Artificial ovaries constructed from biodegradable chitin-based hydrogels with the ability to restore ovarian endocrine function and alleviate osteoporosis in ovariectomized mice.
Artificial ovaries constructed from biodegradable chitin-based hydrogels with the ability to restore ovarian endocrine function and alleviate osteoporosis in ovariectomized mice.
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DOI：
10.1186/s12958-023-01092-8
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发表时间：
2023-05-19
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人工卵巢（AO）是为绝经后妇女提供生理激素的一种替代方法。使用藻酸盐（ALG）水凝胶构建的AO的治疗效果受到其低血管生成潜力、刚性和不可降解性的限制。为了解决这些限制，合成了促进细胞增殖和血管形成的可生物降解的基于几丁质（CTP）的水凝胶作为支持基质。在体外，从10-12日龄小鼠分离的卵泡在2D、ALG水凝胶和CTP水凝胶中培养。培养12天后，监测卵泡生长、类固醇激素水平、卵母细胞减数分裂能力和卵泡发生相关基因的表达。此外，将从10-12日龄小鼠分离的卵泡包封在CTP和ALG水凝胶中，并移植到卵巢切除（OVX）小鼠的腹膜袋中。移植后，每两周监测一次小鼠的类固醇激素水平、体重、直肠温度和内脏脂肪。在移植后6周和10周，收集子宫、阴道和股骨进行组织学检查。在体外培养条件下，卵泡在CTP水凝胶中正常发育。此外，卵泡直径和存活率，雌激素产生和卵泡发生相关基因的表达显着高于ALG水凝胶。移植1周后，CTP水凝胶中CD 34阳性血管数和Ki-67阳性细胞数均显著高于ALG水凝胶（P < 0.05），CTP水凝胶中卵泡恢复率（28%）显著高于ALG水凝胶（17.2%）（P < 0.05）。移植两周后，植入CTP移植物的OVX小鼠表现出正常的类固醇激素水平，并一直维持到第八周。移植10周后，CTP移植物有效地改善了OVX小鼠的骨丢失和生殖器官萎缩，并防止了体重和直肠温度的增加，这上级优于ALG移植物引起的那些。我们的研究首次证明CTP水凝胶在体外和体内支持卵泡的时间长于ALG水凝胶。结果突出了使用CTP水凝胶构建的AO在治疗更年期症状中的临床潜力。在线版本包含补充材料，可通过10.1186/s12958-023-01092-8获得。
Artificial ovary (AO) is an alternative approach to provide physiological hormone to post-menopausal women. The therapeutic effects of AO constructed using alginate (ALG) hydrogels are limited by their low angiogenic potential, rigidity, and non-degradability. To address these limitations, biodegradable chitin-based (CTP) hydrogels that promote cell proliferation and vascularization were synthesized, as supportive matrix. In vitro, follicles isolated from 10–12-days-old mice were cultured in 2D, ALG hydrogels, and CTP hydrogels. After 12 days of culture, follicle growth, steroid hormone levels, oocyte meiotic competence, and expression of folliculogenesis-related genes were monitored. Additionally, follicles isolated from 10–12-days-old mice were encapsulated in CTP and ALG hydrogels and transplanted into the peritoneal pockets of ovariectomised (OVX) mice. After transplantation, steroid hormone levels, body weight, rectal temperature, and visceral fat of the mice were monitored every two weeks. At 6 and 10 weeks after transplantation, the uterus, vagina, and femur were collected for histological examination. The follicles developed normally in CTP hydrogels under in vitro culture conditions. Additionally, follicular diametre and survival rate, oestrogen production, and expression of folliculogenesis-related genes were significantly higher than those in ALG hydrogels. After one week of transplantation, the numbers of CD34-positive vessels and Ki-67-positive cells in CTP hydrogels were significantly higher than those in ALG hydrogels (P < 0.05), and the follicle recovery rate was significantly higher in CTP hydrogels (28%) than in ALG hydrogels (17.2%) (P < 0.05). After two weeks of transplantation, OVX mice implanted with CTP grafts exhibited normal steroid hormone levels, which were maintained until week eight. After 10 weeks of transplantation, CTP grafts effectively ameliorated bone loss and atrophy of the reproductive organs, as well as prevented the increase in body weight and rectal temperature in OVX mice, which were superior to those elicited by ALG grafts. Our study is the first to demonstrate that CTP hydrogels support follicles longer than ALG hydrogels in vitro and in vivo. The results highlight the clinical potential of AO constructed using CTP hydrogels in the treatment of menopausal symptoms. The online version contains supplementary material available at 10.1186/s12958-023-01092-8.
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DOI：
10.18632/aging.202627
发表时间：
2021-02-26
期刊：
Aging
影响因子：
--
作者：
Huang J;Shan W;Li F;Wang Z;Cheng J;Lu F;Guo E;Beejadhursing R;Xiao R;Liu C;Yang B;Li X;Fu Y;Xi L;Wang S;Ma D;Chen G;Sun C
通讯作者：
Sun C
影响因子：
5.6
作者：
Lee, Sanghoon;Ryu, Ki-Jin;Kim, Tak
通讯作者：
Kim, Tak
影响因子：
14
作者：
Felder, Shani;Masasa, Hila;Cohen, Smadar
通讯作者：
Cohen, Smadar
影响因子：
6.1
作者：
Manavella, D. D.;Cacciottola, L.;Dolmans, M. M.
通讯作者：
Dolmans, M. M.
影响因子：
6.7
作者：
Luyckx, Valerie;Dolmans, Marie-Madeleine;Amorim, Christiani Andrade
通讯作者：
Amorim, Christiani Andrade