Anti-Müllerian Hormone Profiles as a Novel Biomarker to Diagnose Granulosa-theca Cell Tumors in Cattle

Abstract

Abstract. This study was carried out to evaluate the blood profile and tissue expression of Anti-Müllerian hormone (AMH) as a biomarker for granulosa-theca cell tumors (GTCTs) in cattle. Five cases with unilateral ovarian GTCTs (GTCT group) were investigated in comparison to other groups of Japanese Black cows, which had either cystic ovarian disease (COD group, n=5), a functional corpus luteum on Days 9 to 11 of the estrous cycle (Day 0=estrus; CL group, n=13) or received superovulation treatment (SOT group, n=13). We used transrectal ultrasonography and measured plasma AMH, estradiol-17β (E 2 ), progesterone (P 4 ) and testosterone (T) levels. Moreover, GTCT tissues were collected and examined by immunohistochemical staining (IHC) for AMH. In the GTCT group, ultrasound images of GTCTs were variable and not definitive. However, the AMH level in the GTCT group (n=3, 58.1 ± 66.3 ng/ml) was significantly higher than in the COD, CL and SOT groups (0.1 ± 0.1 ng/ml for GTCT vs. COD, P<0.05; 0.2 ± 0.1 and 0.3 ± 0.2 ng/ml, respectively for GTCT vs. CL and SOT, P<0.01). The other hormonal levels in the GTCT group had no significant differences compared with the COD or SOT group. Neoplastic granulosa cells labeled with AMH antibody clearly demonstrated a variety of tissue patterns in all cases by IHC. To the best of our knowledge, this is the first study to investigate the blood profile and IHC of AMH in bovine GTCTs. Our findings indicate that AMH may be a novel biomarker to diagnose GTCTs in cattle. Key words: Anti-Müllerian hormone (AMH), Cattle, Granulosa-theca cell tumors (GTCTs), Immunohistochemical staining (J. Reprod. Dev. 58: [98][99][100][101][102][103][104] 2012) G ranulosa-theca cell tumors (GTCTs) are the most common ovarian tumors in cattle [1], and the incidence may be less than 0.5% [2]. GTCTs can affect various breeds [3] and occur at various ages [4] in cattle. GTCTs produce a variety of steroid hormones, causing a subsequent elevation of plasma estradiol-17β (E 2 ), progesterone (P 4 ) and/or testosterone (T) levels [4]. Therefore, a variety of clinical signs, such as nymphomania [5], virilism [6] and mammary gland development [7], could be presented. In contrast, some in GTCTs may not result in abnormal reproductive behavior at all [3]. Preliminary diagnosis of GTCTs can be achieved by transrectal palpation and ultrasonography [1,4]. GTCTs should be suspected if a chronic cystic ovarian disease (COD) does not respond to standard treatment regimens or if the diameter of the ovary is more than 100 mm [1]. Thus, GTCTs should be distinguished from other conditions, such as COD, oophoritis, ovarian abscesses and parovarian cysts, by these clinical signs [8]. However, the distinctions might be difficult depending on the clinical signs and other diagnostic methods, so a definitive diagnosis can only be made based on histopathological examination of the affected ovary [3]. In the treatment of unilateral bovine GTCTs, unilateral ovariectomy is only indicated in cows that do not exhibit alterations in secon...

Clinical diagnosis of bovine granulosa cell tumour in a Holstein cow using plasma anti-Müllerian hormone concentration: a case report

“…GCTs have been reported with various parities and reproductive statuses, with the variation in weights and sizes of the affected ovaries (Kikuchi et al 1995;Meganck et al, 2010;Kitahara et al 2012). Moreover, ultrasonography of GCTs also showed various appearances.…”

“…Cows with GCTs may show nymphomania and abnormal udder development (Leder et al 1988) or may not show any clinical signs (Zachary and Haliburton 1983;Inokuma et al 2006;Haneishi et al 2008). The GCTs are generally unilateral, and the contralateral ovary is frequently small and inactive due to the cessation of oestrus cycle activity (Kumamoto et al 1998;Meganck et al 2010;Kitahara et al 2012). Proper diagnosis of GCTs might be difficult in the field-level examinations, such as rectal palpation and ultrasonography (Zulu et al 2000;Masseau et al 2004;Meganck et al 2010;Kitahara et al 2012).…”

“…The GCTs are generally unilateral, and the contralateral ovary is frequently small and inactive due to the cessation of oestrus cycle activity (Kumamoto et al 1998;Meganck et al 2010;Kitahara et al 2012). Proper diagnosis of GCTs might be difficult in the field-level examinations, such as rectal palpation and ultrasonography (Zulu et al 2000;Masseau et al 2004;Meganck et al 2010;Kitahara et al 2012). The disease has to be distinguished from ovarian cyst, oophoritis and ovarian abscesses (Zulu et al 2000;Kitahara et al 2012).…”

“…Proper diagnosis of GCTs might be difficult in the field-level examinations, such as rectal palpation and ultrasonography (Zulu et al 2000;Masseau et al 2004;Meganck et al 2010;Kitahara et al 2012). The disease has to be distinguished from ovarian cyst, oophoritis and ovarian abscesses (Zulu et al 2000;Kitahara et al 2012). Thus, upon tentative diagnosis, ovariectomy has been performed to definitive diagnosis based on histopathological examination of the ovarian tissues (Leder et al 1988;Haneishi et al 2008).…”

“…However, recently, in mares, it was found that the sensitivity of anti-Müllerian hormone (AMH) for detection of GCTs was significantly higher than that of either inhibin or testosterone (Ball et al 2013). Similarly, in cattle, the measurement of plasma AMH concentration was identified as a more reliable and sensitive method to diagnose GCTs than that of the measurement of INH or ovarian steroids (Kitahara et al 2012). The cut-off diagnostic concentration of plasma AMH in GCTsaffected cattle is identified as >0.36 ng/ml (El-Sheikh Ali et al 2013).…”