P–435 LH preserves oocyte-granulosa cell communication in mouse ovaries exposed to chemotherapy with alkylating agents

卵泡发生 卵母细胞 卵泡期 生物 男科 化疗 卵泡 内分泌学 内科学 窦卵泡 医学 胚胎 细胞生物学 胚胎发生
作者
L. Castillo,M J Soriano,José Antonio Martínez García,A Pellicer,Sonia Herraiz
出处
期刊:Human Reproduction [Oxford University Press]
卷期号:36 (Supplement_1)
标识
DOI:10.1093/humrep/deab130.434
摘要

Abstract Study question Does Luteinizing Hormone (LH) protect the follicular endowment and growth by improving oocyte-granulosa cell (GC) communication of follicles exposed to chemotherapy at the primordial stage? Summary answer LH treatment protects mouse primordial follicles against alkylating agents by preventing the chemotherapy-induced follicular depletion and the impairment of oocyte-GC communication during follicular growth. What is known already Impaired folliculogenesis is one of the most common deleterious side effects of alkylating agents in ovaries. Bidirectional communication between the oocyte and surrounding GCs is crucial for oocyte development. Therefore, defective gap junctions and reduced oocyte-derived factors compromise folliculogenesis, oocyte competence and meiotic maturation. Previous findings reported a significant LH protection of follicular viability and meiotic potential of MII oocytes exposed to chemotherapy at primordial stage. Therefore, we aimed to investigate the LH effects on cell junctions and communication between oocyte and GCs in growing follicles derived from quiescent oocytes exposed to alkylating chemotherapy. Study design, size, duration Adult 6-week-old CD1 female mice were allocated to control (n = 3), chemotherapy (ChT, n = 5) and ChT+LH (n = 5) groups. Chemotherapy (120 mg/Kg of cyclophosphamide and 12 mg/Kg of busulfan) was intraperitoneally administrated to ChT and ChT+LH mice. ChT+LH animals were pretreated with 1 IU of LH, followed by a second LH dose (1 IU) along with chemotherapy 24 hours later. Control mice only received vehicle (DMSO). Mice were euthanized 30 days later to collect ovaries. Participants/materials, setting, methods Follicles were mechanically isolated by puncture with 30-gauge needles from frozen-thawed half-ovaries. Isolated follicles measuring ≥100µm were selected to represent the secondary and later developmental stages. Part of them were kept intact while others were decumulated by using narrow pipettes to obtain denuded oocytes (DOs), and GCs. Follicles, ODs and GCs were analyzed by qRT-PCR to evaluate key factors in oocyte-GC junctions (Cx37, Cx43, Cdh1, Cdh2, Tjp1) and communication (Gdf9, Bmp15, Bmpr2, Alk4, Alk5, Alk6). Main results and the role of chance Chemotherapy induced a 2.1-fold reduction in the number of total isolated follicles (p = 0.036), reducing 2.7-fold the number of primordial and primary follicles (<100 µm; p = 0.034) and 1.9-fold the amount of growing follicles (≥100 µm; p = 0.036) compared to controls. LH-treated ovaries showed a 1.6-fold increase in the total follicle isolation yield when compared to ChT (p = 0.032), recovering control-like values (p=ns). This LH protection specially benefited the early-stage follicles (<100 µm), where a 1.9-fold increase in the number of isolated follicles was detected compared to ChT group (p = 0.016). Gene expression analysis of follicles (n = 168), DOs (n = 110) and GCs (from n = 153 follicles) revealed a global downregulation pattern in ChT samples for all genes, when compared to controls, with a significant fold change (FC) reduction for Gdf9 in follicles (FC: 0.36±0.16); Cx37, Cdh2 and Gdf9 in DOs (FC: 0.23±0.17, 0.09±0.03, and 0.17±0.07, respectively); and Cx37, Cx43, Gdf9 and Bmp15 in GCs (FC: 0.40±0.23, 0.17±0.07, 0.17±0.08, and 0.04±0.01, respectively). However, LH treated samples showed an overall improvement of gene expression pattern reaching control-like levels for all genes excepting for a downregulation of the Bmp15 expression in GC (FC: 0.28±0.24; p = 0.036). Limitations, reasons for caution Animal model study performed with a reduced sample size. Therefore, these findings should be validated in further studies with human tissue samples. Wider implications of the findings: Our findings suggest that LH treatment prevents the chemotherapy-induced follicle depletion. The LH protection of primordial population seems to preserve its ability to properly establish oocyte-GC interactions during growth and development, which is required to regulate follicular maturation and oocyte competence. Trial registration number Not applicable

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
文小杰完成签到,获得积分10
刚刚
山月完成签到,获得积分10
1秒前
CodeCraft应助研友_LOK59L采纳,获得10
1秒前
1秒前
2秒前
欣慰妙海完成签到 ,获得积分20
2秒前
CodeCraft应助zhaopeipei采纳,获得10
2秒前
LIUYONG发布了新的文献求助10
3秒前
lin发布了新的文献求助10
5秒前
6秒前
九湖夷上完成签到 ,获得积分10
6秒前
噼里啪啦完成签到 ,获得积分10
7秒前
大个应助hahaha123213123采纳,获得30
7秒前
7秒前
惊天大幂幂完成签到,获得积分10
7秒前
英姑应助Fang Xianxin采纳,获得10
8秒前
宋老师发布了新的文献求助30
8秒前
王洋完成签到,获得积分10
9秒前
lw777完成签到,获得积分20
9秒前
慢慢完成签到,获得积分10
9秒前
10秒前
靖123456发布了新的文献求助10
10秒前
拓跋箴完成签到,获得积分10
10秒前
彭于晏应助zy采纳,获得10
11秒前
精明玲完成签到 ,获得积分10
12秒前
12秒前
乐乐完成签到,获得积分10
13秒前
VirSnorlax完成签到,获得积分10
13秒前
SciGPT应助LL采纳,获得10
13秒前
妖孽宇发布了新的文献求助10
14秒前
aa完成签到,获得积分20
14秒前
aaaa完成签到,获得积分10
14秒前
马香芦完成签到,获得积分10
15秒前
西红柿完成签到,获得积分10
16秒前
17秒前
懵懂的冬灵完成签到,获得积分10
17秒前
碧蓝可仁完成签到 ,获得积分10
18秒前
王拉拉完成签到 ,获得积分10
18秒前
西西完成签到,获得积分10
18秒前
深情安青应助mkmimii采纳,获得10
19秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
Research on Disturbance Rejection Control Algorithm for Aerial Operation Robots 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038388
求助须知:如何正确求助?哪些是违规求助? 3576106
关于积分的说明 11374447
捐赠科研通 3305798
什么是DOI,文献DOI怎么找? 1819322
邀请新用户注册赠送积分活动 892672
科研通“疑难数据库(出版商)”最低求助积分说明 815029