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青春期前狨猴睾丸异种移植的分化取决于小鼠宿主的性别和状态。

Differentiation of Testis Xenografts in the Prepubertal Marmoset Depends on the Sex and Status of the Mouse Host.

作者信息

Sharma Swati, Sandhowe-Klaverkamp Reinhild, Schlatt Stefan

机构信息

Center of Reproductive Medicine and Andrology, Institute of Reproductive and Regenerative Biology, Münster, Germany.

出版信息

Front Endocrinol (Lausanne). 2018 Aug 29;9:467. doi: 10.3389/fendo.2018.00467. eCollection 2018.

Abstract

This study investigates the effects of the endocrine milieu of immunodeficient mouse host (intact vs. castrated male, intact male vs. intact female) on prepubertal marmoset () testicular xenografts. Previous marmoset xenografting studies used castrated nude mouse hosts which did not support efficient graft survival and maturation. Due to the distinct endocrine milieu in marmosets with a deletion of exon 10 in the LH receptor, we wanted to explore whether the most efficient xenograft development occurs in intact male mouse hosts compared to intact females or castrated males. We xenografted freshly isolated tissue from prepubertal marmosets (age range 4-6 months) into the back skin of three groups of nude mice (intact male, castrated male, and intact female). We collected serum for endocrine determinations and grafts after 20 weeks and determined hormonal/reproductive status, graft survival, somatic cell development and initiation of germ cell differentiation. Graft development, tubular integrity, and germ cell differentiation status in the grafts retrieved from different hosts was scored by morphometric analysis. The influence of the different endocrine status was compared between groups of hosts. Endocrine readouts and histological endpoints in xenografts substantiate that grafts were exposed to different microenvironments and responded with host specific developmental patterns. The intact male hosts supported the most significant progression of germ cell development. Our data provide evidence for the important role of the host milieu on survival and differentiation of marmoset xenografts. The xenografting model offers innovative avenues to exploit development and endocrine effects in the primate marmoset testis using limited numbers of non-human primates for the experimental settings.

摘要

本研究调查了免疫缺陷小鼠宿主(完整雄性与去势雄性、完整雄性与完整雌性)的内分泌环境对青春期前狨猴睾丸异种移植的影响。以往的狨猴异种移植研究使用的是去势裸鼠宿主,其无法支持有效的移植物存活和成熟。由于狨猴中促黄体生成素受体第10外显子缺失导致内分泌环境不同,我们想探究与完整雌性或去势雄性相比,在完整雄性小鼠宿主中是否会出现最有效的异种移植发育。我们将青春期前狨猴(年龄范围4 - 6个月)新鲜分离的组织异种移植到三组裸鼠(完整雄性、去势雄性和完整雌性)的背部皮肤中。20周后,我们收集血清进行内分泌测定并获取移植物,测定激素/生殖状态、移植物存活、体细胞发育和生殖细胞分化的起始情况。通过形态计量分析对从不同宿主获取的移植物中的移植物发育、管状结构完整性和生殖细胞分化状态进行评分。比较不同宿主组之间不同内分泌状态的影响。异种移植中的内分泌读数和组织学终点证实移植物暴露于不同的微环境,并以宿主特异性的发育模式做出反应。完整雄性宿主支持生殖细胞发育的最显著进展。我们的数据为宿主微环境对狨猴异种移植存活和分化的重要作用提供了证据。异种移植模型为利用有限数量的非人类灵长类动物在实验环境中研究灵长类狨猴睾丸的发育和内分泌效应提供了创新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49af/6123353/399e81766f33/fendo-09-00467-g0001.jpg

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