Tohoku J. Exp. Med., 2020 June, 251(4)

The Natural History of Spontaneously Occurred Endometriosis in Cynomolgus Monkeys by Monthly Follow-Up Laparoscopy for Two Years

KAORI HAYASHI,¹ MISAKO NAKAYAMA,² CHIZURU IWATANI,³ HIDEAKI TSUCHIYA,³ SHINICHIRO NAKAMURA,³ KOSUKE NONOGUCHI,⁴ YASUSHI ITOH,² SHUNICHIRO TSUJI,¹ HIROHITO ISHIGAKI,² TAKAHIDE MORI,⁵ TAKASHI MURAKAMI¹ and KAZUMASA OGASAWARA²

¹Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu, Shiga, Japan
²Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan
³Research Center for Animal Life Science, Shiga University of Medical Science, Otsu, Shiga, Japan
⁴Infertility Center, Daigo Watanabe Clinic, Kyoto, Kyoto, Japan
⁵Academia for Reproductive and Regenerative Medicine, Doujin Hospital, Kyoto, Kyoto, Japan

Endometriosis, a disease in which endometrial tissue proliferates outside the uterus, is a progressive disease that affects women in reproductive age. It causes abdominal pain and infertility that severely affects the quality of life in young women. The mechanism of the onset and development of endometriosis has not been fully elucidated because of the complex mechanism involved in the disease. Nonhuman primates have been used to study the pathogenesis of spontaneous endometriosis because of their gynecological and anatomical similarities to humans. To reveal the natural history of endometriosis in cynomolgus monkeys, we selected 11 female cynomolgus monkeys with spontaneous endometriosis and performed monthly laparoscopies, mapping endometriotic lesions and adhesions up to two years. At the initial laparoscopy, endometriotic lesions were exclusively found in the vesicouterine pouch in 45.4% (5/11) of the monkeys and spread to the Douglas' pouch over time. Appearance of small de novo lesions and disappearance of some of the small lesions were observed in 100% (11/11) and 18.2% (2/11) of the monkeys, respectively. Endometriosis developed in all monkeys, and the speed of progression varied greatly among individuals that could be attributed to the degree or frequency of retrograde menstruation and genetic factors; these findings support the similarities between humans and monkeys, thus verifying the value of this nonhuman primate model. Finding reliable quantification markers and unravelling the underlying factors in correlation with the spatiotemporal development of the disease using a nonhuman primate model would be useful for the better management of endometriosis in humans.

Keywords —— cynomolgus monkey; endometriosis; laparoscopy; natural history of endometriosis; spontaneous endometriosis

© 2020 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2020, 251, 241-253

Correspondence: Misako Nakayama, Department of Pathology, Shiga University of Medical Science, Seta-tsukinowa cho, Otsu, Shiga 520-2192, Japan.

e-mail: miema@belle.shiga-med.ac.jp