Inhibition of ghrelin signaling improves the reproductive phenotype of male ob/ob mouse

Ghrelin signaling is involved in the reproductive phenotype of ob/ob mouse.

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Chu-Chao Zhu, B.Sc., Hua Zhang, M.D., Jin-Shan Zhang, M.D., Zhen Li, M.D., Jie Zhao, B.Sc., Wei Li, M.D., PhD., Yuan-Qiang Zhang, M.D.

Volume 99, Issue 3, Pages 918-926, 1 March 2013



To investigate whether ghrelin signaling is involved in the pathogenesis of male infertility induced by leptin deficiency.


Experimental study.


University academic medical center.


Ten-week-old C57BL/6J mice and ob/ob mice.


Western blotting, (quantitative) reverse transcription–polymerase chain reaction, immunohistochemistry and in situ end labeling of fragmented DNA.

Main Outcome Measure(s):

Expression levels of ghrelin and its functional receptor GHS-R1α were examined by western blotting and immunohistochemistry. Ob/ob mice were injected intraperitoneally with specific GHS-R1α antagonist and thereafter germ cell apoptosis and steroidogenic capability were assessed by TUNEL assay, (q)PCR and radioimmunoassay.


Expression of growth hormone (GH) secretagogue receptor 1a (GHS-R1α) and its endogenous ligand ghrelin was both up-regulated in ob/ob testis. Inhibition of ghrelin pathway restored androgen synthesis, reduced germ cell apoptosis and thereby resulted in improved sperm production in ob/ob mice.


Ghrelin, as an antagonistic partner of leptin in the endocrinic/paracrine circuit, may be involved in the pathogenesis of male infertility induced by leptin deficiency.

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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. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.