JUXTAGONADAL MESONEPHRIC GLOMERULI IN FETUSES OF 11 TO 21 WEEKS OF GESTATION

Calvin E. Oyer, MD Brown University School of Medicine, Providence, Rhode Island 02905

0 Department of Pathology, Women and Infants’ Hospital and

Mesonephric glomeruli and tubules were found in the juxtagonadal region in I1 fetuses ranging in age from I 1 to 21 postmenstrual weeks. Although mesonephric excretory function into the fourth month o j

gestaiion has been postulated, mesonephric glomeruli have been previous(y acknowledged anatomically only during embryonal and early fetal l i f e The present observations indicate that mesonephric glomeruli persist as anatomical structures into the midtrimester of gestation. The conclusion that the observed glomeruli are mesonephric is based on their location and the known strong anatomical and functional ties that bind mesonephros and gonad during development.

KEY WORDS: fetus, genitourinary anomalies, glomeruli, gonad, mesonephros, ectopic renal tissue

INTRODUCTION

This report concerns the observation of juxtagonadal mesonephric glo- meruli, in 1 1 fetuses of 11-21 weeks of gestation. The mesonephros, a transient organ of embryonal and early fetal life, is usually described as an interim kid- ney in humans, preceded by a nonfunctional rudimentary pronephros and sup- planted by the definitive kidney, the metanephros (1). Willis (2), however, states that these three structures “are not separate organs, but merely three arbitrary regions in a continuous nephrogenic cord.” Support for this unitary concept has recently been thoroughly discussed from a historical standpoint by Aterman (3). Whether it is a separate organ or the midportion of a holonephros, the me- sonephros appears late in the fourth developmental week, develops, and then degenerates in a craniocaudal sequence, leaving persistent tubules to form effer- ent ductules in males and occasionally a paradidymis in the male or an epooph- oron and/or a paroophoron in the female (1). Willis (2) noted that “in the second half of the second month, . . . all the mesonephric glomeruli and most of the tubules undergo atrophy in craniocaudal order, until finally there are left only the tubules in the close vicinity of the gonad.” Moore in his second edition (4) states that by the beginning of the fetal period (ninth developmental week)

The author wishes to acknowledge encouragement and helpful criticism from Don B. Singer, M.D.

Address reprint requests to Calvin E. Oyer, M.D., Department of Pathology, Women and Infants’ and Beverly B. Rogers, M.D., Providence, Rhode Island.

Hospital, 101 Dudley St., Providence, Rhode Island 02905.

Pediatric PathoLou, 12: 683-689, I992 Copyright @ I992 by Hemisphere Publishing Corporation

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“most of the mesonephros has degenerated and disappeared, except for its duct and a few tubules which persist. . . .” According to Arey (5), degeneration is not complete until the end of the fourth month, but he made no reference to the persistence of glomeruli. Although the mesonephros is thought to perform ex- cretory function in the human embryo from the fourth week to the fourth month (4), in none of the literature cited above is there a reference to anatomi- cally demonstrated persisting mesonephric glomeruli. De Martino et al. studied mesonephric glomeruli by light and electron microscopy in embryos of 7 and 10 weeks (6) and “a 12-week-old female embryo (sic)” (7). They regard the me- sonephros as “the primary excretory organ of the embryo during the period from the fourth week to the fourth month” but have not reported the persis- tence of glomeruli later than those dates cited above. Others (1, 8) also accept the mesonephros as a transiently functioning organ in humans, but Starck (9) concluded that, although present, it is nonfunctional.

MATERIALS AND METHODS

During an 8-month period, a total of 26 fetuses were evaluated including 14 males and 12 females with average gestational ages of 18 and 17 weeks, respec- tively. Sections of gonads and surrounding tissue were routinely prepared for histological examination and stained with hematoxylin and eosin. A search for renal elements were made in each case. Renal elements were defined as glo- meruli and tubules. In 11 cases serial sections (average of three sections) were taken when the initial section contained no renal elements. Tissue measure- ments in micrometers were determined with the aid of a 1-mm micrometer, the 40 X objective, and a reticle in a 10 X lens.

RESULTS

Glomeruli were found in juxtagonadal positions in 11 of the 26 fetuses (42 %), 6 male and 5 female, of gestational ages 11 to 21 weeks (Fig. 1). The average age of the male fetuses was 18.1 weeks and that of the females was 14.7 weeks. Of the 11 cases it was necessary to obtain serial sections in 6 before glomeruli were seen. The glomeruli and adjacent tubules, when present, were embedded in loose mesenchyme. They were located in the mesosalphinx, where one might expect to find the epoophoron, and in connective tissue adjacent to epididymis and rete testis. AU testes in this age group were, of course, intra-abdominal.

The glomeruli were cellular, measured up to 98 pm in diameter, and con- tained capillary loops whose walls were lined by cells with plump round or oval nuclei. Occasionally, a fortuitous section revealed an afferent or efferent vessel. The periglomerular capsules (the mesonephric equivalents of Bowman’s cap- sules) were lined by epithelium, which was mostly low cuboidal but partially

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FIGURE 1. Glomeruli and tubules were first noted in tissue from a 15-16-week fetus. The location (arrow) is noted in (A), which illustrates testis (T), epididymis (E), and vas deferens (V) at X 10. A mesonephric glomerulus and tubules are seen at higher magnification in (B) ( X 200). Similar structures from paraovarian tissue of an 18-19-week fetus are shown in (C) ( X 200). Note the lack of variation in tubular epithelium.

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simple squamous. One wide-mouthed opening into the proximal tubule was seen. There was immediate transition in the tubule to columnar epithelium with eosinophilic cytoplasm and brush border. The tubules as seen in cross section varied in diameter from 28 to 70 pm. The epithelium showed no signifi- cant variation in appearance.

These histological characteristics are not diagnostic of mesonephros but are consistent with it. De Martino and Zamboni (6 ) , in their histological study of embryonal mesonephros noted that each glomerulus drains into a tubule, which, in turn, drains into the mesonephric duct. They found evidence of two separate vascular poles for the afferent and efferent vessels. Lack of demonstra- tion of this phenomenon in the present study could be fortuitous, as this distinc- tion is not readily demonstrated when one is presented with a sharply limited number of glomeruli to section. Differing epithelium characteristic of proximal and distal tubules as noted by De Martino and Zamboni (6) was also not evident. Histological differentiation of mesonephric and metanephric glomeruli is difficult at best (10). Figure 2 demonstrates this lack of distinction. Candelier et al. (1 1) used six monoclonal antibodies provoked by embryonic renal cells and found nearly identical antigenic composition of mesonephros and meta- nephros.

DISCUSSION

The ease of finding juxtagonadal mesonephric glomeruli in these fetuses of 11 to 21 postmenstrual weeks indicates that their presence is not uncommon during this stage of development extending into midgestation.

The anatomical relationship between mesonephros and gonad is a close one during embryonic development. Germ cells migrate from the yolk sac to the developing gonad on the medial aspect of the urogenital ridge during the fifth and sixth postconceptional weeks (1, 12). There is evidence that stromal cells of the developing gonad are formed in part from mesonephric cells and that func- tional aspects of the gonad are influenced by the mesonephros or mesonephros- derived tissue. Grinsted and Aagesen (13) concluded that the mesonephros do- nates cells to the embryonic gonadal anlage in both sexes, secretes substances that influence the onset of meiosis in mammals, influences gonadal sex steroid production in rabbits, and influences gonadal sex differentiation in mice. Cells in the gonads that are thought to be of mesonephric origin include Sertoli cells (14, 15), Leydig cells (16), granulosa cells of the follicular wall (13), cells of the rete ovarii (1 7), and steroid-producing cells of the ovary (18).

The literature is devoid of reports of persistent fetal mesonephric glomeruli beyond the time frame in this study. There are, however, a few reports of juxtagonadal mesonephric remnants in various stages of extrauterine life. Chevassu in 1910 (19) found ectopic kidney tissue in the region of the guber-

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__ ~~

FIGURE 2. A juxtagonadal glomerulus from the same fetus as Figure 1A and B is illustrated in (A) as an example of the lack of histological distinction from a mesonephric (B) or rnetanephric ( C ) glomerulus of an embryo of 7 weeks developmental age. X 400.

naculum of the gonad of an adult. Roth and Ritter (20) reported the persistence of a ‘‘wolffian body” in the midinguinal canal of a 4-year-old whose ipsilateral testicle was at the internal ring. The tissue consisted of renal tubules and glo- meruli in mature fibrous tissue. Radiographically, the kidneys were normal. Saito et al. (21) found a mass of ectopic renal tissue adjacent to an undescended testis in a 3-year-old. It consisted of undifferentiated blastema with tubules and glomeruloid structures. The kidneys were normal by ultrasound. Goldberg and Drut (22) reported a mass at the head of the epididymis of a 7-month-old. It contained glomeruloid structures and tubules but also cells “resembling ovarian hilar cells.” The authors chose to relate this lesion to the metanephros-a vari- ant of sclerosing metanephric hamartoma.”

Extrarenal Wilms’ tumors in juxtagonadal locations or locations along the line of gonadal descent have been noted, and, at times, there is adjacent or

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intermingled benign ectopic renal tissue. Thompson et al. (23) reported Wilms’ tumors of the inguinal region in a 3-year-old boy and a 4-year-old girl. Both had normal kidneys. Akhtar et al. (24) studied a 2-month-old boy with a Wilms’ tumor loosely attached to the vas deferens in the inguinal canal. The tumor was traversed by fibrous septa containing well-differentiated tubules and glomeruli. Normal kidneys were present. The authors concluded that the tumor had arisen from preexisting mesonephric rests. Orlowski et al. (25) noted a supratesticular Wilms’ tumor in a 3-year-old boy. Adjacent tissue contained nonneoplastic tubules and glomeruli. Normal kidneys were present. It was con- cluded that the tumor arose in ectopic renal anlage of mesonephric origin.

The position of the renal tissue in cited cases (20, 25) and in the fetuses of this report, the presence of normal kidneys in normal position, histological features not inconsistent with mesonephros, and the known strong anatomical and functional associations of gonad and mesonephros lead the author to the conclusion that the observed tissues are mesonephric. Such mesonephric rem- nants are common in the gestational ages studied, but the frequency with which they persist into the third trimester and postnatal life is unknown, as is their potential for neoplastic mischief.

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Received December 1 ti, 1991 Revision accepted March 17, 1992

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