Please wait a minute...
Journal of Integrative Agriculture
Advanced Online Publication | Current Issue | Archive | Adv Search
Construction of a goat placenta organoid culture system and its application in physiological and disease research
Ao Kang1*, Dong Wang1*, Jinglei Wang1, 2*, Mingjie Zhang1, Xue Niu1, Xiang Zhou1, Yajie Zhu1, Chao Qi2, Shuer Zhang2, Jiawen Zhang1, Feng Su1, 2# #br#

1 Shandong Provincial Key Laboratory of Zoonoses, Shandong Agricultural University, Taian 271018, China

2 Livestock and Poultry Genetic Resources Conservation and Biobreeding Engineering Center of Shandong Province, Livestock and Poultry Genetic Resources Gene Bank of Eastern Region in China, Jinan 250300, China

 Highlights 
1.This study first optimized an important system for goat placenta organoid construction
2.Goat placental organoids maintain the physiological characteristics of placental tissue
3.Goat placental organoids can be used for placental physiological and pathological research
Download:  PDF in ScienceDirect  
Export:  BibTeX | EndNote (RIS)      
摘要  

山羊作为一种重要的经济家畜,其繁殖效率受妊娠早期胎盘功能障碍的严重制约。山羊胎盘的健康对胎儿发育和产羔率至关重要,建立体外胎盘模型对于阐明其生理和病理特征十分必要。本研究旨在建立山羊胎盘滋养层类器官,并探索其在胎盘疾病中的应用。结果表明,妊娠80~90天的山羊胎盘滋养层组织(GPTT)具有高增殖活性,是构建类器官的理想来源。本实验在优化培养基中成功获得了山羊胎盘滋养层类器官(GPTOs),其呈现典型的囊状形态,并阳性表达滋养层标志物KRT23CK7E-cadherin以及干性因子SOX2。重要的是,这些类器官还表现出活跃的代谢和增殖能力。转录组分析显示,类器官的基因表达谱与体内组织高度相似,主要富集在激素响应、细胞黏附和妊娠相关通路。RT-PCR的结果表明类器官中关键胎盘滋养层基因(WNT5AVIMVILLINHBB)的表达与其在胎盘组织中一致。最后,利用山羊胎盘类器官构建的疾病模型表明,LPS刺激可诱导山羊胎盘滋养层类器官发生时间依赖性凋亡,这与体内感染所致的胎盘损伤类似。本研究首次在山羊中建立了具有生理和病理反应性的滋养层类器官模型,为反刍动物胎盘发育、母胎界面调控以及妊娠相关疾病研究提供了重要平台。



Abstract  

As an important economic livestock species, the reproductive efficiency of goats is greatly constrained by placental dysfunction during early pregnancy. The health of the goat placenta is crucial for fetal development and lambing rates. Establishing an in vitro placental model is necessary for elucidating its physiological and pathological characteristics. The purpose of this study is to establish goat placental trophoblast organoids and explore their application in placental diseases. Results indicate that goat placental trophoblast tissue (GPTT) from 80-90 d of gestation exhibits high proliferative activity, which is an ideal source for organoid construction. We successfully obtained goat placental trophoblast organoids in the optimized medium, which presented a typical cystic morphology and showed positive expression of trophoblast markers KRT23, CK7, E-cadherin, and the stemness factor SOX2. Importantly, these organoids also exhibit active metabolic and proliferative capabilities. Moreover, transcriptome analysis reveals that the gene expression profiles of the organoids are highly similar to those of in vivo tissues, and are mainly enriched in hormone response, cell adhesion, and pregnancy-related pathways. Notably, the expression of key placental trophoblast genes (WNT5A, VIM, VILL, INHBB) in the organoids is consistent with that in placental tissues. Finally, the disease model using goat placental organoids demonstrates that LPS stimulation induces time-dependent apoptosis in goat placental trophoblast organoids (GPTOs), which is analogous to placental damage caused by in vivo infection. This study firstly established a trophoblast organoid model in goats that has physiological and pathological responsibilities. Also providing an important platform for placental development research in ruminants, maternal-fetal interface regulation, and gestation-related diseases research.

Keywords:  goat placental trophoblast tissue       goat placental trophoblast organoids       transcriptome analysis       inflammation model  
Online: 08 June 2026  
Fund: 

This research was financially supported by grants from the National Key R&D Program of China (2021YFD1200902).

About author:  #Correspondence Feng Su, Email: Suf@sdau.edu.cn * All authors have equal contributions

Cite this article: 

Ao Kang, Dong Wang, Jinglei Wang, Mingjie Zhang, Xue Niu, Xiang Zhou, Yajie Zhu, Chao Qi, Shuer Zhang, Jiawen Zhang, Feng Su. 2026. Construction of a goat placenta organoid culture system and its application in physiological and disease research. Journal of Integrative Agriculture, Doi:10.1016/j.jia.2026.06.004

Ataei-Nazari S, Rahimi A, Bakhtiarizadeh M R, Jahandideh-Golroodbari P, Assadi-Alamouti A, Hajarizadeh A, Haji-Rahimi H, Mansouri-Bahrani B, Afshar-Bahrabad A, Ozturk I, Sharma M, Tvrdá E, & Mohammadi-Sangcheshmeh A. 2023. Alpha-linolenic acid alleviates the detrimental effects of lipopolysaccharide during in vitro ovine oocyte development. Theriogenology, 212, 64–72.

Alfian I, Chakraborty A, Yong H E, Saini S, Lau R W, Kalionis B, Dimitriadis E, Alfaidy N, Ricardo S D, Samuel C S. 2022. The placental NLRP3 inflammasome and its downstream targets, caspase-1 and interleukin-6, are increased in human fetal growth restriction: Implications for aberrant inflammation-induced trophoblast dysfunction. Cells, 11, 1413.

Bambra C, Tarara R. 1990. Immunohistochemical localization of chorionic gonadotrophin on baboon placenta, dispersed trophoblast cells and those derived from blastocysts grown in vitro. Reproduction, 88, 9–16.

Bello-Cabrera D, De La Cruz-Cruz L A, Larrondo C, Vázquez-García J M, Roldán-Santiago P. 2025. Effect of the administration of dexamethasone in pregnant goats: Vitality, thermography, physiological response, and behavioral patterns of newborn kids. Animal Reproduction Science, 279, 107949.

Chamseddine R S, Wahbeh F, Chervenak F, Salomon L J, Ahmed B, Rafii A. 2020. Pregnancy and neonatal outcomes in SARS‐CoV‐2 infection: a systematic review. Journal of pregnancy, 2020, 4592450.

Elizalde-Bielsa A, Muñoz P M, Zúñiga-Ripa A, Conde-Álvarez R. 2024. A Review on the Methodology and Use of the Pregnant Mouse Model in the Study of Brucella Reproductive Pathogenesis and Its Abortifacient Effect. Microorganisms, 12, 866.

Gridelet V, D'hauterive S P, Polese B, Foidart J M, Nisolle M, Geenen V. 2020. Human Chorionic Gonadotrophin: New Pleiotropic Functions for an "Old" Hormone During Pregnancy. Frontiers in Immunology, 11, 13.

Hohn H, Grümmer R, Boßerhoff S, Graf-Lingnau S, Reuss B, Bäcker C, Denker H. 1996. The role of matrix contact and of cell-cell interactions in choriocarcinoma cell differentiation. European journal of cell biology, 69, 76–85.

Horii M, Touma O, Bui T, Parast M M. 2020. Modeling human trophoblast, the placental epithelium at the maternal fetal interface. Reproduction, 160, R1–R11.

Hu Y, Geng Q, Wang L, Wang Y, Huang C, Fan Z, Kong D. 2024. Research progress and application of liver organoids for disease modeling and regenerative therapy. Journal of Molecular Medicine, 102, 859–874.

Kim D, Yoon Y-J, Choi D, Kim J, Lim J-Y. 2021. 3D organoid culture from adult salivary gland tissues as an ex vivo modeling of salivary gland morphogenesis. Frontiers in cell and developmental biology, 9, 698292.

Kong L-Z, Chandimali N, Han Y-H, Lee D-H, Kim J-S, Kim S-U, Kim T-D, Jeong D K, Sun H-N, Lee D S. 2019. Pathogenesis, early diagnosis, and therapeutic management of alcoholic liver disease. International Journal of Molecular Sciences, 20, 2712.

Lala P K, Nandi P. 2016. Mechanisms of trophoblast migration, endometrial angiogenesis in preeclampsia: The role of decorin. Cell adhesion & migration, 10, 111–125.

Lee B K, Kim J. 2021. Integrating High-Throughput Approaches and in vitro Human Trophoblast Models to Decipher Mechanisms Underlying Early Human Placenta Development. Frontiers in Cell and Developmental Biology, 9, 11.

Liu B Y, Ren S Q, An H, Liang Y X, Sheng X H, Qi X L, Xiao L F, Wang X G. 2024. Establishment of functional trophoblast organoids from trophoblast cells of bovine placenta. Cells & Development, 180, 7.

Liu X L, Wang G, Huang H Q, Lv X, Si Y R, Bai L X, Wang G H, Li Q H, Yang W W. 2023. Exploring maternal-fetal interface with in vitro placental and trophoblastic models. Frontiers in Cell and Developmental Biology, 11, 16.

Luconi M, Sogorb M A, Markert U R, Benfenati E, May T, Wolbank S, Roncaglioni A, Schmidt A, Straccia M, Tait S. 2022. Human-based new approach methodologies in developmental toxicity testing: a step ahead from the state of the art with a feto–placental organ-on-chip platform. International journal of environmental research and public health, 19, 15828.

Mao Q, Ye Q Y, Xu Y W, Jiang J W, Fan Y H, Zhuang L L, Liu G H, Wang T F, Zhang Z W, Feng T, Kong S B, Lu J H, Zhang H, Wang H P, Lin C P. 2023. Murine trophoblast organoids as a model for trophoblast development and CRISPR-Cas9 screening. Developmental Cell, 58, 25.

Michael A, Bayne J, Siepker C, Almeida M. 2025. Small ruminant reproductive loss investigation: a retrospective analysis and recommendations for optimizing diagnostic outcomes. Javma-Journal of the American Veterinary Medical Association, 263, S54–S64.

Nandi P, Lim H, Torres-Garcia E J, Lala P K. 2018. Human trophoblast stem cell self-renewal and differentiation: Role of decorin. Scientific Reports, 8, 8977.

Pan C, Zhaxi Y, Li H Y, Guan F, Pan J R, Wa D, Song T Z, Zhao W S. 2024. Effects of microbiota-testis interactions on the reproductive health of male ruminants: A review. Reproduction in Domestic Animals, 59, 10.

Papuchova H, Latos P A. 2022. Transcription factor networks in trophoblast development. Cellular and Molecular Life Sciences, 79, 17.

Peng L, Chelariu-Raicu A, Ye Y, Ma Z, Yang H, Ishikawa-Ankerhold H, Rahmeh M, Mahner S, Jeschke U, Von Schönfeldt V. 2021. Prostaglandin E2 receptor 4 (EP4) affects trophoblast functions via activating the cAMP-PKA-pCREB signaling pathway at the maternal-fetal interface in unexplained recurrent miscarriage. International Journal of Molecular Sciences, 22, 9134.

Reynaud D, Sergent F, Nahed R A, Traboulsi W, Collet C, Murthi P, Alfaidy N, Benharouga M. 2021. Evidence-Based View of Safety and Effectiveness of Prokineticin Receptors Antagonists during Pregnancy Prokineticin Receptors Antagonists during Pregnancy. Reproductive Sciences, 28, 178A–178A.

Rimland C A, Tilson S G, Morell C M, Tomaz R A, Lu W Y, Adams S E, Georgakopoulos N, Otaizo‐Carrasquero F, Myers T G, Ferdinand J R. 2021. Regional differences in human biliary tissues and corresponding in vitro–derived organoids. Hepatology, 73, 247–267.

Robertson S, Atkinson T, Friend M, Allworth M, Refshauge G. 2020. Reproductive performance in goats and causes of perinatal mortality: A review. Animal Production Science, 60, 1669–1680.

Roshan H M, Saadati D, Najimi M. 2018. Molecular detection of Brucella melitensis, Coxiella burnetii and Salmonella abortusovis in aborted fetuses of Baluchi sheep in Sistan region, south-eastern Iran. Iranian Journal of Veterinary Research, 19, 128–132.

Soares M J, Chapman B M, Kamei T, Yamamoto T. 1995. Control of trophoblast cell differentiation: lessons from the genetics of early pregnancy loss and trophoblast neoplasia. Development, growth & differentiation, 37, 355–364.

Syrett C M, Sierra I, Berry C L, Beiting D, Anguera M C. 2018. Sex-specific gene expression differences are evident in human embryonic stem cells and during in vitro differentiation of human placental progenitor cells. Stem Cells and Development, 27, 1360–1375.

Ullah R, Naz A, Akram H S, Ullah Z, Tariq M, Mithani A, Faisal A. 2020. Transcriptomic analysis reveals differential gene expression, alternative splicing, and novel exons during mouse trophoblast stem cell differentiation. Stem Cell Research & Therapy, 11, 17.

Vidal Jr M S, Radnaa E, Vora N, Khanipov K, Antich C, Ferrer M, Urrabaz-Garza R, Jacob J E, Menon R. 2024. Establishment and comparison of human term placenta–derived trophoblast cells. Biology of reproduction, 110, 950–970.

Wang Y Q, Guo Y Q, Wang P, Liu J Y, Zhang X, Liu Q, Wei L, Xu C, Qin J H. 2025. An engineered human placental organoid microphysiological system in a vascular niche to model viral infection. Communications Biology, 8, 15.

Wu H, Huang X-Y, Sun M-X, Wang Y, Zhou H-Y, Tian Y, He B, Li K, Li D-Y, Wu A-P. 2023. Zika virus targets human trophoblast stem cells and prevents syncytialization in placental trophoblast organoids. Nature Communications, 14, 5541.

Xu D L, Wang D, Zhou L S, Huang Z A, Sun M Z, Cao X X, Zhou J Y, Gao X X, He J N, Zhao J S, Li H G. 2025. DIA-based serum proteomics in goat pregnancy: biomarkers & mechanisms. Research in Veterinary Science, 193, 11.

Zgeib K.2025. Molecular Characterization of Dedifferentiation-Induced Oncogenic Stemness in the Intestinal Epithelium.

Zhao Y, Wang Q, Zhang W, Jia Q, Gao Q, Shuai L. 2023. Protocol to generate induced trophoblast stem cells from embryonic stem cells in mice. STAR protocols, 4, 102092.

[1] Huili Sun, Xinyue Wang, Qiuping Ren, Chunyan Liu, Xiaoqian Wang. The PuMYB93–PuGSTF12 regulatory module promotes anthocyanin accumulation in ‘Nanhong’ pear fruit[J]. >Journal of Integrative Agriculture, 2026, 25(2): 671-681.
[2] Xinyi Mao, Xuan Zhao, Zhi Luo, Ao He, Meng Yang, Mengjun Liu, Jin Zhao, Ping Liu. Transcriptome-based analysis of lignin accumulation in the regulation of fruit stone development and endocarp hardening in Chinese jujube[J]. >Journal of Integrative Agriculture, 2025, 24(6): 2217-2228.
[3] Yiying Li, Yuanyuan Hu, Bei Wang, Mengyao Lang, Shutang Zhou, Zhongxia Wu. Transcriptome-based analysis reveals chromatin remodeling in post-adult eclosion reconstruction of the insect fat body[J]. >Journal of Integrative Agriculture, 2025, 24(2): 668-679.
[4] Lijiao Ge, Weihao Miao, Kuolin Duan, Tong Sun, Xinyan Fang, Zhiyong Guan, Jiafu Jiang, Sumei Chen, Weimin Fang, Fadi Chen, Shuang Zhao. Comparative transcriptome analysis identifies key regulators of nitrogen use efficiency in chrysanthemum[J]. >Journal of Integrative Agriculture, 2025, 24(1): 176-195.
[5] Yuting Zhu, Yongli Wang, Yidong Wang, Guiping Zhao, Jie Wen, Huanxian Cui. Transcriptome analysis reveals steroid hormones biosynthesis pathway involved in abdominal fat deposition in broilers[J]. >Journal of Integrative Agriculture, 2024, 23(9): 3118-3128.
[6] WANG Xiao-dong, CAI Ying, PANG Cheng-ke, ZHAO Xiao-zhen, SHI Rui, LIU Hong-fang, CHEN Feng, ZHANG Wei, FU San-xiong, HU Mao-long, HUA Wei, ZHENG Ming, ZHANG Jie-fu. BnaSD.C3 is a novel major quantitative trait locus affecting semi-dwarf architecture in Brassica napus L.[J]. >Journal of Integrative Agriculture, 2023, 22(10): 2981-2992.
[7] LÜ Jing, Satyabrata NANDA, CHEN Shi-min, MEI Yang, HE Kang, QIU Bao-li, ZHANG You-jun, LI Fei, PAN Hui-peng.

A survey on the off-target effects of insecticidal double-stranded RNA targeting the Hvβ´COPI gene in the crop pest Henosepilachna vigintioctopunctata through RNA-seq [J]. >Journal of Integrative Agriculture, 2022, 21(9): 2665-2674.

[8] ZHOU Cheng-zhe, ZHU Chen, LI Xiao-zhen, CHEN Lan, XIE Si-yi, CHEN Guang-wu, ZHANG Huan, LAI Zhong-xiong, LIN Yu-ling, GUO Yu-qiong. Transcriptome and phytochemical analyses reveal roles of characteristic metabolites in the taste formation of white tea during withering process[J]. >Journal of Integrative Agriculture, 2022, 21(3): 862-877.
[9] CHENG Jin-tao, CHEN Hai-wen, DING Xiao-chen, SHEN Tai, PENG Zhao-wen, KONG Qiu-sheng, HUANG Yuan, BIE Zhi-long. Transcriptome analysis of the influence of CPPU application for fruit setting on melon volatile content[J]. >Journal of Integrative Agriculture, 2021, 20(12): 3199-3208.
[10] Aejaz Ahmad DAR, Susheel SHARMA, Reetika MAHAJAN, Muntazir MUSHTAQ, Ankila SALATHIA, Shahid AHAMAD, Jag Paul SHARMA. Overview of purple blotch disease and understanding its management through chemical, biological and genetic approaches[J]. >Journal of Integrative Agriculture, 2020, 19(12): 3013-3024.
[11] LIU Xuan, LIANG Wei, LI Yu-xing, LI Ming-jun, MA Bai-quan, LIU Chang-hai, MA Feng-wang, LI Cui-ying. Transcriptome analysis reveals the effects of alkali stress on root system architecture and endogenous hormones in apple rootstocks[J]. >Journal of Integrative Agriculture, 2019, 18(10): 2264-2271.
No Suggested Reading articles found!