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Placenta Accreta in an Oragnutan (Pongo abelii) and a Chimpanzee (Pan troglodytes)
J. Comp. Path. 2020, Vol. 174, 13e17
Available online at www.sciencedirect.com
ScienceDirect www.elsevier.com/locate/jcpa
DISEASE IN WILDLIFE OR EXOTIC SPECIES
Placenta Accreta in an Oragnutan (Pongo abelii) and a Chimpanzee (Pan troglodytes) L. Johnson*, T. Y. Khong†, A. Rallis‡, L. Woolfordx, C. Brandǁ and I. Smith{ * Zoos SA, Monarto Zoo, Monarto, † SA Pathology, Women’s and Children’s Hospital, North Adelaide, ‡ Women’s Health Specialists, North Adelaide, x School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, ǁ Tea Tree Gully Veterinary Hospital, Tea Tree Gully and { Zoos SA, Adelaide Zoo, Adelaide
Summary Placenta accreta is defined as abnormal adherence of the placenta to the uterine wall. Placenta accreta is recognized as a common problem in human medicine, but has apparently not been reported previously in great apes, despite similarity in their reproductive biology. A 36-year-old multiparous female Sumatran orangutan (Pongo abelii) and a 20-year-old nulliparous female chimpanzee (Pan troglodytes), with gross uterine and histological uterine vascular changes that are characteristic of placenta accreta, are presented. Ó 2019 Elsevier Ltd. All rights reserved. Keywords: chimpanzee; orangutan; pathology; placenta accreta
Placenta accreta is defined as abnormal adherence of the placenta to the uterine wall (Khong, 2008). The prevalence in women was estimated to be 1 in 30,000 deliveries, prior to the recent increase in the use of caesarean section for deliveries, and in population studies published between 1982 and 2018 ranged between around 1 in 100 and 1 in 10,000 (Jauniaux et al., 2019). To the best of our knowledge, there are no reported cases of placenta accreta in orangutans (Pongo abelii), chimpanzees (Pan troglodytes) or other great apes. However, the reproductive biology of these species is strikingly similar to that of man (Carter and Pijnenborg, 2011; Pijnenborg et al., 2011; Crosley et al., 2013). Orangutans, chimpanzees and other great apes are likely to be susceptible to a similar range of reproductive complications, as recently reported for preeclampsia (Crosley et al., 2013). A 36-year-old multiparous female Sumatran orangutan, held at Adelaide Zoo, Zoos SA (a Zoo and Aquarium Association [ZAA] accredited instituCorrespondence to: L. Johnson (e-mail: [email protected]). 0021-9975/$ - see front matter https://doi.org/10.1016/j.jcpa.2019.10.011
tion) gave birth to a single stillborn female infant, 2 weeks post her due date based on estimated conception date. She was found dead on arrival of keeping staff. Review of footage revealed that once the infant was born, she bled substantially and the placenta was not passed. Post-mortem examination revealed a placenta that was still completely adherent to the uterus. Gross examination revealed a placenta in situ implanted anteriorly over the body of the uterus. Histopathology showed several foci of placenta accreta with placental villi directly abutting the myometrium (Fig. 1a) and, in some places, invading the myometrium (Fig. 2). Maternal arteries supplying the placenta showed pregnancy-induced vascular changes; specifically, the musculo-elastic tissue that is normally present within the wall of these arteries when not pregnant was replaced by fibrinoid during pregnancy. Decidualization was seen in areas of the uterus away from the accreta (Fig. 1b). A 20-year-old nulliparous female chimpanzee, held at Monarto Zoo, Zoos SA (ZAA accredited Ó 2019 Elsevier Ltd. All rights reserved.
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Fig. 1. (a) Placenta accreta. Photomicrograph showing placental villi (some labelled as V) abutting directly onto the myometrium (M). HE. Bar, 100 mm. (b) Photomicrograph showing normal placental implantation with villi (V) implanting onto decidua (demarcated by D) that separates the villi from the myometrial layer (M). HE. Bar, 50 mm.
institution) gave birth to a single male infant 2 weeks earlier than her estimated due date based on swelling charts. She was found dead on arrival of keeping staff, lying near several pools of coagulated blood. The infant was a male that appeared to be of small birth weight and was adopted by a surrogate multiparous chimpanzee.
Post-mortem examination revealed a retained, adherent placenta implanted anteriorly over the uterine body wall. The clinical cause of death was ascribed to post-partum haemorrhage due to retained placenta, likely accreta. The placenta was particularly adherent to a thin diamond-shaped area of uterus (approximately 12 cm long and 5 cm wide) that measured approximately 8 mm in thickness. The remaining uterus was of normal thickness (approximately 20 mm). The thin area of uterus corresponded to an area of increased vascularization on the serosal uterine surface (Fig. 3). It took some manipulation to free the placenta from the uterine wall. There was an area of serosal haemorrhage on the right lateral aspect of the uterus, approximately 10 cm long and 1 cm wide. Multiple sections of uterine wall and placenta were sampled but, unfortunately, these did not include the placentaleuterine interface to enable a definitive histological diagnosis of placenta accreta to be made. However, histopathology revealed large arteries deep in the myometrium showing pregnancyinduced vascular changes (Fig. 4), in keeping with placenta accreta, as described above. The pathogenesis of placenta accreta involves overinvasiveness of the placenta or failure of normal decidualization (Khong, 2008). The degree of invasion allows the condition to be categorized histologically, according to severity, into placenta accreta, placenta increta and placenta percreta. Placenta accreta refers to placental adherence onto myometrium. Placenta increta, refers to deeper invasion, than placenta accreta, into the myometrium (Khong, 2008). Placenta percreta involves placental tissue invading the uterine wall entirely, passing through the serosa, where it may invade adjacent organs (Khong, 2008). A contemporary terminology refers to placenta accreta spectrum, which encompasses the adherent placenta (accreta) and the invasive placental disorders (increta and percreta) (Jauniaux et al., 2018b). Clinically, the placenta accreta spectrum is associated with difficulty removing the placenta from the uterine wall. Morphological changes in radial and arcuate arteries of the uterus render these large calibre vessels unable to vasoconstrict and, therefore, manual placental removal leads to catastrophic haemorrhage (Khong, 2008). Histologically, in normal placentation, the interface between placenta and myometrium is comprised of syncytial giant cells, the product of fused trophoblastic cells (Pijnenborg et al., 1981). A definitive histological diagnosis of placenta accreta is direct contact between the villous tissue of the placenta and underlying myometrium (Khong and Robertson, 1987). The trophoblasts do not fuse and
Placenta Accreta in an Orangutan and Chimpanzee
15
change phenotype (Khong and Robertson, 1987); this has important implications for clinical presentation, as giant cells are degenerate, but trophoblast cells retain invasive qualities required for early pregnancy (Khong, 2008). Trophoblasts undergo hypertrophy and hyperplasia, resulting in a thickened band at the uteroplacental interface (Khong and Robertson, 1987). In women, increased age, previous caesarean section, multiparity, high gravidity, previous curettage, female fetus, M€ ullerian (congenital) abnormalities and placenta praevia have all been defined as risk factors for placenta accreta (Khong and Robertson, 1987; Miller et al., 1997; Wu et al., 2005; Jauniaux et al., 2018b). It has also been suggested that trauma to the endometrium and consequent scarring may affect placentation (Miller et al., 1997; Jauniaux et al., 2018b). Further, it has been proposed that dehiscence of a scar in the uterine tissue may allow trophoblasts to invade deeper into the myometrium (Khong, 2008; Jauniaux et al., 2018b). It appears that in many, but not all cases, prior trauma to the uterus is considered part of the pathogenesis. Previous trauma or congenital abnormality of the uterus is most likely in the case of the chimpanzee.
Presenting prepartum symptoms are varied, depending on location and invasiveness of the accreta, but may include haemorrhage, pain or no symptoms (Makhseed and Moussa, 1995), as was the case for the orangutan and chimpanzee. Because the placenta fails to separate from the uterus, accretas are often associated with perinatal/post-partum haemorrhage in women (Miller et al., 1997). The volume of haemorrhage ranges from 2 to 20 l, and may lead to death by exsanguination (Abrams and Rutherford, 2011). Ultrasound is the procedure of choice for antenatal diagnosis of placenta accreta (Goh and Zalud, 2016). Sonographical diagnosis of placenta accreta spectrum disorders is excellent, with a sensitivity of 90.7% (Jauniaux et al., 2018a). Sonographical diagnosis is possible as early as 15 weeks, meaning it can be diagnosed at a routine scan (Comstock et al., 2004). Developing training methods for great apes, to be comfortable with more extensive sonographic examination, would be beneficial in managing this condition in these species. In one study of caesarean hysterectomy due to clinically suspected placenta accreta (i.e. intra-operative diagnosis), histological features necessary to confirm the diagnosis could not be identified in 52% of cases (Miller et al., 1997). Placenta accreta is largely a clinical manifestation when diagnosed peripartum, with retained placenta and/or manual removal signifying some degree of accreta to the physician (Dannheim et al., 2016). Clinical diagnosis and pathological diagnosis may be discordant depending on how strict the pathologist is with diagnostic criteria (Dannheim et al., 2016). Although there was no definitive histological evidence of placental villi in direct contact with myometrium due to lack of sampling of the uteroplacental interface in the chimpanzee, there were
Fig. 2. Placenta increta. Photomicrograph showing placental villi (V) invading into myometrium focally. HE. Bar, 100 mm.
Fig. 3. The uterus in situ. The left dorsolateral serosal surface of the uterus had extensive neovascularity over the serosal wall.
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Fig. 4. Photomicrograph of a maternal artery deep in the myometrium showing pregnancy-induced morphological changes indicating placenta accreta: the musculo-elastic tissue within the wall has been replaced by fibrinoid (arrows), leading to the inability of these large calibre vessels to vasoconstrict and limit blood flow after the placenta has been evacuated. HE. Bar, 200 mm.
two indications that the chimpanzee died from placenta accreta. Firstly, the thinned uterus with prominent serosal vessels is characteristic and secondly, the pregnancy-induced morphological changes in the large arteries deep in the myometrium indicate that there is placenta accreta; it is the latter feature that can give rise to bleeding significant enough to result in maternal death (Khong and Robertson, 1987; Khong, 2008). Thirdly, the placenta was not delivered and in conjunction with the above two factors and the large blood loss at delivery, the diagnosis of placenta accreta can be made clinically. The orangutan had both gross and histological confirmation of placenta accreta. In women, the treatment of choice for placenta accreta spectrum disorders, particularly the invasive forms, is caesarean hysterectomy (Goh and Zalud, 2016; Allen et al., 2018). A conservative approach is possible in many cases of accreta, but not in cases of increta or percreta. These approaches include use of potent uterotonic agents (e.g. oxytocin, misoprostol or carboprost), combined intrauterine and vaginal packing, and internal iliac arterial ligation (Makhseed and Moussa, 1995; Goh and Zalud, 2016; Sentilhes et al., 2018). These may be of use in a zoological setting with animals of high breeding value. It has been suggested that some primates are prone to developing post-partum haemorrhage due to their haemochorial placenta, which is the most invasive form of placentation (Abrams and Rutherford, 2011). This maximizes nutrient transfer, but may be
detrimental in predisposing the mother to placenta accreta and post-partum haemorrhage (Abrams and Rutherford, 2011). Even when compared with other haemochorial placental animals like monkeys, the hominoids (apes and human beings) have a more invasive placentation (Abrams and Rutherford, 2011; Carter and Pijnenborg, 2011; Pijnenborg et al., 2011; Crosley et al., 2013). Deep invasion by trophoblast cells and remodelling of maternal spiral arteries is believed to be beneficial for brain development during gestation (Carter and Pijnenborg, 2011). The placental biology of chimpanzees and women is very similar; they are often considered together: the ‘hominoid placenta’ (Carter and Pijnenborg, 2011). It is now reported that pre-eclampsia, which was thought to be a disease process unique to women, also occurs in chimpanzees (Baird, 1981; Thornton and Onwude, 1992; Crosley et al., 2013; Walter et al., 2018) and gorillas (Baird, 1981; Thornton and Onwude, 1992; Walter et al., 2018). One chimpanzee placental sample from a museum collection appeared to show endovascular invasion into a radial artery, which is unusual in women, except in cases of placenta accreta (Khong and Robertson, 1987; Pijnenborg et al., 2011). Placenta accreta is recognized as a common problem in human medicine, but has apparently not been reported previously in great apes. This may be due to underdiagnosis or placentas being eaten by the mother or other members of the troop. The pathogenesis is incompletely understood in women, but appears to involve either deep implantation, a failure of decidualization, or some combination of the two (Khong, 2008). The pathogenesis can be somewhat attributed to the anatomy of the human invasive haemochorial placenta (Abrams and Rutherford, 2011). There are wide family and species differences in the placenta and the maternal response to placentation among the non-human primates. Generally, the Prosimian suborder of primates lack a decidual reaction and only the family of Pongidae (apes) within the Anthropoid suborder of primates have both a decidual reaction and interstitial or deep implantation. It is therefore not unexpected that chimpanzees and orangutans would be susceptible to placenta accreta. Parenthetically, it is possible that the lack of decidual reaction and the superficial implantation in Old World monkeys such as the rhesus macaque (Macaca mulata) may be an additional reason why placenta accreta has not been reported in those animals, many more of whom are captive than the great apes. Indeed, the chimpanzee placenta may invade further into the myometrium than in women, in which case chimpanzees could theoretically be at higher risk
Placenta Accreta in an Orangutan and Chimpanzee
(Pijnenborg et al., 2011). More data on gross and histopathological anatomy of the great ape reproductive tract is required to better understand the risks and pathogenesis of reproductive disease in this species.
Conflict of Interest Statement The authors declare no conflict of interest with respect to the publication of this manuscript. This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profitsectors.
References Abrams ET, Rutherford JN (2011) Framing postpartum hemorrhage as a consequence of human placental biology: an evolutionary and comparative perspective. American Anthropology, 113, 417e430. Allen L, Jauniaux E, Hobson S, Papillon-Smith J, Belfort MA (2018) FIGO consensus guidelines on placenta accreta spectrum disorders: nonconservative surgical management. International Journal of Gynaecology & Obstetrics, 140, 281e290. Baird JN Jr. (1981) Eclampsia in a lowland gorilla. American Journal of Obstetrics and Gynecology, 141, 345e346. Carter AM, Pijnenborg R (2011) Evolution of invasive placentation with special reference to non-human primates. Best Practice Research in Clinical Obstetrics and Gynaecology, 25, 249e257. Comstock CH, Love JJ Jr., Bronsteen RA, Lee W, Vettraino IM et al. (2004) Sonographic detection of placenta accreta in the second and third trimesters of pregnancy. American Journal of Obstetrics and Gynecology, 190, 1135e1140. Crosley EJ, Elliot MG, Christians JK, Crespi BJ (2013) Placental invasion, preeclampsia risk and adaptive molecular evolution at the origin of the great apes: evidence from genome-wide analyses. Placenta, 34, 127e132. Dannheim K, Shainker SA, Hecht JL (2016) Hysterectomy for placenta accreta; methods for gross and microscopic pathology examination. Archives of Gynecology and Obstetrics, 293, 951e958. Goh WA, Zalud I (2016) Placenta accreta: diagnosis, management and the molecular biology of the morbidly adherent placenta. Journal of Maternal-Fetal and Neonatal Medicine, 29, 1795e1800. Jauniaux E, Bhide A, Kennedy A, Woodward P, Hubinont C et al. (2018a) FIGO consensus guidelines on placenta accreta spectrum disorders: prenatal diagnosis and screening. International Journal of Gynaecology & Obstetrics, 140, 274e280.
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Jauniaux E, Bunce C, Grønbeck L, Langhoff-Roos J (2019) Prevalence and main outcomes of placenta accreta spectrum: a systematic review and metaanalysis. American Journal of Obstetrics and Gynecology, 221, 208e218. Jauniaux E, Chantraine F, Silver RM, Langhoff-Roos J (2018b) FIGO consensus guidelines on placenta accreta spectrum disorders: epidemiology. International Journal of Gynaecology & Obstetrics, 140, 265e273. Khong TY (2008) The pathology of placenta accreta, a worldwide epidemic. Journal of Clinical Pathology, 61, 1243e1246. Khong TY, Robertson WB (1987) Placenta creta and placenta praevia creta. Placenta, 8, 399e409. Makhseed M, Moussa MA (1995) The outcome of placenta accreta in Kuwait (1981e1993). International Journal of Gynaecology & Obstetrics, 50, 139e144. Miller DA, Chollet JA, Goodwin TM (1997) Clinical risk factors for placenta previa-placenta accreta. American Journal of Obstetrics and Gynecology, 177, 210e214. Pijnenborg R, Bland JM, Robertson WB, Dixon G, Brosens I (1981) The pattern of interstitial trophoblastic invasion of the myometrium in early human pregnancy. Placenta, 2, 303e316. Pijnenborg R, Vercruysse L, Carter AM (2011) Deep trophoblast invasion and spiral artery remodelling in the placental bed of the chimpanzee. Placenta, 32, 400e408. Sentilhes L, Kayem G, Chandraharan E, PalaciosJaraquemada J, Jauniaux E (2018) FIGO consensus guidelines on placenta accreta spectrum disorders: conservative management. International Journal of Gynaecology & Obstetrics, 140, 291e298. Thornton JG, Onwude J (1992) Convulsions in pregnancy in related gorillas. American Journal of Obstetrics and Gynecology, 167, 240e241. Walter SL, Ali A, Killick R, Day C, Barrows M et al. (2018) Caesarean delivery of a Western Lowland gorilla with fetal distress and suspected pre-eclampsia. International Journal of Reproduction, Contraception, Obstetrics and Gynecology, 7, 2933e2936. Wu S, Kocherginsky M, Hibbard JU (2005) Abnormal placentation: twenty-year analysis. Amercian Journal of Obstetrics and Gynecology, 192, 1458e1461.
June 20th, 2019 ½ Received, Accepted, October 19th, 2019
Available online at www.sciencedirect.com
ScienceDirect www.elsevier.com/locate/jcpa
DISEASE IN WILDLIFE OR EXOTIC SPECIES
Placenta Accreta in an Oragnutan (Pongo abelii) and a Chimpanzee (Pan troglodytes) L. Johnson*, T. Y. Khong†, A. Rallis‡, L. Woolfordx, C. Brandǁ and I. Smith{ * Zoos SA, Monarto Zoo, Monarto, † SA Pathology, Women’s and Children’s Hospital, North Adelaide, ‡ Women’s Health Specialists, North Adelaide, x School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, ǁ Tea Tree Gully Veterinary Hospital, Tea Tree Gully and { Zoos SA, Adelaide Zoo, Adelaide
Summary Placenta accreta is defined as abnormal adherence of the placenta to the uterine wall. Placenta accreta is recognized as a common problem in human medicine, but has apparently not been reported previously in great apes, despite similarity in their reproductive biology. A 36-year-old multiparous female Sumatran orangutan (Pongo abelii) and a 20-year-old nulliparous female chimpanzee (Pan troglodytes), with gross uterine and histological uterine vascular changes that are characteristic of placenta accreta, are presented. Ó 2019 Elsevier Ltd. All rights reserved. Keywords: chimpanzee; orangutan; pathology; placenta accreta
Placenta accreta is defined as abnormal adherence of the placenta to the uterine wall (Khong, 2008). The prevalence in women was estimated to be 1 in 30,000 deliveries, prior to the recent increase in the use of caesarean section for deliveries, and in population studies published between 1982 and 2018 ranged between around 1 in 100 and 1 in 10,000 (Jauniaux et al., 2019). To the best of our knowledge, there are no reported cases of placenta accreta in orangutans (Pongo abelii), chimpanzees (Pan troglodytes) or other great apes. However, the reproductive biology of these species is strikingly similar to that of man (Carter and Pijnenborg, 2011; Pijnenborg et al., 2011; Crosley et al., 2013). Orangutans, chimpanzees and other great apes are likely to be susceptible to a similar range of reproductive complications, as recently reported for preeclampsia (Crosley et al., 2013). A 36-year-old multiparous female Sumatran orangutan, held at Adelaide Zoo, Zoos SA (a Zoo and Aquarium Association [ZAA] accredited instituCorrespondence to: L. Johnson (e-mail: [email protected]). 0021-9975/$ - see front matter https://doi.org/10.1016/j.jcpa.2019.10.011
tion) gave birth to a single stillborn female infant, 2 weeks post her due date based on estimated conception date. She was found dead on arrival of keeping staff. Review of footage revealed that once the infant was born, she bled substantially and the placenta was not passed. Post-mortem examination revealed a placenta that was still completely adherent to the uterus. Gross examination revealed a placenta in situ implanted anteriorly over the body of the uterus. Histopathology showed several foci of placenta accreta with placental villi directly abutting the myometrium (Fig. 1a) and, in some places, invading the myometrium (Fig. 2). Maternal arteries supplying the placenta showed pregnancy-induced vascular changes; specifically, the musculo-elastic tissue that is normally present within the wall of these arteries when not pregnant was replaced by fibrinoid during pregnancy. Decidualization was seen in areas of the uterus away from the accreta (Fig. 1b). A 20-year-old nulliparous female chimpanzee, held at Monarto Zoo, Zoos SA (ZAA accredited Ó 2019 Elsevier Ltd. All rights reserved.
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L. Johnson et al.
Fig. 1. (a) Placenta accreta. Photomicrograph showing placental villi (some labelled as V) abutting directly onto the myometrium (M). HE. Bar, 100 mm. (b) Photomicrograph showing normal placental implantation with villi (V) implanting onto decidua (demarcated by D) that separates the villi from the myometrial layer (M). HE. Bar, 50 mm.
institution) gave birth to a single male infant 2 weeks earlier than her estimated due date based on swelling charts. She was found dead on arrival of keeping staff, lying near several pools of coagulated blood. The infant was a male that appeared to be of small birth weight and was adopted by a surrogate multiparous chimpanzee.
Post-mortem examination revealed a retained, adherent placenta implanted anteriorly over the uterine body wall. The clinical cause of death was ascribed to post-partum haemorrhage due to retained placenta, likely accreta. The placenta was particularly adherent to a thin diamond-shaped area of uterus (approximately 12 cm long and 5 cm wide) that measured approximately 8 mm in thickness. The remaining uterus was of normal thickness (approximately 20 mm). The thin area of uterus corresponded to an area of increased vascularization on the serosal uterine surface (Fig. 3). It took some manipulation to free the placenta from the uterine wall. There was an area of serosal haemorrhage on the right lateral aspect of the uterus, approximately 10 cm long and 1 cm wide. Multiple sections of uterine wall and placenta were sampled but, unfortunately, these did not include the placentaleuterine interface to enable a definitive histological diagnosis of placenta accreta to be made. However, histopathology revealed large arteries deep in the myometrium showing pregnancyinduced vascular changes (Fig. 4), in keeping with placenta accreta, as described above. The pathogenesis of placenta accreta involves overinvasiveness of the placenta or failure of normal decidualization (Khong, 2008). The degree of invasion allows the condition to be categorized histologically, according to severity, into placenta accreta, placenta increta and placenta percreta. Placenta accreta refers to placental adherence onto myometrium. Placenta increta, refers to deeper invasion, than placenta accreta, into the myometrium (Khong, 2008). Placenta percreta involves placental tissue invading the uterine wall entirely, passing through the serosa, where it may invade adjacent organs (Khong, 2008). A contemporary terminology refers to placenta accreta spectrum, which encompasses the adherent placenta (accreta) and the invasive placental disorders (increta and percreta) (Jauniaux et al., 2018b). Clinically, the placenta accreta spectrum is associated with difficulty removing the placenta from the uterine wall. Morphological changes in radial and arcuate arteries of the uterus render these large calibre vessels unable to vasoconstrict and, therefore, manual placental removal leads to catastrophic haemorrhage (Khong, 2008). Histologically, in normal placentation, the interface between placenta and myometrium is comprised of syncytial giant cells, the product of fused trophoblastic cells (Pijnenborg et al., 1981). A definitive histological diagnosis of placenta accreta is direct contact between the villous tissue of the placenta and underlying myometrium (Khong and Robertson, 1987). The trophoblasts do not fuse and
Placenta Accreta in an Orangutan and Chimpanzee
15
change phenotype (Khong and Robertson, 1987); this has important implications for clinical presentation, as giant cells are degenerate, but trophoblast cells retain invasive qualities required for early pregnancy (Khong, 2008). Trophoblasts undergo hypertrophy and hyperplasia, resulting in a thickened band at the uteroplacental interface (Khong and Robertson, 1987). In women, increased age, previous caesarean section, multiparity, high gravidity, previous curettage, female fetus, M€ ullerian (congenital) abnormalities and placenta praevia have all been defined as risk factors for placenta accreta (Khong and Robertson, 1987; Miller et al., 1997; Wu et al., 2005; Jauniaux et al., 2018b). It has also been suggested that trauma to the endometrium and consequent scarring may affect placentation (Miller et al., 1997; Jauniaux et al., 2018b). Further, it has been proposed that dehiscence of a scar in the uterine tissue may allow trophoblasts to invade deeper into the myometrium (Khong, 2008; Jauniaux et al., 2018b). It appears that in many, but not all cases, prior trauma to the uterus is considered part of the pathogenesis. Previous trauma or congenital abnormality of the uterus is most likely in the case of the chimpanzee.
Presenting prepartum symptoms are varied, depending on location and invasiveness of the accreta, but may include haemorrhage, pain or no symptoms (Makhseed and Moussa, 1995), as was the case for the orangutan and chimpanzee. Because the placenta fails to separate from the uterus, accretas are often associated with perinatal/post-partum haemorrhage in women (Miller et al., 1997). The volume of haemorrhage ranges from 2 to 20 l, and may lead to death by exsanguination (Abrams and Rutherford, 2011). Ultrasound is the procedure of choice for antenatal diagnosis of placenta accreta (Goh and Zalud, 2016). Sonographical diagnosis of placenta accreta spectrum disorders is excellent, with a sensitivity of 90.7% (Jauniaux et al., 2018a). Sonographical diagnosis is possible as early as 15 weeks, meaning it can be diagnosed at a routine scan (Comstock et al., 2004). Developing training methods for great apes, to be comfortable with more extensive sonographic examination, would be beneficial in managing this condition in these species. In one study of caesarean hysterectomy due to clinically suspected placenta accreta (i.e. intra-operative diagnosis), histological features necessary to confirm the diagnosis could not be identified in 52% of cases (Miller et al., 1997). Placenta accreta is largely a clinical manifestation when diagnosed peripartum, with retained placenta and/or manual removal signifying some degree of accreta to the physician (Dannheim et al., 2016). Clinical diagnosis and pathological diagnosis may be discordant depending on how strict the pathologist is with diagnostic criteria (Dannheim et al., 2016). Although there was no definitive histological evidence of placental villi in direct contact with myometrium due to lack of sampling of the uteroplacental interface in the chimpanzee, there were
Fig. 2. Placenta increta. Photomicrograph showing placental villi (V) invading into myometrium focally. HE. Bar, 100 mm.
Fig. 3. The uterus in situ. The left dorsolateral serosal surface of the uterus had extensive neovascularity over the serosal wall.
16
L. Johnson et al.
Fig. 4. Photomicrograph of a maternal artery deep in the myometrium showing pregnancy-induced morphological changes indicating placenta accreta: the musculo-elastic tissue within the wall has been replaced by fibrinoid (arrows), leading to the inability of these large calibre vessels to vasoconstrict and limit blood flow after the placenta has been evacuated. HE. Bar, 200 mm.
two indications that the chimpanzee died from placenta accreta. Firstly, the thinned uterus with prominent serosal vessels is characteristic and secondly, the pregnancy-induced morphological changes in the large arteries deep in the myometrium indicate that there is placenta accreta; it is the latter feature that can give rise to bleeding significant enough to result in maternal death (Khong and Robertson, 1987; Khong, 2008). Thirdly, the placenta was not delivered and in conjunction with the above two factors and the large blood loss at delivery, the diagnosis of placenta accreta can be made clinically. The orangutan had both gross and histological confirmation of placenta accreta. In women, the treatment of choice for placenta accreta spectrum disorders, particularly the invasive forms, is caesarean hysterectomy (Goh and Zalud, 2016; Allen et al., 2018). A conservative approach is possible in many cases of accreta, but not in cases of increta or percreta. These approaches include use of potent uterotonic agents (e.g. oxytocin, misoprostol or carboprost), combined intrauterine and vaginal packing, and internal iliac arterial ligation (Makhseed and Moussa, 1995; Goh and Zalud, 2016; Sentilhes et al., 2018). These may be of use in a zoological setting with animals of high breeding value. It has been suggested that some primates are prone to developing post-partum haemorrhage due to their haemochorial placenta, which is the most invasive form of placentation (Abrams and Rutherford, 2011). This maximizes nutrient transfer, but may be
detrimental in predisposing the mother to placenta accreta and post-partum haemorrhage (Abrams and Rutherford, 2011). Even when compared with other haemochorial placental animals like monkeys, the hominoids (apes and human beings) have a more invasive placentation (Abrams and Rutherford, 2011; Carter and Pijnenborg, 2011; Pijnenborg et al., 2011; Crosley et al., 2013). Deep invasion by trophoblast cells and remodelling of maternal spiral arteries is believed to be beneficial for brain development during gestation (Carter and Pijnenborg, 2011). The placental biology of chimpanzees and women is very similar; they are often considered together: the ‘hominoid placenta’ (Carter and Pijnenborg, 2011). It is now reported that pre-eclampsia, which was thought to be a disease process unique to women, also occurs in chimpanzees (Baird, 1981; Thornton and Onwude, 1992; Crosley et al., 2013; Walter et al., 2018) and gorillas (Baird, 1981; Thornton and Onwude, 1992; Walter et al., 2018). One chimpanzee placental sample from a museum collection appeared to show endovascular invasion into a radial artery, which is unusual in women, except in cases of placenta accreta (Khong and Robertson, 1987; Pijnenborg et al., 2011). Placenta accreta is recognized as a common problem in human medicine, but has apparently not been reported previously in great apes. This may be due to underdiagnosis or placentas being eaten by the mother or other members of the troop. The pathogenesis is incompletely understood in women, but appears to involve either deep implantation, a failure of decidualization, or some combination of the two (Khong, 2008). The pathogenesis can be somewhat attributed to the anatomy of the human invasive haemochorial placenta (Abrams and Rutherford, 2011). There are wide family and species differences in the placenta and the maternal response to placentation among the non-human primates. Generally, the Prosimian suborder of primates lack a decidual reaction and only the family of Pongidae (apes) within the Anthropoid suborder of primates have both a decidual reaction and interstitial or deep implantation. It is therefore not unexpected that chimpanzees and orangutans would be susceptible to placenta accreta. Parenthetically, it is possible that the lack of decidual reaction and the superficial implantation in Old World monkeys such as the rhesus macaque (Macaca mulata) may be an additional reason why placenta accreta has not been reported in those animals, many more of whom are captive than the great apes. Indeed, the chimpanzee placenta may invade further into the myometrium than in women, in which case chimpanzees could theoretically be at higher risk
Placenta Accreta in an Orangutan and Chimpanzee
(Pijnenborg et al., 2011). More data on gross and histopathological anatomy of the great ape reproductive tract is required to better understand the risks and pathogenesis of reproductive disease in this species.
Conflict of Interest Statement The authors declare no conflict of interest with respect to the publication of this manuscript. This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profitsectors.
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June 20th, 2019 ½ Received, Accepted, October 19th, 2019