Department of Obstetrics and Gynecology, Seoul National University Hospital, Daehak-ro 101, Jongno-gu, Seoul, 03080, South Korea.
Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University, Seoul, South Korea.
Reprod Sci. 2024 Jan;31(1):81-95. doi: 10.1007/s43032-023-01342-5. Epub 2023 Sep 14.
The decline in ovarian reserve and the aging of the ovaries is a significant concern for women, particularly in the context of delayed reproduction. However, there are ethical limitations and challenges associated with conducting long-term studies to understand and manipulate the mechanisms that regulate ovarian aging in human. The marmoset monkey offers several advantages as a reproductive model, including a shorter gestation period and similar reproductive physiology to that of human. Additionally, they have a relatively long lifespan compared to other mammals, making them suitable for long-term studies. In this study, we focused on analyzing the structural characteristics of the marmoset ovary and studying the mRNA expression of 244 genes associated with ovarian aging. We obtained ovaries from marmosets at three different reproductive stages: pre-pubertal (1.5 months), reproductive (82 months), and menopausal (106 months) ovaries. The structural analyses revealed the presence of numerous mitochondria and lipid droplets in the marmoset ovaries. Many of the genes expressed in the ovaries were involved in multicellular organism development and transcriptional regulation. Additionally, we identified the expression of protein-binding genes. Within the expressed genes, VEGFA and MMP9 were found to be critical for regulating ovarian reserve. An intriguing finding of the study was the strong correlation between genes associated with female infertility and genes related to fibrosis and wound healing. The authors suggest that this correlation might be a result of the repeated rupture and subsequent healing processes occurring in the ovary due to the menstrual cycle, potentially leading to the indirect onset of fibrosis. The expression profile of ovarian aging-related gene set in the marmoset monkey ovaries highlight the need for further studies to explore the relationship between fibrosis, wound healing, and ovarian aging.
卵巢储备功能下降和卵巢衰老,是女性面临的重大问题,尤其是在生育推迟的情况下。然而,由于存在伦理限制,对人类调节卵巢衰老的机制进行长期研究存在挑战。狨猴作为一种生殖模型具有几个优势,包括更短的妊娠期和与人类相似的生殖生理学。此外,与其他哺乳动物相比,它们的寿命相对较长,适合进行长期研究。在这项研究中,我们专注于分析狨猴卵巢的结构特征,并研究与卵巢衰老相关的 244 个基因的 mRNA 表达。我们从处于三个不同生殖阶段的狨猴中获得卵巢:青春期前(1.5 个月)、生殖期(82 个月)和绝经期(106 个月)。结构分析显示,狨猴卵巢中存在大量的线粒体和脂滴。许多在卵巢中表达的基因参与多细胞生物的发育和转录调控。此外,我们还鉴定了蛋白结合基因的表达。在所表达的基因中,VEGFA 和 MMP9 被发现对调节卵巢储备至关重要。该研究的一个有趣发现是,与女性不孕相关的基因与与纤维化和伤口愈合相关的基因之间存在强烈的相关性。作者认为,这种相关性可能是由于月经周期导致卵巢反复破裂和随后的愈合过程引起的,这可能导致纤维化的间接发生。狨猴卵巢中与卵巢衰老相关的基因集的表达谱突出表明,需要进一步研究探索纤维化、伤口愈合和卵巢衰老之间的关系。