% of NRC) diets from day 28 to 78 of gestation, then all were fed to requirements through parturition and weaning. Female offspring (4 per treatment group) were maintained as a group and fed to requirements from weaning until assigned to this study at 6 years of age. Ewes were synchronized for estrus (day 0) and blood samples were collected daily from day 0 to day 11 before necropsy on day 12. Blood serum and luteal tissue were assayed for progesterone concentrations by validated radioimmunoassay.
Circulation progesterone concentrations tended to be lower (P = 0.06) in NR than C offspring from day 0 to 11 of the estrous cycle. While total luteal weight was similar across groups, total progesterone content also tended to be reduced (P = 0.07) in luteal tissue of NR than C offspring. Activity of hepatic progesterone catabolizing enzymes and selected angiogenic factors in luteal tissue were similar between groups. Messenger RNA expression of steroidogenic enzymes StAR and P450scc were reduced (P < 0.05), while protein expression of StAR tended to be reduced (P < 0.07) and P450scc was reduced (P < 0.05) in luteal tissue of NR versus C offspring.
There appears to be no difference in hepatic steroid catabolism that could have led to the decreased serum progesterone. However, these data are consistent with the programming of decreased steroidogenic enzyme expression in CL of NR offspring, leading to reduced synthesis and secretion of progesterone.
我们之前曾报道过,营养不良的母羊所生的一岁和两岁的母羊循环中的孕酮和生育能力下降。本研究旨在调查孕酮的这种减少是否持续到老年,如果是这样,涉及哪些机制。
母羊从妊娠第 28 天到第 78 天接受限制营养(NR,NRC 建议的 50%)或对照(C,NRC 的 100%)饮食,然后在分娩和断奶期间都根据需要进行喂养。雌性后代(每组 4 只)作为一组饲养,从断奶开始一直饲养到 6 岁时进行本研究。母羊被同步发情(第 0 天),并在剖检前第 12 天的第 0 天至第 11 天每天采集血液样本。通过验证的放射免疫测定法测定血清和黄体组织中的孕酮浓度。
发情周期的第 0 天到第 11 天,NR 组的循环孕酮浓度趋于较低(P = 0.06)。尽管各组的总黄体重量相似,但 NR 组的黄体组织中的总孕酮含量也趋于降低(P = 0.07)。黄体组织中肝孕酮代谢酶和选定的血管生成因子的活性在各组之间相似。类固醇生成酶 StAR 和 P450scc 的信使 RNA 表达减少(P <0.05),而 StAR 的蛋白表达趋于减少(P <0.07),P450scc 的蛋白表达减少(P <0.05)在 NR 与 C 后代的黄体组织中。
肝类固醇代谢似乎没有差异,这可能导致血清孕酮减少。然而,这些数据与 NR 后代黄体中类固醇生成酶表达减少的编程一致,导致孕酮合成和分泌减少。