Successful experimental infant baboon model for childhood cryptosporidiosis studies.

BACKGROUND: Cryptosporidiosis causes high morbidity and mortality in children under 2 years of age globally. The lack of an appropriate animal model that mimics the pathogenesis of disease in humans has hampered the development and testing of potential therapeutic options. This study aimed to develop and validate an infant baboon infection model of cryptosporidiosis. METHODS: Eighteen immunocompetent weaned infant baboons aged 12 to 16 months were used. The animals were n = 3 controls and three experimental groups of n = 5 animals each inoculated with Cryptosporidium parvum oocysts as follows: group 1: 2 × 104, group 2: 2 × 105, group 3: 2 × 106 followed by daily fecal sampling for oocyst evaluation. Blood sampling for immunological assay was done on the day of infection and weekly thereafter until the end of the experiment, followed by necropsy and histopathology. Statistical analysis was performed using R, SPSS, and GraphPad Prism software. Analysis of variance (ANOVA) and Bonferroni post hoc tests were used for comparison of the means, with p < 0.05 considered as a significant difference. Correlation coefficient and probit analysis were also performed. RESULTS: In all experimental animals but not controls, the onset of oocyst shedding occurred between days 2 and 4, with the highest oocyst shedding occurring between days 6 and 28. Histological analysis revealed parasite establishment only in infected animals. Levels of cytokines (TNF-α, IFN-γ, and IL-10) increased significantly in experimental groups compared to controls. CONCLUSION: For developing a reproducible infant baboon model, 2 × 104 oocysts were an effective minimum quantifiable experimental infection dose.

c-Jun NH2-terminal kinase inhibitor bentamapimod reduces induced endometriosis in baboons: an assessor-blind placebo-controlled randomized study.

OBJECTIVE: To test the hypothesis that the c-Jun NH2-terminal kinase (JNK) inhibitor (JNKI) bentamapimod (AS602801/PGL5001) can reduce induced endometriosis in baboons. DESIGN: Prospective randomized placebo-controlled study. SETTING: Nonhuman primate research center. ANIMAL(S): Twenty baboons each underwent four laparoscopies. Initial screening laparoscopy (L1) was followed after one rest cycle by an endometriosis-induction laparoscopy (L2). Fifty days after L2, the baboons were randomized just before staging laparoscopy (L3). Treatment lasted for 60 days, followed by a post-treatment staging laparoscopy (L4). INTERVENTION(S): Randomization before a 60-day treatment in four groups: daily placebo (n = 5), daily oral administration of 20 mg/kg JNKI (n = 5), concomitant daily oral administration of 20 mg/kg JNKI and 10 mg medroxyprogesterone acetate (MPA; n = 5), or subcutaneous administration of 3 mg cetrorelix every 3 days (n = 5). MAIN OUTCOME MEASURE(S): Type, surface area and volume of endometriotic lesions, and revised American Society for Reproductive Medicine score and stage were recorded during L3 and L4. Menstrual cycle length and serum hormonal concentration were recorded before and after treatment. RESULT(S): Compared with placebo, treatment with JNKI, JNKI + PMA, or cetrorelix resulted in lower total surface area and volume of endometriotic lesions. Remodeling of red active lesions into white lesions was observed more frequently in baboons treated with JNKI + MPA than in baboons treated with JNKI only. Menstrual cycle length and serum hormonal concentration were similar between placebo and JNKI groups. CONCLUSION(S): JNKI alone was as effective as JNKI + MPA or cetrorelix in reducing induced endometriosis in baboons, but without severe side effects or effect on cycle length or serum reproductive hormones.

Ovarian tissue cryopreservation by vitrification in olive baboons (papio anubis): a pilot study.

BACKGROUND: Ovarian tissue cryopreservation by vitrification is an attractive technique for fertility preservation in women. However, this technique has not been optimized. The aim of this study was to evaluate the baboon as a model for the preclinical study of ovarian tissue cryopreservation by vitrification and thawing. METHODS: Ovarian cortical tissues (1-mm cubes) were obtained surgically from adult female olive baboons (n = 9) maintained in captivity and vitrified using dimethyl sulphoxide and ethylene glycol protocol. The proportion of morphologically intact follicles (primordial, primary and secondary) in paired fresh and cryopreserved (vitrified-thawed) ovarian tissues was compared. RESULTS: Overall, 67.1% of follicles were morphologically normal after vitrification. When compared to fresh ovarian tissue, vitrified-thawed ovarian tissue contained a comparable number of intact primordial follicles (48.9 vs. 52.9%), and a lower number of both primary (14.8 vs. 29.5%; p < 0.05) and secondary (2.0 vs. 0.7%; p < 0.05) follicles. CONCLUSION: After vitrification and thawing, baboon ovarian tissue retains about 67% of morphologically normal follicles, which is comparable to results for human ovarian tissue, and suggests that the olive baboon is a promising animal model for preclinical assessment of ovarian vitrification, thawing and autotransplantation studies.

Short-term effects of high-dose khat on sperm parameters and reproductive hormonal levels in olive baboons (Papio anubis).

The biological effects of khat (Catha edulis) on reproduction and fertility are inadequately investigated and controversial, hence we determined the effects of oral administration of high-dose khat on sperm parameters and male hormonal levels in olive baboons. In this study, 6 male baboons received a high dose of khat (500 g/week) during 1 month. Electroejaculation for sperm studies (concentration, motility and chromatin integrity) and plasma collection for hormonal analysis (testosterone, prolactin and cortisol) were done weekly during 1 month before and 1 month during khat administration as well as 2 weeks after the last dose of khat administration. Administration of khat extract induced a significant reduction in sperm motility (p = 0.008), sperm count (p = 0.041), sperm chromatin integrity (p = 0.0003), testosterone levels (p = 0.035) and prolactin levels (p = 0.0115), but not in cortisol levels and sperm volume (p > 0.05). The results suggest that high-dose khat decreases sperm quality and testosterone and hence may contribute to male infertility.

Baboon spermatology: basic assessment and reproducibility in olive baboons (Papio anubis).

BACKGROUND: Development of a reproducible baboon in vitro fertilization (IVF) system require optimized and reproducible sperm parameters. The objective of this study was to document basic spermatology values and investigate the reproducibility of these variables in the same baboons 1 or 3 months later in a larger number of baboons. METHODS: In this prospective study, sperm quality (semen volume, pH, concentration, motility, morphology and size) was evaluated in 27 sperm samples obtained from 9 baboons electroejaculated three times with a time interval of 1 month (between first and second sample collection) and 3 months (between second and third round sample collection). RESULTS: Baseline sperm values for semen volume (0.5 ± 0.3 ml), pH (7.5 ± 0.3), concentration (54.2 ± 19.3 million/ml), motility (67.3 ± 18.5%) and morphology (89.2 ± 4.8%) were similar to sperm samples obtained after 1 or 3 months (P > 0.05). Head, midpiece and tail abnormalities were rarely observed (0-9%). Sperm dimensions were characterized by a tail length of 69.6 ± 13.9 µm, a head width of 2.41 ± 0.43 µm and a head length of 3.49 ± 0.6 µm. CONCLUSION: Sperm quality was not affected by repeated electroejaculation with time intervals of 1 or 3 months, suggesting that the same baboon can participate multiple times in reproductive research.

Randomized comparison of different ovarian stimulation regimens for assisted reproductive technology in baboons (Papio anubis).

OBJECTIVE: To compare different methods of ovarian stimulation (OS) for assisted reproductive technology in baboons. DESIGN: Prospective randomized study. SETTING: Institute of primate research. ANIMAL(S): Baboons (n = 10) were randomized into two groups (of five animals each) during three different cycles to compare six protocols of OS. INTERVENTION(S): Cycle 1: clomiphene citrate (CC) alone (group CC) versus CC and GnRH agonist (group CC-Ag); cycle 2: recombinant gonadotropins (GON) without GnRH agonist (group GON) versus GON and depot GnRH agonist (group GON-AgDepo-1); cycle 3: GON and depot GnRH agonist (group GON-AgDepo-2) versus GON and daily GnRH agonist in a classic long protocol (group GON-Ag). Oocyte aspiration was performed 34-36 hours after injecting 5,000 IU rhCG, followed by fertilization via intracytoplasmic sperm injection (ICSI). MAIN OUTCOME MEASURE(S): Number and quality of oocytes retrieved and their fertilization rate. RESULT(S): More metaphase II (MII) oocytes were retrieved using the GON-AgDepo-1 (n = 12; 64% MII), GON-AgDepo-2 (n = 9; 79% MII), GON-Ag (n = 16; 88% MII), and GON (n = 6; 59% MII) protocols compared with the CC (n = 9; 15% MII) and CC-Ag (n = 14; 20% MII) protocols. Fertilization by ICSI varied between 43% and 71%. CONCLUSION(S): In baboons, long and depot protocols yield similar numbers of MII oocytes; however, depot protocol may be preferable because only one injection of GnRH agonist is needed.

Peroxisome proliferator-activated receptor-(gamma) receptor ligand partially prevents the development of endometrial explants in baboons: a prospective, randomized, placebo-controlled study.

A prospective, randomized, placebo-controlled study was conducted in a baboon model to determine if a thiazolidinedione agonist of peroxisome proliferator-activated receptor-gamma, pioglitazone, can impede the development of endometriosis. Endometriosis was induced using laparoscopic, intrapelvic injection of eutopic menstrual endometrium, previously incubated with placebo or pioglitazone for 30 min, in 12 female baboons with a normal pelvis that had undergone at least one menstrual cycle since the time of captivity. At this point, the 12 baboons were randomized into two groups and treated from the day of induction. They received either PBS tablets (n = 6, placebo control, placebo tablets once a day by mouth) or pioglitazone (n = 6, test drug, 7.5 mg by mouth each day). A second and final laparoscopy was performed in the baboons to record the extent of endometriotic lesions between 24 and 42 d after induction (no difference in length of treatment between the two groups, P = 0.38). A videolaparoscopy was performed to document the number and surface area of endometriotic lesions. The surface area and volume of endometriotic lesions were significantly lower in pioglitazone treated baboons than the placebo group (surface area, 48.6 vs. 159.0 mm(2), respectively, P = 0.049; vol, 23.7 vs. 131.8 mm(3), respectively, P = 0.041). The surface area (3.5 vs. 17.8 mm(2), P = 0.017, pioglizatone vs. placebo) and overall number (1.5 vs. 9.5, P = 0.007, pioglizatone vs. placebo) of red lesions were lower in the pioglitazone group. A peroxisome proliferator-activated receptor-gamma ligand, pioglitazone, effectively reduced the initiation of endometriotic disease in the baboon endometriosis model. Using this animal model, we have shown that thiazolidinedione is a promising drug for preventive treatment of endometriosis.

Separate and combined effects of caffeine and dbcAMP on olive baboon (Papio anubis) sperm.

BACKGROUND: Improvement of baboon sperm capacitation is necessary for achieving high in vitro fertilization (IVF) rates in baboons. In this study, we evaluated separate and combined effects of caffeine and dbcAMP on baboon sperm capacitation. METHODS: Sixteen male baboons (n = 16) were electroejaculated. Each sperm sample was divided into two aliquots: one for chemical activation and the other untreated control. Group 1: dbcAMP (n = 6); Group 2: caffeine (n = 6) and Group 3: combination of caffeine and dbcAMP (n = 4). In each aliquot, sperm motility after 30 minutes of incubation was evaluated as well as zona pellucida (ZP) binding ability after overnight incubation with 4-5 ZP from unfertilized human oocytes. RESULTS: Sperm motility and ZP binding ability in all chemically activated groups increased significantly as compared to their respective controls (P < 0.05). CONCLUSION: Combined and separate effects of caffeine and dbcAMP increases baboon sperm motility and ZP binding ability and may improve baboon IVF.

Transplacental transfer of paclitaxel, docetaxel, carboplatin, and trastuzumab in a baboon model.

BACKGROUND: The paucity of data on fetal effects of prenatal exposure to chemotherapy prompted us to study the transplacental transport of commonly used anticancer agents in a pregnant baboon model. METHODS: Single or combination chemotherapy with paclitaxel, docetaxel, carboplatin, and trastuzumab was administered to 9 baboons at a mean (SD) gestational age of 117 (26) days (paclitaxel, 100 mg/m2 [n = 2]; docetaxel, 100 mg/m2 [n = 2]; paclitaxel, 175 mg/m2 with carboplatin, area under the curve of 6 at standard dosage [n = 2] and 50% dosage [n = 1]; docetaxel, 75 mg/m2 with carboplatin, area under the curve 6 [n = 1]; and docetaxel, 75 mg/m2 with trastuzumab, 8 mg/kg [n = 1]). Serial fetal and maternal blood samples, amniotic fluid, maternal urine, and fetal and maternal tissue samples were collected for the first 76 hours after drug infusion. Levels of carboplatin were determined by atomic absorption spectrometry, docetaxel and paclitaxel by high-performance liquid chromatography, and trastuzumab by enzyme-linked immunosorbent assay. RESULTS: Fetal plasma concentrations of carboplatin averaged 57.5% (14.2%) of maternal concentrations (n = 7). Fetal plasma concentrations were 1.5% (0.8%) of maternal concentrations (n = 7). Immediately after ending the infusion, paclitaxel was not detectable in fetal tissues, whereas, after 3 hours, fetal tissues contained 15% of maternal tissue concentrations.Docetaxel could not be detected in fetal blood samples (n = 9). In the first 3 hours after docetaxel infusion, fetal tissues contained 5.0% to 50.0% of maternal tissue concentrations, whereas equal fetal and maternal tissue concentrations were found after 26 and 76 hours.The transplacental passages of trastuzumab were 85.0% and 3.0%, 2 and 26 hours after trastuzumab infusion, respectively. After 26 hours, amniotic fluid contained 36.4% of the fetal plasma concentration. Fetal tissue concentrations varied between 5.0% and 14.0% of the maternal concentration. CONCLUSION: Variable plasma and/or tissue concentrations of taxanes, carboplatin, and trastuzumab were encountered in the fetal compartment. These data are important when cancer treatment is considered during pregnancy and underline the need for long-term follow-up of children after prenatal exposure to these cytotoxic agents.

Menstrual cycle synchronization, ovarian stimulation, and in vitro fertilization in olive baboons (Papio anubis): a prospective randomized study.

OBJECTIVE: To synchronize the baboon menstrual cycle and to compare different methods of ovarian stimulation for IVF in baboons. DESIGN: Prospective randomized study. SETTING: Institute of Primate Research, Nairobi, Kenya. ANIMAL(S): Ten female baboons were treated with an oral contraceptive (33 +/- 8 days) and randomized for ovarian stimulation in two cycles. INTERVENTION(S): In cycle 1 (C1), baboons were stimulated as follows: clomiphene citrate (CC) for 5 days followed by antagonist (group CC-1, n = 3); recombinant gonadotropins (rGn: rFSH and rLH) with antagonist (group antagon-1, n = 3); and long GnRH agonist protocol (group LP-1, n = 4). After 1- month rest, in cycle 2 (C2), the baboons were stimulated as follows: CC for 8 days without antagonist (group CC-2, n = 2); short GnRH agonist protocol (group SP-2, n = 4); long GnRH agonist protocol (group LP-2, n = 4). Oocyte aspiration was performed 34-36 hours after injecting 5000 IU recombinant hCG; the oocytes were then fertilized. MAIN OUTCOME MEASURE(S): Oocytes retrieved and fertilization rate. RESULT(S): Withdrawal bleeding occurred 4 +/- 1 days after the cessation of the contraceptive. Ovarian stimulation using the different protocols resulted in the following mean numbers of retrieved oocytes: LP-1, n = 19; LP-2, n = 19; CC-1, n = 4; CC-2, n = 4; antagon-1, n = 9; and SP-2, n = 14. Fertilization by intracytoplasmic sperm injection varied (23%-54%). CONCLUSION(S): The baboon menstrual cycle can be synchronized using an oral contraceptive. A long GnRH agonist protocol for ovarian stimulation may be suitable for ovarian stimulation in baboons.

Feasibility of ultrasound-guided percutaneous samplings in the pregnant baboon: a model for studies on transplacental transport.

OBJECTIVE: A study was conducted to test the feasibility of cordocenteses and amniocenteses at different gestational ages in pregnant baboons. STUDY DESIGN: Experiments were performed in 10 pregnant baboons at a median gestational age of 131 (range 92-169) days. At different time intervals, percutaneous samplings of amniotic fluid and fetal blood were performed under ultrasound guidance. Simultaneously, maternal blood samples were drawn. RESULTS: With a median fetal weight of 431 g (range 111-690 g), 29 of 30 cordocenteses (96.6%) and all 30 amniocenteses and maternal samplings (100%) were successful in obtaining the required quantities for analysis. One cordocentesis was abandoned because of insufficient visualization of the umbilical cord due to a placental haemorrhage. CONCLUSION: Percutaneous amniocentesis and cordocentesis can be performed with a high success rate in the pregnant baboon model. In combination with a 100% success rate in obtaining simultaneous maternal blood samples, this method is able to provide data on transplacental transport.

Effects of anti-TNF-mAb treatment on pregnancy in baboons with induced endometriosis.

OBJECTIVE: Hormonal suppressive therapy is not effective for endometriosis-associated subfertility and can even prevent conception. Medical inhibition of TNFalpha, which has been shown to improve conception, is effective in the prevention and treatment of endometriosis in baboons. DESIGN: Prospective, placebo-controlled fertility trial. SETTING: Animal research and laboratory facility. ANIMAL(S): Sixteen adult female baboons with induced endometriosis. INTERVENTION(S): All animals received a single IV dose of the anti-TNFalpha monoclonal antibody c5N (n = 9) or placebo (n = 7) at four different time points. The animals were then exposed to timed mating up to nine completed cycles or until pregnancy was achieved. MAIN OUTCOME MEASURE(S): Pregnancy rate (PR), cycle fecundity rate (CFR), time to pregnancy (TTP), and cumulative pregnancy rate (CPR). RESULT(S): Inhibition of TNFalpha did not result in a significant improvement in PR (100% c5N vs. 86% placebo), CFR (18% c5N vs. 30% placebo), median TTP (5 cycles c5N vs. 2 cycles placebo), or CPR (100% c5N vs. 80% placebo). The duration of the menstrual cycle was unchanged in both groups before and after the study. Two nonpregnant baboons in the c5N-group died during the study. CONCLUSION(S): Medical inhibition of TNFalpha allowed for normal conception but did not improve fecundity in baboons with induced endometriosis when compared with placebo. Larger studies with clinically available TNFalpha blockers in baboons with moderate to severe endometriosis are needed to further test the potential of these agents in the prevention or treatment of endometriosis-associated subfertility.

The baboon as a research model for the study of endometrial biology, uterine receptivity and embryo implantation.

The process of embryo implantation includes attachment of the embryo to the endometrium and penetration through the epithelial layer, decidualization of the basement membrane, invasion of the uterine stroma and access to blood supply. This implantation process is very different in humans when compared to pigs, cattle or rodents. The process of invasion in humans where the embryo gets embedded in decidual tissue and in spiral arteries is more aggressive, but otherwise similar to the process of implantation and invasion in non-human primates such as rhesus monkeys and baboons. For ethical reasons, it is unacceptable to study directly the process of embryo implantation in women, and to this day, this remains one of the 'black boxes' of reproductive science. Indeed for many clinicians practicing reproductive medicine, in fertility centers, the most difficult question and of concern asked by patients is: 'Why do my healthy appearing embryos not implant: is there a problem with my endometrium or uterus?' The olive baboon (Papio anubis anubis) is an excellent animal model for reproductive research. In contrast with smaller non-human primates like rhesus monkeys or cynomolgus monkeys, it is possible in baboons to use transcervical uterine probes (curettes, catheters and hysteroscopic equipment) to perform endometrial biopsy, embryo flushing or transfer and hysteroscopy in a non-invasive way. This can be done easily in multiparous baboons during menstruation, but may be more difficult at the end of the follicular phase (maximal perineal swelling impedes vaginal/cervical access) or during the luteal phase (narrow cervix), in nulliparous baboons and in animals with abnormal internal genitals. In this paper we present an overview regarding the potential of the baboon model to study in vivo uterine receptivity and embryo implantation using invasive and non-invasive approaches.

PPAR-gamma receptor ligand induces regression of endometrial explants in baboons: a prospective, randomized, placebo- and drug-controlled study.

OBJECTIVE: To determine the effects of a thiazolidinedione (TZD) agonist of peroxisome proliferator-activated receptor (PPAR)-gamma, rosiglitazone, in a baboon model of established endometriosis. DESIGN: Prospective, randomized, placebo-controlled study. SETTING: Experimental surgery laboratory at the Institute of Primate Research in Nairobi, Kenya. ANIMAL(S): Endometriosis was induced using intrapelvic injection of eutopic menstrual endometrium in 12 female baboons with a normal pelvis that had undergone at least one menstrual cycle since the time of captivity. INTERVENTION(S): Induction of endometriosis by laparoscopy was performed in 12 baboons with a normal pelvis. Endometrial tissue was extracted from each baboon by curettage, and a standard amount of endometrium was then seeded onto several peritoneal sites. About 34-68 days after the induction of laparoscopy, a pretreatment laparoscopy (baseline disease assessment) was performed in the baboons to record the extent of endometriotic lesions. The 12 baboons were randomized into three groups and treated from the day after the staging laparoscopy for a total duration of 30 days. They received phosphate-buffered saline tablets (n = 4, placebo control; placebo tablets once a day by mouth for 30 days), GnRH-antagonists (n = 4, active control; ganirelix acetate 125 microg/day for 30 days), or rosiglitazone (n = 4, test drug, 2 mg by mouth each day for 30 days). A third and final laparoscopy on day 30 after the start of treatment was performed to record the extent of endometriosis. The type of lesion (typical, red, white, or suspicious) was recorded. Biopsies were obtained to confirm the histological presence of endometriosis. MAIN OUTCOME MEASURE(S): A videolaparoscopy was performed 30 days after treatment to document the number and surface area of endometriotic lesions as well as to calculate the revised American Society for Reproductive Medicine score and stage. RESULT(S): The surface area of endometriotic lesions was statistically significantly lower in rosiglitazone-treated baboons when compared with the placebo group. Baboons treated with rosiglitazone or ganirelix had a greater negative relative change in surface area of peritoneal endometriotic lesions than controls. The overall weighted appearance of the lesion types suggests that rosiglitazone may deter the development of newer endometriotic lesions. CONCLUSION(S): A PPAR-gamma ligand, rosiglitazone, effectively diminishes the burden of endometriosis disease in a baboon endometriosis model. This animal model holds promise that a TZD drug may be helpful in women with endometriosis.

Endometriosis in African women.

Endometriosis is a gynecological disorder characterized by the growth of endometrial tissue outside the uterine cavity. Although the prevalence of endometriosis is well documented in women living in developed countries, studies on the prevalence of this disease among African women are still wanting. The current view is that endometriosis rarely affects women of African descent. However, in African-American women in the USA, endometriosis is one of the common indications for major gynecological surgery and hysterectomy and is associated with a long hospitalization and high hospital charges. Endometriosis may be more commonly found in infertile Caucasian or African-American women than in African-Indigenous women, but it is likely that the true prevalence of endometriosis in African-Indigenous women is under reported owing to inadequate facilities and demands of specialized skills for adequate assessment of the pelvis and recognition of the various types and appearances of the disease. Understanding the prevalence of endometriosis among African women will be instrumental in proper management of this disease in the African continent.

Recombinant human TNFRSF1A (r-hTBP1) inhibits the development of endometriosis in baboons: a prospective, randomized, placebo- and drug-controlled study.

Endometriosis is associated with chronic inflammation, including an increased macrophage activity with increased secretion of cytokines, such as tumor necrosis factor (TNF) or TNF superfamily member 2, previously known as TNFalpha. In the present study, we tested the hypothesis that recombinant human TNFRSF1A (r-hTBP1) can inhibit the development of endometriotic lesions in the baboon, an established model for the study of endometriosis. Endometriosis was induced using intrapelvic injection of menstrual endometrium in 20 baboons with a normal pelvis. In the first part of the study, 14 baboons were randomly assigned to subcutaneous treatment with r-hTBP1, placebo, or GnRH antagonist (positive control). In the second part of the study, menstrual endometrium from 6 baboons was randomly incubated with either PBS or r-hTBP1 before intrapelvic seeding. Video laparoscopy was performed 25 days later to document the number, surface area, and estimated volume of endometriotic lesions and adhesions; to calculate the revised American Fertility Society (rAFS) score and stage; and to confirm the histological presence of endometriosis. In the first part, baboons treated with r-hTBP1 or with Antide (Bachem) had a lower endometriosis rAFS score, a lower surface area and estimated volume of peritoneal endometriotic lesions, and a lower histological confirmation rate compared with controls. Because of less adnexal and cul-de-sac adhesions, the number of baboons with endometriosis of stage II, III, or IV was lower among baboons treated with r-hTBP1 or Antide than among controls. In the second part, the surface area of endometriotic lesions was lower, and less severe endometriosis was observed in r-hTBP1-treated baboons. No hypoestrogenic effects were observed in baboons treated with r-hTBP1. In conclusion, r-hTBP1 can effectively inhibit the development of endometriosis without hypoestrogenic effects in baboons.