A Mouse Model for Dietary Xenosialitis ANTIBODIES TO XENOGLYCAN CAN REDUCE FERTILITY

Fang Ma; Liwen Deng; Patrick Secrest; Linda Shi; June Zhao; Pascal Gagneux

doi:10.1074/jbc.M116.739169

A Mouse Model for Dietary Xenosialitis

ANTIBODIES TO XENOGLYCAN CAN REDUCE FERTILITY*

From the ^‡Sichuan University – The Chinese University of Hong Kong Joint Laboratory for Reproductive Medicine, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, and
^§Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China and
the ^¶Glycobiology Research and Training Center and Department of Pathology,
^‖Department of Bioengineering, and
^**Transgenic Mouse Core, University of California – San Diego, La Jolla, California 92093

↵1 To whom correspondence should be addressed: 9500 Gilman Dr., University of California, San Diego, La Jolla, CA 92093-0687. Tel.: 858-822-4030; Fax: 858-534-5611; E-mail: pgagneux{at}ucsd.edu.

Abstract

Humans can incorporate the xenoglycan N-glycolylneuraminic acid (Neu5Gc) from the diet into reproductive tissues and secretions. Most humans also have circulating antibodies specific for this dietary xenoglycan. The potential for inflammation induced by incorporated Neu5Gc and circulating anti-Neu5Gc antibodies, termed xenosialitis, has been discussed as a factor influencing several human diseases. Potential effects of xenosialitis on human fertility remain unknown. Here, we investigate possible adverse effects of the presence of Neu5Gc on sperm or endometrium combined with anti-Neu5Gc antibodies in semen or uterine secretions in a mouse model. We use Cmah^−/− mice, humanized for Neu5Gc deficiency. We find that the viability, migration, and capacitation of sperm with incorporated Neu5Gc are negatively affected when these are exposed to anti-Neu5Gc antibodies. In addition, we find that after copulation, activated uterine neutrophils and macrophages show increased phagocytosis of sperm in the presence of anti-Neu5Gc antibodies via the complement receptor 3 (C3R) and Fcγ I/II/III (Fc receptor). Furthermore, Neu5Gc in endometrial cells combined with the presence of anti-Neu5Gc antibodies alters the receptivity and decidualization of endometrial explants. These studies provide mechanistic insights on how Neu5Gc on sperm and/or endometrium combined with anti-Neu5Gc antibodies in semen and uterine fluid might contribute to unexplained human infertility.

Footnotes

↵* This work was supported by National Institutes of Health Grant GM1R01GM095882. The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.