New theca-cell marker insulin-like factor 3 is associated with premature ovarian insufficiency

Circulating levels of insulin-like factor 3 (INSL3) decline as ovarian insufficiency progresses, which may serve as a promising theca-cell specific marker for premature ovarian insufficiency.

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VOLUME 115, ISSUE 2, P455-462


Chendi Zhu, M.D., Wei Luo, M.D., Zhuqing Li, M.D., Xiruo Zhang, M.D., Jingmei Hu, M.D., Ph.D., Shidou Zhao, M.D., Ph.D., Xue Jiao, M.D., Ph.D., Yingying Qin, M.D., Ph.D.



To characterize circulating insulin-like factor 3 (INSL3) in different stages of ovarian insufficiency and its role in the evaluation of premature ovarian insufficiency (POI).


Retrospective cohort study.


University-based center for reproductive medicine.


A total of 145 women, including 48 patients with POI (25 IU/L < follicle-stimulating hormone [FSH] ≤40 IU/L), 49 with biochemical POI (bPOI) (10 IU/L < FSH ≤25 IU/L) and 48 age-matched control women with normal ovarian reserve (FSH <10 IU/L), retrospectively included from the reproductive hospital affiliated with Shandong University between 2017 and 2019.


Levels of INSL3 in the serum and follicular fluid assayed with a commercial radioimmunoassay.

Main Outcome Measure(s)

Level of INSL3 in serum and follicular fluid among control women and patients with bPOI and POI, its association with different ovarian reserve markers, and its predictive value for bPOI and POI.


The serum INSL3 level continuously declined with the progress of ovarian insufficiency. It showed strong negative association with FSH (−0.655) and luteinizing hormone (−0.433), but positively correlated with antimüllerian hormone (0.617), inhibin B (0.400), antral follicle count (0.630), and testosterone (0.180). Additionally, the circulating INSL3 served as a good predictor for bPOI and POI. No statistically significant difference of INSL3 levels in follicular fluid was observed between bPOI patients and control women.


For the first time our study has revealed an INSL3 deficiency in women with POI, indicating that circulating INSL3 could serve as a promising theca-cell specific marker for POI. Future research on the role of INSL3 in modulating follicular development, steroidogenesis, and POI pathogenesis is warranted.

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.