Research Institute of Human Morphology, Tsurupy st., 3, 117418 Moscow, Russia.
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova St. 32, 119991 Moscow, Russia.
Ann Anat. 2022 Feb;240:151880. doi: 10.1016/j.aanat.2021.151880. Epub 2021 Dec 9.
The sympathetic nervous system plays an important role in the regulation of pancreatic exocrine and endocrine secretion. The results of experimental studies also demonstrate the involvement of the sympathetic nervous system in the regulation of endocrine cell differentiation and islet formation during the development of the pancreas. However, the prenatal development of sympathetic innervation of the human pancreas has not yet been studied.
Pancreatic autopsy samples from 24 human fetuses were examined using immunohistochemistry with antibodies to tyrosine hydroxylase (TH). The density, concentration, and size (width, length, perimeter and area) of the TH-positive sympathetic nerves were compared in four developmental periods: pre-fetal (8-11 weeks post conception (w.p.c.), n = 6), early fetal (13-20 gestational weeks (g.w.), n = 7), middle fetal (21-28 g.w., n = 6) and late fetal (29-40 g.w., n = 5) using morphometric methods and statistical analysis (Multiple Comparisons p values). Double immunofluorescence with antibodies to TH and either insulin or glucagon and confocal microscopy were applied to analyze the interaction between the sympathetic nerves and endocrine cells, and the co-localization of TH with hormones.
TH-positive sympathetic nerves were detected in the fetal pancreas starting from the early stages (8 w.p.c.). The developmental dynamics of sympathetic nerves was follows: from the pre-fetal period, the amount of TH-positive nerves gradually increased and their branching occurred reaching the highest density and concentration in the middle fetal period, followed by a decrease in these parameters in the late fetal period. From the 14th g.w. onwards, thin TH-positive nerve fibers were mainly distributed in the vicinity of blood vessels and around the neurons of intrapancreatic ganglia, which is similar in adults. There were only rare TH-positive nerve fibers adjacent to acini or located at the periphery of some islets. The close interactions between the TH-positive nerve fibers and endocrine cells were observed in the neuro-insular complexes. Additionally, non-neuronal TH-containing cells were found in the pancreas of fetuses from the pre-fetal and early fetal periods. Some of these cells simultaneously contained glucagon.
The results demonstrate that sympathetic innervation of the human pancreas, including the formation of perivascular and intraganglionic nerve plexuses, extensively develops during prenatal period, while some processes, such as the formation of sympathetic innervation of islet capillaries, may occur postnatally. Non-neuronal TH-containing cells, as well as the interactions between the sympathetic terminals and endocrine cells observed in the fetal pancreas may be necessary for endocrine pancreas development in humans.
交感神经系统在调节胰腺外分泌和内分泌分泌中起着重要作用。实验研究的结果也表明，交感神经系统参与了胰腺发育过程中内分泌细胞分化和胰岛形成的调节。然而，人类胰腺交感神经的产前发育尚未得到研究。
使用酪氨酸羟化酶（TH）抗体对 24 个人类胎儿的胰腺尸检样本进行免疫组织化学检查。使用形态计量学方法和统计学分析（多重比较 p 值）比较了四个发育时期（前胎儿期[8-11 周妊娠（w.p.c.），n=6]、早期胎儿期[13-20 周妊娠（g.w.），n=7]、中期胎儿期[21-28 g.w.，n=6]和晚期胎儿期[29-40 g.w.，n=5]）TH 阳性交感神经的密度、浓度和大小（宽度、长度、周长和面积）。应用双免疫荧光技术，用 TH 抗体与胰岛素或胰高血糖素结合，并进行共聚焦显微镜分析，以分析交感神经与内分泌细胞之间的相互作用，以及 TH 与激素的共定位。
从早期（8 w.p.c.）开始，在胎儿胰腺中检测到 TH 阳性交感神经。交感神经的发育动态如下：从前胎儿期开始，TH 阳性神经的数量逐渐增加并发生分支，在中期达到最高密度和浓度，然后在晚期降低。从第 14 周妊娠开始，细的 TH 阳性神经纤维主要分布在血管附近和胰腺内神经节的神经元周围，与成人相似。只有少数 TH 阳性神经纤维紧邻腺泡或位于一些胰岛的外周。在神经胰岛复合物中观察到 TH 阳性神经纤维与内分泌细胞的密切相互作用。此外，在前胎儿期和早期胎儿期的胰腺中还发现了非神经元性含 TH 的细胞。其中一些细胞同时含有胰高血糖素。
结果表明，人类胰腺的交感神经支配包括血管周围和神经节内神经丛的形成，在前胎儿期广泛发育，而一些过程，如胰岛毛细血管的交感神经支配的形成，可能发生在出生后。在胎儿胰腺中观察到的非神经元性含 TH 的细胞以及交感神经末梢与内分泌细胞之间的相互作用，可能是人类内分泌胰腺发育所必需的。
