Journal of Assisted Reproduction and Genetics

, Volume 34, Issue 4, pp 535–545 | Cite as

Long-term effects of repeated superovulation on the uterus and mammary gland in rhesus monkeys

  • Peipei Yan
  • Jingyi Xu
  • Yan Zeng
  • Guoying Dong
  • Huarong Cao
  • Meimei Zheng
  • Hui Zhu
Reproductive Physiology and Disease



The aim of this study is to evaluate the effect of repeated controlled ovarian hyperstimulation (COH) on the structure and function of the uterus and mammary gland.


Three adult female rhesus monkeys were superovulated up to four times, and three spontaneously ovulating monkeys were used as controls. After a 5-year period, the uterus and mammary gland tissue samples were collected for examination of their structure and function. Further, the expression of certain tumor markers was examined to assess the cancer risk for each organ.


Expression of Wnt7a (associated with the functional/developmental status of the uterus) was significantly decreased in the uterus of superovulated monkeys, and decreased expression of proliferation marker PCNA was found in uterine cells. Meanwhile, abnormal Golgi-derived secretory vesicles with an irregular shape were observed in the mammary glands of the superovulated monkeys, and decreased PCNA expression together with increased expression of caspase-3 (an apoptosis marker) was indicated in the mammary cells. The expression of tumor molecular markers of the uterus and mammary gland was not significantly different between the two groups.


Repeated COH affects the expression of the uterine development-related gene several years later, and uterine cells exhibited a low proliferation status. The ultrastructure of the mammary gland epithelial cells was abnormal, and the cells exhibited both low proliferation and high apoptosis status. Cancer risk for these organs was not observed. Given that primates are the closest relatives of humans, the results obtained from this study provide more intuitive information for optimization of clinical COH.


Safety assessment of ART Controlled ovarian hyperstimulation (COH) Uterus Mammary gland Rhesus monkey 



This work was supported by grants from the National Science Foundation of China (no. 31271604) and the Major State Basic Research Development Program of China (973 Program) (no. 2012CB944902).


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Peipei Yan
    • 1
  • Jingyi Xu
    • 1
  • Yan Zeng
    • 1
  • Guoying Dong
    • 1
  • Huarong Cao
    • 1
  • Meimei Zheng
    • 1
  • Hui Zhu
    • 1
  1. 1.State Key Laboratory of Reproductive Medicine, Department of Histology and EmbryologyNanjing Medical UniversityNanjingChina

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