Ovary in hernia sac: Prolapsed or a descended gonad?

Ovary in Hernia Sac: Prolapsed or a Descended Gonad? By H. bzbey,

M. Ratschek,

G. Schimpl, Graz,

Background/Purpose: The ligament that lies in the inguinal hernia sac of girls IS known to be the round ligament and is described as homologous to the male gubernaculum. An ovary in a hernia sac might be assumed to mimic descent of the testis. The aim of this study is to determine whether this ligament has a role in final ovarian position. Methods: Samples ment were obtained underwent inguinal evaluated through analyses.

of peritoneal tissues containing the ligafrom 15 female infants and children who hernia repair. Tissue specimens were histopathologic and immunohistological

Resu/ts:The ligament consists of striated and smooth muscle fibers, abundant nerves, and vessels. Estrogen receptors (ER) and progesterone receptors (PR) were identified in submesothelial stromal and smooth muscle cells. No androgen receptors (AR) were found.

A

LTHOUGH MOST of them are purely hypothetical, many theories have been proposed to describe the mechanisms controlling the final position of the testis.’ Among the gubernaculum, processus vaginalis, inguinal canal, spermatic vessels, and scrotum, it is widely accepted that the gubernaculum “holds the key” to the mystery of testicular descent. However, within the mass movement of testis, epididymis, and gubernaculum through the inguinal canal, the presence of the processus vaginalis and its gonadal attachments have received less attention.2,3 In this study, the ovary in a hernia sac is assumed as homologous to descent of the testis, and OUT aim is to determine whether the ligament that terminates in the processus vaginalis of a female inguinal hernia has a role in final ovarian position. MATERIALS

AND

METHODS

Samples of peritoneal tissues containing the ligament were obtamed from 15 girls aged 1 month to 9 years (mean, 49 +- 3 1.5 months) during routine inguinal hernia repair. The hernia sac was grasped, lifted with clamps, and opened on the thinner anteromedial side without damage to the ligament present on the posterolateral site. Proximally. the fibres of the ligament were found in contact to the distal fallopian tube and ovary, spreading in a fanIike fashion in the hernia sac distally (Fig 1). The resected hernia sac was evaluated through histopathologic and immunohistological analyses. For standard histological examination. sections were stained with H&E. Nuclear staining observed m sections incubated with the androgen receptor (AR), estrogen receptor (ER), or progesterone receptor (PR) antibodies (monoclonal antiandrogen receptor, code:MCR205, Ylem Co; monoclonal antiestrogen receptor:ERLH2. code.MCR206, Ylem Co: monoclonal antlprogesterone receptor, code:MCRZOZ, Ylem Co; Rome, Italy) were defined as AR-, ER- or JournalofPediatric

Surgery,

Vol 34, No 6 (June),

1999: pp 977-980

and

M.E.

Hiillwarth

Austria

Conclusions: Although its termination in the processus vaginalis is not found to be consistent with the classical description of the round ligament, localization of ERs and PRs prove that the ligament is a target organ influenced by hormones. Because the round ligament is supposed to be the female gubernaculum that has an altered anatomy and localization because of absence of androgen responsiveness, its modified presentation in a processus vaginalis raises the suspicion that the ovary in a hernia sac may not simply be prolapsed, but is a descended gonad. J Pediatr Surg 34:977-980. Copyright o 1999 by W.B. Saunders Company.

INDEX WORDS: lum, testicular

lnguinal descent.

hernia,

round

ligament,

gubernacu-

PR-positive mmunohistologlcal staming. The smooth muscle were demonstrated with an antibody to al-smooth muscle (monoclonal anti-oc-smooth muscle actin; Sigma, St Louis, MO).

cells actm

RESULTS

In all patients, the ligament that ran along the inner aspect of the hernia sac ended in the processus vaginalis in a fanlike fashion. Complete hemiation of the ovary into the hernia sac was observed in two patients, and gentle traction on the ligament brought into view the fallopian tube and the ovary in the remaining 13 patients. On histological examination, it was found that this ligament consisted of striated and smooth muscle fibers, abundant nerves, and vessels (Fig 2). In some specimens, swirls of nerves and vessels were observed within the meshwork of the ligament. Immunostaining showed a weak to moderate nuclear reactivity of the submesothelial stromal cells and groups of smooth muscle cells with antibodies to estrogen and progesterone receptors (Fig 3). No reactivity could be obtained with an antibody to testosterone receptors.

From the Departments of Pediatric Surgery and Pathology, University of Graz, Medical School, Graz, Austria. This study was partly supported by Austmw Academic Exchange Serwce, Wlen, Austria. Address reprint requests to Htiseyin Ozbey, MD, Department oj Pediatric Surgeq, University of Istanbul, Istanbul Medical Facultl: 34390, Capa, Istanbul, Turkey. Copyright o 1999 by WB. Saunders Company 0022.3168/99/3406-0011$03.00/0 977

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Fig 1.

The ligament

that lies in the hernia

ET AL

sac of girls.

DISCUSSION

The ligament, which lies in inguinal hernia sac of girls, is known to be the round ligament.4 Recently, the anatomic description of this ligament is made with the conclusion that it may not be the round ligament of the uterus, but the suspensory ligament of the o~ary.~ However, there are inconsistencies in the description of the

Fig 3. (Al ER and (BI PR nuclear immunostaining of the submesothelial stromal cells (straight arrow) and smooth muscle cells (angled arrow1 of the ligament.

Fig 2. Hematoxylin and eosin-stained sections of the processus vaginalis. The meshwork of the ligament is shown to be composed of mesothelium, smooth muscle fibers, vessels and nerves (A), striated and smooth muscle, bundles of nerves, and arteries (B). (Arrow denotes peritoneal surface.)

nature of the suspensory ligament of the ovary, the round ligament, and the normal anatomic relationships of the ovaries between humans and other mammals6 The round ligament in a female fetus has been described as homologous to the gubernaculum of the testis, whereas the ligament of the ovary corresponds to a connection between the testis and epididymis, which shortens and disappears at an early period in the male fetus’ (Fig 4). However, in patients with persistent miillerian duct syndrome (PMDS), there is conspicious absence of the round ligaments, despite persistence of the mtillerian ducts. The testes usually are extremely mobile and ovarian in position, attached to an elongated and attenuated “round ligament” or feminized gubernaculum in the processus vaginalis (Fig 5). It was postulated that the main anomaly in unstable gonadal position is failure of the gubernaculum to be masculinized so that it remains long and thin, analogous to the round ligament.7-9 Thus, the predominant effect of either the gubernaculum or cranial suspensory ligament seems to be responsible for the final gonadal position. The most common accepted theory in testicular descent is the biphasic model in which each phase is controlled by different anatomic and hormonal mecha-

OVARY

IN HERNIA

NORMAL

SAC

MALE

Fig 4. Schema illustrates the final position sus vaginalis, and the gubernaculum in normal

979

NORMAL

FEMALE

of the gonad, procesboys and girls.

nisms.lOJ1Enlargement of the gubemaculum in response to miillerian-inhibiting substance (MIS) and its migration under the influence of testosterone were suggested as the transabdominal and inguinoscrotal phases of testicular descent, respectively. Androgen receptors have been found in the gubemaculum of fetal rats and also are identified in the lumbar spinal cord a day before the onset of maximal androgenic action for testicular descent.i2-I4 Cryptorchidism and persistence of the cranial gonadal ligament has been shown in male rat fetuses exposed to antiandrogen. i5.i6 However, because of cryptorchidism

FEMALE (MGUINAI- tiE!‘JJiA

Fig 5. (A) Ovarian position in female inguinal hernia and IB) the highly mobile gonad in patients with PMDS, gonadal dysgenesis, or patients with ovotestis.

observed in male offsprings of estrogen-treated pregnant mice, it was postulated that estrogen may interfere with androgen secretion or with the action of MIS.i7J8 In female rats, clear indications were obtained that ovaries ascend, together with the ascending kidneys, under the influence of the developing cranial ovarian suspensory ligaments. l5 In a recent study, partial descent of the fetal ovaries could be observed in androgen-treated timed-pregnant mice.19 Recent findings of ER in specific components of the female external genitalia suggested that there may be more than one mechanism responsible for female phenotypic differentiation of external genitalia, which is contrary to the concept of “passive” female external genital development.zo~‘l It is evident that besides sexual differentiation, migration of the gonad to its final location requires a cascade of complex molecular and morphological events occurring at appropriate times and in the correct sequence. Knowing that the primordial structures of the internal genitalia suspensory structures show sexual dimorphism and the gonadal migration is a steroid hormone-mediated process, the cessation of migration might be related to regulation at the tissue receptor level. Although it connects the internal genital system to the inguinal abdominal wall in both sexes, attention to the development and function of the processus vaginalis, especially the ligament found in hernia sac of girls, is virtually absent. 22,23The usual finding of a processus vaginalis in boys with undescended testis and its persistence in cases with ascending testis support the theory that luminal narrowing and closure of processus vaginalis may be prevented by some hormonal factorsz41z5Calcitonin gene-related peptide (CGRP), released from the genitofemoral nerve, has been proposed to be responsible for the failure of its fusion and disappearance.26 Anatomically, both the gubemaculum testis and the (doubtfully called) round ligament of the uterus are innervated by the genitofemoral nerve, making control of closure of the processus vaginalis possible in both sexes by this mechanism. It has been shown that prenatal administration of flutamide, a potent antiandrogen, causes significant inhibition in growth of the processus vaginalis, associated with cryptorchidism. 27Epididymal abnormalities, which usually are correlated with undescended testis, are more closely related to the presence of a patent processus vaginalis with a hernia or hydrocele.28x2g Hence, the patency of the processus vaginalis should be questioned together with the enigmatic features of the suspensory struchtres of the internal genitalia and the final gonadal position. In 21% of girls with inguinal hernia, the fallopian tube, occasionally with the ovary or uterus, lies in the wall of the hernia sac.4 Although complete hemiation of the ovary into the hernia sac was observed in only two of our patients, in the remaining 13 patients. the fallopian tube

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and ovary could be brought out when a gentle traction is applied to the ligament. This observation confirms that, whether it has passed the internal ring or not, the ovary lies in a lower pelvic or inguinal position in children with inguinal hernia. Unlike the observations of Ando et a1,5 we could not see any other ligament that could be mentioned as the round ligament in dissections during the inguinal hernia repair. Our findings also confirm the findings that the (doubtfully called) round ligament fails to reach the labium majorum.23 The presence of striated and smooth muscle fibers, nerves, and vessels and the steroid receptors in the studied ligament are in contrast with the known features of both the suspensory ligament of the ovary and the round ligament.6~22~23,30,3r Hence, any term among the present nomenclature may not indicate the ligament in

ET AL

female hernia sac when the functional, anatomic, and histopathologic features are taken into account. This is the first study evaluating the histopathologic structure and presence of steroid hormone receptors in the ligament that lies in the inguinal hernia sac of girls. Because the round ligament is supposed to be the female gubemaculum, which has an altered anatomy and localization because of absence of androgen responsiveness, its modified presentation in the processus vaginalis raises the suspicion that the ovary in a hernia sac simply may not be prolapsed, but represents a descended gonad. Further studies focused on this mesorchium are needed. ACKNOWLEDGMENT The authors thank Dr Pieter van der Schoot (Utrecht. Holland) for his assistance with the mterpretatron of the histology and for the comments.

REFERENCES 1. Heyns CF, Hutson JM: Historical review of theories on testicular descent. J Urol 153:754-767. 1995 2. Backhouse KM: Embryology of the normal and cryptorchid testis, in Fonkalsrud EW, Mengel W, (eds): The Undescended Testis. Chmago. IL, Year Book Medical Publishers. 1981, pp 5-29 3. van der Schoot, Vigrer B, Prepin J, et al: Development of the gubemaculum and processus vaginalis in freemartinism: Further evidence in support of a specific fetal testis hormone governing malespecific gubemacular development. Anat Ret 241:211-224, 1995 4. Lloyd DA, Rintala RJ: Inguinal hernia and hydrocele, in O’Neill JA Jr, Rowe MI, Grosfeld JL, et al (eds): Pediatric Surgery, Vo12 (ed 5) St Louis, MO, Mosby-Year BookInc, 1998. pp 1071-1086 5. Ando H, Kaneko K. Ito F, et al: Anatomy of the round ligament in female infants and children with an inguinal hernia. Br J Surg 84:404-405, 1997 6. van der Schoot P: The name cranial ovarian suspensory ligaments in mammalian anatomy should be used only to indicate the structures derived from the foetal cranial mesonephric and gonadal ligaments. Anat Ret 237:434-438, 1993 7. Hutson JM, Chow CW, Ng WD: Persistent mttllerian duct syndrome with transverse testicular ectopia. Pediatr Surg Int 2:191-194, 1987 8. Hutson JM, Baker ML: A hypothesis to explain abnormal gonadal descent in persistent miillerian duct syndrome. Pediatr Surg Int 9:542543,1994 9. Hutson JM, Davidson PM. Reece LA, et al: Failure of gubernacular development in the persistent mtillerian duct syndrome allows hemiation of the testes. Pediatr Surg Int 9:544-546, 1994 10. Hutson JM: A biphasic model for the hormonal control of testtcular descent. Lancet 24:419-421, 1985 11. Clamette TD. Sugita Y, Hutson JM: Genital anomalies in human and animal models reveal the mechanisms and hormones governing testicular descent. Br J Ural 79:99-l 12, 1997 12. Husmann DA, McPhaul MJ: Time-specific androgen blockade with flutamide inhibits testicular descent in the rat. Endocrinology 129:1409-1416. 1991 13. Heyns CF, Pape VC: Presence of low capacity androgen receptor inthegubemaculumofthepigfetus. JUrol 145:161-167, 1991 14. Bentvelsen FM, George Fw: The fetal rat gubemaculum contains higher levels of androgen receptor than does the postnatal gubemaculum. J Urol1.50:1564-1566,1993 15. van der Schoot P: Doubts about the ‘first phase of testis descent’ in the rat as avahd concept. Anat Embryo1 187:203-208, 1993 16. van der Schoot P, Elger W: Androgen-induced failure of the outgrowth of the cranial gonadal suspensory ligaments m foetal rats. J Androl 13:534-542, 1992

17. Hadziselimovic F: Cryptorchidism Management and Implications. Berlin, Germany, Springer, 1983 18. Luthra M, Hutson JM: Late-gestation exogenous oestrogen inhibits testicular descent in fetal mice despite Mtillerian duct regresston. Pediatr Surg Int 4:260-264, 1989 19. Lee SMY, Hutson JM: The effects of androgens on the cramal suspensory ligament and ovarian position. Presented at the BAPS XLIV Annual International Congress, Istanbul. Turkey, July 22-25. 1997 20. Jost A, Prepin J, Vigier B: Hormones m the morphogenesis of the genital system, in Blandau RJ, Bergsma D, (eds): Morphogenesis and Malformation of the Genital System. National Foundation-March of Dimes Birth Defects Orig Art Ser Vol13. New York, NY, Liss, 1977, pp 12-33 21. Kalloo NB, Gearhart JP, Barrack ER: Sexually dimorphic expression of estrogen receptors, but not of androgen receptors in human fetal external genitalia. J Clin Endocrinol Metab 77:692-698, 1993 22. van der Schoot P: Human (and some other primates’) uterine teres ligament represents a mammalian developmental novelty. Anat Ret 244:402-415,1996 23. Attah AA. Hutson JM: The anatomy of the female gubemaculum is different from the male. Austr N Z J Surg 61:380-384, 1991 24. Donnell SC, Rickwood AMK. Jee LD. et al: Congenital testicular maldescent: Significance of the complete hernial sac. Br J Urol 75:702-703, 1995 25. Clarnette TD, Hutson JM: The genitofemoral nerve may link testicular inguinoscrotal descent with congenital inguinal hernia. Aust N Z J Surg 66:612-617. 1996 26. Clarnette TD, Rowe DR, Hasthorpe S. et al: Incomplete disappearance of the processus vaginalis as a cause of ascending testis. J Urol 157:1889-1891. 1997 27. Shono T, Ramm-Anderson S. Goh DW, et al: The effects of flutamide on testicular descent in rats examined by scanning electron microscopy. J Pediatr Surg 29:839-844. 1994 28. Rozanskr TA, Bloom DA: The undescended testis: Theory and management. Urol Clin North Am 22107-118, 1995 29. Elder JS: Epididymal anomalies associated with hydrocele/ hernia and cryptorchidrsm: Implications regarding testicular descent. J Urol 148:624-626, 1992 30. Smith P, Heimer G, Norgren A, et al: Steroid hormone receptors in pelvic muscles and ligaments in women. Gynecol Obstet Invest 30:27-30.1990 3 1. Smith P, Heimer G, Norgren A, et al: The round ligament: A target organ for steroid hormones. Gynecol Endocrinol7:97-100, 1993