Charanjit S. Bambra

Intrapelvic injection of menstrual endometrium causes endometriosis in baboons (Papio cynocephalus and Papio anubis)

OBJECTIVE The Sampson hypothesis of retrograde menstruation as a cause of endometriosis was tested by determining the effect of intrapelvic injection of menstrual versus luteal endometrium on the incidence, peritoneal involvement, and stage of endometriosis. STUDY DESIGN Seventeen baboons were injected retroperitoneally with luteal (n = 6) or menstrual (n = 7) endometrium and intraperitoneally with menstrual endometrium (n = 4). Laparoscopies were performed after 2 months in all animals and after 5 and 12 months in six and five primates injected with luteal and menstrual endometrium, respectively. RESULTS The peritoneal endometriosis surface area, number of implants, and incidence of typical and red subtle lesions were significantly higher after retroperitoneal injection of menstrual than of luteal endometrium. By use of menstrual endometrium intraperitoneal seeding was more successful in causing endometriosis than was retroperitoneal injection. No significant changes in number or surface area of endometriotic lesions induced with retroperitoneal injection of luteal endometrium after 5 months were observed in the six baboons. At repeat laparoscopy 12 months after intrapelvic injection of menstrual endometrium progression was recorded in three of four regularly cycling animals, whereas regression was evident in one baboon that had become amenorrheic after induction. CONCLUSION Intrapelvic injection of menstrual endometrium can cause peritoneal endometriosis and offers experimental evidence supporting the Sampson hypothesis.

Serial laparoscopies over 30 months show that endometriosis in captive baboons (Papio anubis, Papio cynocephalus) is a progressive disease

OBJECTIVE To test the hypothesis that spontaneous endometriosis is a progressive disease in baboons. DESIGN AND SETTING Prospective cohort study, Institute of Primate Research, Nairobi, Kenya. PARTICIPANTS Twelve baboons with histologically proven spontaneous endometriosis. INTERVENTIONS Fifty-four serial laparoscopies (4.2 +/- 1.9 per animal, range 1 to 7) were performed after 1 to 3 months (n = 2), 4 to 6 months (n = 1), 7 to 9 months (n = 6), 10 to 12 months (n = 17), 13 to 15 months (n = 7), 16 to 18 months (n = 1), 19 to 21 months (n = 8), 22 to 24 months (n = 8), 25 to 27 months (n = 2), and 30 to 32 months (n = 2). MAIN OUTCOME MEASURE During each laparoscopy the pelvis was examined for the presence of endometriosis. The number, size, and type of endometriotic implants were noted on a pelvic map and both endometriosis score and stage were calculated. Remodeling was defined as a change in laparoscopic appearance (typical, subtle, suspicious) of an individual endometriotic lesion. Data were analyzed by a signed rank test. RESULTS Endometriosis was progressive as shown by the significant increase in the number and surface of lesions and in endometriosis scores after 24 months. The total number of endometriotic lesions after 24 months consisted of 69% new (and mostly subtle) implants, 10% remodeled lesions, and 21% unchanged implants. CONCLUSIONS This study demonstrated that endometriosis in captive baboons undergoing repeated laparoscopies is a dynamic and moderately progressive disease with periods of development and regression and active remodeling between different types of lesions.

The prevalence of spontaneous endometriosis in the baboon (Papio anubis, Papio cynocephalus) increases with the duration of captivity

Background. It is not known whether stress affects the prevalence of endometriosis in women. Baboons with spontaneous endometriosis may be interesting models to study the human disease. For baboons, living in captivity is a period of chronic stress without continuous exposure to pregnancy. This study was done to compare the prevalence of endometriosis between baboons recently captured in the wild and those living in captivity for several years. Methods. A diagnostic laparoscopy was performed for screening endometriosis and obtaining biopsies in 104 female baboons including animals that had been captured in the wild less than 1 year ago (n=52. Group I), primates that had been living in captivity for one to two years (n=30. Group II) and animals that had been captured for more than two years (n=22, Group III).

Evolution of spontaneous endometriosis in the baboon (Papio anubis, Papio cynocephalus) over a 12-month period*

To document the spontaneous evolution of endometriosis, a repeat laparoscopy was performed in 11 baboons after 10 and/or 12 months. The mean number of endometriotic lesions had increased significantly after 10 months (P less than 0.02) because of a high proportion of new lesions (82%). These implants were mainly subtle (67%) and localized on the uterine peritoneum (58%). Progression of endometriosis did not go beyond revised AFS stage I. Additionally, repeat laparoscopy in 10 baboons with an initially normal pelvis showed an endometriosis incidence of 70% after 10 to 12 months. Remodeling of the lesions was apparent in both groups after 12 months. These results suggest that endometriosis is moderately progressive in the baboon. It is possible that multiple laparoscopies could favor the development of endometriosis.

Evaluation of trophoblast invasion in placental bed biopsies of the baboon, with immunohistochemical localisation of cytokeratin, fibronectin, and laminin

Abstract: Biopsies of placentas (n = 21), placental bed (n = 17) and decidua (n = 26) of various gestation periods (30 to 140 days) were used to study trophoblast invasion in the baboon. Application of immunohistochemical staining for cytokeratin allowed proper identification of trophoblast. Earlier reports showing restricted trophoblast invasion in this species were confirmed by the finding that endovascular trophoblast was present in only one third of biopsies containing spiral arteries. Moreover, immunostaining for cytokeratin revealed that in several arteries only a few isolated trophoblastic cells were present, while the vessel had not undergone the normal physiological change. Trophoblast invasion could only be detected within decidual, but not in myometrial, segments of spiral arteries. Interstitial trophoblast invasion was very limited and multinuclear giant cells were absent. Immunohistochemical staining suggested a contribution of laminin to the fibrinoid deposition within the physiologically changed spiral arteries, while fibronectin was present intracellularly in the invaded trophoblast. Because of differences in the trophoblast invasion pattern, the baboon cannot be regarded as a satisfactory experimental model to explore results of inadequate endovascular trophoblast invasion which, in the human, leads to pregnancy complications such a preeclampsia.

The cycle pregnancy rate is normal in baboons with stage I endometriosis but decreased in primates with stage II and stage III-IV disease.

OBJECTIVES To test the hypothesis that fertility is reduced in baboons with endometriosis. DESIGN Prospective controlled follow-up study. SETTING Institute of Primate Research, Nairobi Kenya. SUBJECTS Seventy-one baboons, including 34 controls (normal pelvis) and 37 animals with histologically proven endometriosis (16 spontaneous and 21 induced). Baboons with endometriosis had minimal (n = 9), mild (n = 14), moderate (n = 7), or severe (n = 7) disease. INTERVENTIONS Seventy-one baboons were mated during 286 cycles. MAIN OUTCOME MEASURES Cycle fecundity rate, cycle pregnancy rate, cycle abortion rate. RESULTS Cycle pregnancy rate (excluding spontaneous abortions) was 15% (44/286) and was comparable between controls (19%, 20/104) and baboons with endometriosis (13%, 24/182). The cycle pregnancy rates were 24%, 10%, 7.5%, and 12.5% in animals with minimal, mild, moderate, and severe endometriosis, respectively. The cycle pregnancy rate was significantly lower in baboons with stage III-IV endometriosis (9%, 6/64) and with stage II disease (10%, 7/73) than in animals with stage I endometriosis (24%, 11/45) or in controls with a normal pelvis (19%). CONCLUSION The normal cycle pregnancy rate in baboons with stage I endometriosis and the decreased cycle pregnancy rate in baboons with stage II and stage III-IV disease suggest that fertility decreases with the stage of endometriosis in baboons.

Development of spontaneous endometriosis in baboons

Objective To determine the incidence of spontaneous endometriosis over a 32-month period in baboons with initially normal pelves. Methods In this observational longitudinal study, which was performed at the Institute of Primate Research, Nairobi (Kenya), 24 baboons with laparoscopically confirmed normal pelves underwent 67 serial laparoscopies (mean 2.8 ± 1.9, median 3, range 1–6) after 1–3 months (n = 8), 4–6 months (n = 11), 7–9 months (n = 9), 10–12 months (n = 17), 13–15 months (n = 6), 16–18 months (n = 4), 19–21 months (n = 3), 22–24 months (n = 4), 25–27 months (n = 1), and 30–32 months (n = 4). During each laparoscopy, the pelvis was examined for the presence of endometriosis. The number, size, and type of endometriotic implants were noted on a pelvic map, and the endometriosis score and stage were tabulated according to the revised classification of the American Fertility Society. Taking into account the variable length of follow-up, we used life-table analysis to calculate the cumulative incidence of endometriosis. Results The cumulative incidence of minimal endometriosis (proven by histology) was 64% up to 32 months of follow-up. The eight baboons that developed proven endometriosis were followed over longer periods of time and had undergone more laparoscopies than the animals that did not develop the condition. Conclusion There is a high incidence of minimal endometriosis in baboons, which increases with the time of follow-up and the number of repeat laparoscopies.

The effects of immunosuppression on development and progression of endometriosis in baboons (Papio anubis)

OBJECTIVE To test the hypothesis that immunosuppression increases the development and progression of endometriosis in baboons. DESIGN Experimental controlled study. SETTING Institute of Primate Research, Nairobi, Kenya. PARTICIPANTS Thirty-two baboons (8 with normal pelvis, 10 with spontaneous endometriosis, and 14 with endometriosis induced by intraperitoneal seeding of menstrual endometrium). INTERVENTION Daily injection of 0.8 mg/kg IM methylprednisolone and 2 mg/kg azathioprine for 3 months in 16 baboons (4 with normal pelvis, 5 with spontaneous endometriosis, and 7 with induced endometriosis). No treatment was given to the remaining 16 primates. MAIN OUTCOME MEASURES The change in number and surface area (mm2) of endometriotic lesions was evaluated by laparoscopy in all baboons after 3 months, in 8 animals with induced endometriosis and in 9 primates with spontaneous disease after 7 and 12 months, respectively. RESULTS Immunosuppressed baboons with spontaneous endometriosis had a significantly higher number and larger surface area of endometriotic lesions than nontreated animals. However, immunosuppressed and nontreated primates with induced endometriosis were comparable with respect to both number and surface area of implants. A transient decrease in typical lesions was noted during immunosuppression. Immunosuppression did not cause the development of endometriosis in baboons with previously documented normal pelvis. CONCLUSION Immunosuppression may increase the progression of endometriosis in baboons with spontaneous disease.

Pelvic inflammation induced by diagnostic laparoscopy in baboons

OBJECTIVE To test the hypothesis that diagnostic laparoscopy can cause pelviperitoneal inflammation. DESIGN Retrospective analysis of data collected during a prospective controlled study in baboons. SETTING An academic research environment. ANIMAL(S) Samples were collected during laparoscopies in female baboons at the Institute of Primate Research, Kenya. INTERVENTION(S) In the first part of the study, 44 laparoscopies were performed in 16 baboons (5 with a normal pelvis, 11 with endometriosis) during the luteal phase, with a time interval of 1 month. In the second part of the study, 53 laparoscopies were performed in 15 baboons (6 with a normal pelvis, 9 with endometriosis) during the late follicular and luteal phases of one cycle, with a median time of 3-4 days between each laparoscopy. MAIN OUTCOME MEASURE(S) Peritoneal fluid (PF) was measured and analyzed for white blood cell (WBC) concentrations and, in the second part of the study, for the distribution of lymphocyte subsets (CD3, CD4, CD8, and CD20) and for the presence of cytokines transforming growth factor-beta1, interleukin (IL)-6, and IL-10. RESULT(S) In the first part of the study, PF volumes and WBC concentrations were comparable at the baseline and follow-up laparoscopies. In the second part of the study, PF obtained at the second laparoscopy showed a 10-fold increase in volume, a 3-fold increase in WBC concentration, a 10-fold increase in IL-6 concentration, and a 2-fold increase in transforming growth factor-beta1 concentration when compared with PF obtained at the first laparoscopy. The PF subset of granulocytes and CD3-positive cells was higher and the PF subset of macrophages was lower at follow-up laparoscopies than at the baseline laparoscopy. CONCLUSION(S) Diagnostic laparoscopy can cause peritoneal inflammation in baboons.

THE EFFECT OF PREGNANCY ON ENDOMETRIOSIS IN BABOONS (PAPIO ANUBIS, PAPIO CYNOCEPHALUS)

Abstract.Background: This study was performed to test the hypothesis that endometriosis undergoes regression during pregnancy. Methods: This study was performed on 11 baboons with histologically proven endometriosis, housed at the Institute of Primate Research, Nairobi, Kenya. In each individual baboon paired laparoscopies were performed prior to and during pregnancy (6 during first and 5 during second trimester of gestation) with an interval of 5±3 months. During each laparoscopy the number, size and type of endometriosis implants were noted in detail on a pelvic map; the endometriosis score and stage were calculated according to the revised American Fertility Society (AFS) classification. In each baboon the observations prior to and during pregnancy were compared and analysed by Wilcoxon signed rank test (two-tailed). Results: No significant change was observed in the AFS score or stage of endometriosis, or in the number, size and type of endometriotic lesions in baboons during gestation when compared to the nonpregnant state. Conclusion: In baboons pregnancy had no significant effect on endometriosis during the first or second trimester of gestation.