scholarly journals The effects of human umbilical cord mesenchymal stem cell transplantation on female fertility preservation in mice

2020 ◽  
Author(s):  
Qiwei Liu ◽  
Junhui Zhang ◽  
Yong Tang ◽  
Yuanyuan Ma ◽  
Zhigang Xue ◽  
...  

AbstractFemale fertility is the capacity to produce oocytes and achieve fertilization and pregnancy, and these outcomes are impaired by age, diseases, environment and social pressure. However, there is no effective therapy that preserves female reproductive ability. Mesenchymal stromal cells (MSCs) can exhibit multidirectional differentiation potential, and they have gained great attention as a tool for preserving female fertility. Therefore, this study uses human umbilical cords-MSCs (Huc-MSCs) to preserve and restore fertility in aging female mice and chemotherapy-damaged mice through the rescue of ovarian function and the reconstruction of the fallopian tubes and uterus. In our study, 2 mouse models were generated: aging mice (37 weeks old) and chemotherapy-damaged mice. Then, we injected Huc-MSCs into mice through the tail vein. After treatment, the effect of MSCs on the ovary, fallopian tubes and uterus was evaluated by analyzing gonadal hormone levels and by performing morphological analysis and statistical analysis. The levels of E2 and FSH exhibited a significant recovery after HUC-MSC transplantation both in aging mice and mice treated with chemotherapy. Huc-MSC treatment also increased the numbers of primordial, developing and preovulatory follicles in the ovaries of mice. Meanwhile, MSCs have been shown to rescue the morphology of the fallopian tubes and uterus through mechanisms such as regenerating the cilia in fallopian tubes and reforming glands and chorionic villi in the uterus. Therefore, it is suggested that Huc-MSCs may represent an effective potential treatment for preserving female fertility through recovery from chemotherapy damage and rescuing female reproductive organs from the effects of aging.

2021 ◽  
Vol 21 ◽  
Author(s):  
Qiwei Liu ◽  
Junhui Zhang ◽  
Yong Tang ◽  
Yuanyuan Ma ◽  
Zhigang Xue ◽  
...  

Background: Female fertility refers to the capacity to produce oocytes and achieve fertilization and pregnancy, and it is impaired by age, disease, environment and social pressure. However, no effective therapy that restores female reproductive ability has been established. Mesenchymal stromal cells (MSCs) exhibit multilineage differentiation potential and have attracted considerable attention as a tool for restoring female fertility. Methods: This study used human umbilical cord-MSCs (Huc-MSCs) to restore fertility in aging female mice and mice with chemotherapy-induced damage through the rescue of ovarian function and reconstruction of the fallopian tubes and uterus. In our study, two mouse models were generated: aging mice (35 weeks of age) and mice with chemotherapy-induced damage. Results: The effect of MSCs on the ovaries, fallopian tubes and uterus was evaluated by analyzing gonadal hormone levels and by performing morphological and statistical analyses. The levels of estradiol (E2) and follicle-stimulating hormone (FSH) exhibited significant recovery after Huc-MSC transplantation in both aging mice and chemotherapy-treated mice. Huc-MSC treatment also increased the number of primordial, developing and preovulatory follicles in the ovaries of mice. Moreover, MSCs were shown to rescue the morphology of the fallopian tubes and uterus through mechanisms such as cilia regeneration in the fallopian tubes and reformation of glands and endometrial tissue in the uterus. Conclusion: Huc-MSCs may represent an effective treatment for restoring female fertility through recovery from chemotherapy-induced damage and rescue of female reproductive organs from the effects of aging.


Author(s):  
Cristina Fabiani ◽  
Maria Giulia Ferrante ◽  
Caterina Meneghini ◽  
Emanuele Licata ◽  
Gemma Paciotti ◽  
...  

2017 ◽  
Vol 29 (7) ◽  
pp. 1426 ◽  
Author(s):  
K. A. Walters ◽  
M. C. Edwards ◽  
M. Jimenez ◽  
D. J. Handelsman ◽  
C. M. Allan

Androgens synergise with FSH in female reproduction but the nature of their interaction in ovarian function and fertility is not clear. In the present study, we investigated this interaction, notably whether higher endogenous FSH can overcome defective androgen actions in androgen receptor (AR)-knockout (ARKO) mice. We generated and investigated the reproductive function of mutant mice exhibiting AR resistance with or without expression of human transgenic FSH (Tg-FSH). On the background of inactivated AR signalling, which alone resulted in irregular oestrous cycles and reduced pups per litter, ovulation rates and antral follicle health, Tg-FSH expression restored follicle health, ovulation rates and litter size to wild-type levels. However, Tg-FSH was only able to partially rectify the abnormal oestrous cycles observed in ARKO females. Hence, elevated endogenous FSH rescued the intraovarian defects, and partially rescued the extraovarian defects due to androgen insensitivity. In addition, the observed increase in litter size in Tg-FSH females was not observed in the presence of AR signalling inactivation. In summary, the findings of the present study reveal that FSH can rescue impaired female fertility and ovarian function due to androgen insensitivity in female ARKO mice by maintaining follicle health and ovulation rates, and thereby optimal female fertility.


2015 ◽  
Vol 30 (7) ◽  
pp. 1625-1634 ◽  
Author(s):  
Ö. Baysal ◽  
L. Bastings ◽  
C.C.M. Beerendonk ◽  
S.A.E. Postma ◽  
J. IntHout ◽  
...  

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-19 ◽  
Author(s):  
Cadence E. Minge ◽  
Rebecca L. Robker ◽  
Robert J. Norman

Peroxisome proliferator-activated receptor gamma (PPARG) regulates cellular functions such as adipogenesis and immune cell activation. However, new information has indicated additional roles of PPARG directing the cyclic changes that occur within ovarian tissue of female mammals, including those that facilitate the release of oocytes each estrous cycle. In addition to ovarian PPARG expression and function, many PPARG actions within adipocytes and macrophages have additional direct and indirect implications for ovarian function and female fertility. This encompasses the regulation of lipid uptake and transport, insulin sensitivity, glucose metabolism, and the regulation of inflammatory mediator synthesis and release. This review discusses the developing links between PPARG activity and female reproductive function, and highlights several mechanisms that may facilitate such a relationship.


2015 ◽  
Vol 35 (6) ◽  
pp. 2383-2401 ◽  
Author(s):  
Xiaoqin Zhou ◽  
Jialu Gu ◽  
Yan Gu ◽  
Mulan He ◽  
Yang Bi ◽  
...  

Background: MSCs are a promising therapeutic resource. Paracrine effects and the induction of differentiation patterns are thought to represent the two primary mechanisms underlying the therapeutic effects of mesenchymal stem cell (MSC) transplantation in vivo. However, it is unclear which mechanism is involved in the therapeutic effects of human umbilical cord-derived MSC (hUC-MSC) transplantation. Methods and Results: Based on flow cytometry analysis, hUC-MSCs exhibited the morphological characteristics and surface markers of MSCs. Following directed neural induction, these cells displayed a neuron-like morphology and expressed high levels of neural markers. All types of hUC-MSCs, including differentiated and redifferentiated cells, promoted learning and memory function recovery in hypoxic-ischemic brain damaged (HIBD) rats. The hUC-MSCs secreted IL-8, which enhanced angiogenesis in the hippocampus via the JNK pathway. However, the differentiated and redifferentiated cells did not exert significantly greater therapeutic effects than the undifferentiated hUC-MSCs. Conclusion: hUC-MSCs display the biological properties and neural differentiation potential of MSCs and provide therapeutic advantages by secreting IL-8, which participates in angiogenesis in the rat HIBD model. These data suggest that hUC-MSC transplantation improves the recovery of neuronal function via an IL-8-mediated secretion mechanism, whereas differentiation pattern induction was limited.


2012 ◽  
Vol 27 (suppl 2) ◽  
pp. ii115-ii117 ◽  
Author(s):  
D. Meirow ◽  
H. Raanani ◽  
M. Brengauz ◽  
J. Dor ◽  
A. Tsafrir ◽  
...  

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