Effects of gremlin-2 on the transition of primordial follicles during early folliculogenesis in the human ovary

Yuki Ikeda, Akiko Hasegawa, Hiroshi Tsubamoto, Yu Wakimoto, Kanako Kumamoto, Hiroaki Shibahara

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Objective: To investigate the localization and function of gremlin-2 during human ovarian folliculogenesis. Study design: Ovarian tissue from a gynecologic cancer patient was cultured in the presence or absence of gremlin-2 and then analyzed histologically. Growing follicles were counted by the microscopic observations of ovarian histological sections. Immunocytochemical staining was carried out to detect the expression of bone morphogenetic protein (BMP) 4 and phosphorylated Smad 1/5/8 (p-Smad 1/5/8). Results: Gremlin-2 was detected in human primordial, primary, and early growing follicles before culture. By day 4 of culture, the follicle growth rate in the presence of gremlin-2 (13.7%; 24/175) was significantly lower than that of the control (54.8%; 92/175; p < 0.01). BMP4 expression was similar in the presence and absence of gremlin-2, whereas the p-Smad 1/5/8 signal was noticeably stronger in the absence of gremlin-2 in primordial and early-stage growing follicles. Conclusions: Gremlin-2 maintains the follicle store as primordial follicles by suppressing Smad 1/5/8 signaling in the human ovary. The data presented here provide potential insight into reproductive medicine for cases of intractable infertility, such as premature ovarian insufficiency and cancer survivors.

Original languageEnglish
Pages (from-to)72-77
Number of pages6
JournalEuropean Journal of Obstetrics and Gynecology and Reproductive Biology
Publication statusPublished - 01-08-2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Obstetrics and Gynaecology


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