Mesonephric excretory function related to its influence on differentiation of fetal gonads.код для вставкиСкачать
THE ANATOMICAL RECORD 210:551-556 (1984) Mesonephric Excretory Function Related to its influence on Differentiation of Fetal Gonads JQRGEN GRINSTED AND LO'ITE AAGESEN The Finsen Laboratory, The Finsen Institute, DK-2100Copenhagen (J.G.) and Department of Obstetrics and Gynecology, Hvidovre University Hospital, DK-2650 Huidovre (L.A.),Denmark The mammalian intermediate fetal kidney, the mesonephros, ABSTRACT is known in different species to excrete body waste products during a limited period of fetal life. Recently, the mesonephros and its derivatives have been shown to influence gonadal functions in several ways. Thus, the mesonephric cells are responsible for regulating the onset of meiosis in different mammals by the secretion of two substances, a meiosis-inducing substance (MIS) and a meiosis-preventing substance (MPS). In this paper, the relation between mesonephric kidney function and its influence on the gonads is reviewed through literature studies. It seems that cessation of mesonephric excretion precedes onset of meiosis in the ovary in different species. It is suggested that the mesonephric renal function interferes with synthesis and/or secretion of MIS or that the excreted products may interfere with the responsiveness to MIS of the germ cells. The influence of the intermediate fetal kidney, the mesonephros on the gonads, has gained much attention during the last decade. It has been shown that the mesonephros and its derivatives influence the developing gonads in the following ways (for review, see Grinsted and Fajer, 1983): 1) The mesonephros donates cells to the embryonic gonadal anlage in both sexes. 2) The mesonephros secretes substances that influence the onset of meiosis in mammals. 3) The mesonephros influences gonadal sex differentiation in mice in vitro. 4)The mesonephros influences gonadal sex steroid production in fetal and neonatal rabbit gonads. The mesonephros is known to be a fetal excretory organ in several species (a fetal kidney), a function that we have reviewed in relation to the mesonephric influence on the gonads. MESONEPHRIC INFLUENCE ON THE GONADS Point 1 Through electron microscopic evaluations, it has been shown in sheep and in mice that in the male, the mesonephric cells are inti- 0 1984 ALAN R. LISS, INC. mately connected to the developing seminiferous cords of the testis. It is thus believed that the Sertoli cells are mesonephric in origin (Zamboni et al., 1981; Upadhyay et al., 1981). In culture experiments, we have measured the amounts of sex steroids in culture media of rabbit testes grown alone and in media of testes grown with attached mesonephric tissue. These studies also indicated that the steroid-producing Leydig cells could be of mesonephric origin, since only the youngest testes, grown with the mesonephros, developed with adequate numbers of Leydig cells and with adequate steroid production in vitro (Grinsted et al., 1982). In the female mouse, the granulosa cells of the follicular wall are shown to be of mesonephric origin: in experiments with cultures of fetal ovaries with and without attached mesonephric tissue, only the ovaries cultured with the mesonephros develop follicles in culture (Byskov and Lintern-Moore, 1973; Byskov et al., 1977). Electron microscopic examinations support these experimental findings: a direct connection between the meReceived December 30, 1983; accepted July 13,1984. 552 J. GRINSTED AND L. AAGESEN TABLE I . List of tissues of different mammalian species in which MIS and MPS effect has been shown MIS Fetal mouse ovary Fetal and neonatal hamster ovary Rete ovarii of hamster before ovarian onset of meiosis Rete ovarii of hamster after ovarian onset of meiosis Follicular fluid of preovulatory human ovary Fetal mouse testis Fetal mouse rete testis and epididymis Fetal human testis Fetal human epididymis Pubertal mouse testis Pubertal mouse rete testis and epididymis Pubertal bull testis Pubertal bull rete testis and epididymis Adult human testis Adult human epididymis Adult rat testis sonephric structures and the cells forming the follicular wall has been demonstrated in mice and sheep (Zamboni et al., 1979; Upadhyay et al., 1979). An influence, however, by the surface epithelium on the gonadal development cannot be excluded, as shown by autoradiography. At the time when the basement membrane of the surface epithelium becomes discontinuous, marked cells of this epithelium are found in the gonadal stroma in fetal rats (Merchant-Larios, 1979). To what extent the cells of the developing gonads are derived from the mesonephros or the surface epithelium is not yet completely clarified. MPS References + + + Byskov and Saxen, 1976 0 and Baker, 1976 Fajer et al., 1979 Fajer et al., 1979 - Fajer et al., 1979 + - + + + + + + + + + + Yding-Andersen et al., 1981c Westergaard et al., 1984 Byskov, 1978a Byskov, 1978a Grinsted and Byskov, 1981 Grinsted and Byskov, 1981 Grinsted et al., 1979 Grinsted et al., 1979 Grinsted et al., 1979 Grinsted et al., 1979 Grinsted and Byskov, 1981 Grinsted and Byskov, 1981 Parvinen et al.. 1982 MIS is probably a substance closely related to steroids. MPS is a substance with the biochemical characteristics of a polypeptide, possessing a molecular weight of more than 5,000 daltons (Yding Andersen et al., 1981 a,b). Point 3 In cultures of differentiating embryonic mice gonads, grown with and without attached mesonephric tissue, the gonads of sexually undifferentiated male fetuses become feminized, i.e., develop into ovarianlike structures, if they are cultured in the presence of mesonephric tissue. The control group of male gonads cultured Point 2 without mesonephric tissue develop norIn culture it has been shown that the me- mally in the masculine way (Byskov and sonephros and its derivatives secrete at least Grinsted, 1981). From these experiments, we concluded that two substances in vitro: 1)A meiosis-inducing substance (MIS), able to trigger undiffer- the mesonephros influences the gonadal sex entiated fetal mouse and hamster germ cells differentiation in a feminine direction, in to enter the meiotic prophase; and 2) a vitro. meiosis-preventing substance (MPS), able to Point 4 prevent the germ cells from entering meiosis. The steroid content in the media of coculThe tissues in which activity of MIS and MPS has been shown in vitro are listed in tures from fetal rabbit gonads with attached mesonephros has been compared to the meTable 1. An indication of the presence of MIS in dia from gonads cultured alone. From these vivo has been shown histologically: within a experiments it is concluded that the male short period, germ cells of the fetal mouse and the female mesonephros influence the testis have been found in meiotic prophase steroid content differently (Grinsted, 1982). In the male, the mesonephros cannot sewhen situated outside the testicular cords, but close to the MIS-secreting, developing crete steroids but may decrease the amount of testosterone secreted by the testis cultured epididymis (Byskov, 1978b). MESONEPHROS: ONSET OF OVARIAN MEIOSIS 553 with the mesonephros. The young and prim- composition of the excretion is hypotonic, owitive sex-differentiating male gonads are de- ing to low sodium and chloride content, but pendent on the presence of the mesonephros, has a high content of urea and potassium morphologically as well as endocrinologi- (Davies and Routh, 1957). Morphological evically (Grinsted et al, 1982). dence of a n endocrine function of the mesoIn the female, the mesonephros of the fetal nephros, like the secretion of renin from the rabbit secretes sex steroids into the culture juxtaglomerular complex of the metanemedia. In addition, it is able to lower as well phros, has been found only in pig and rat as increase gonadel sex steroids in the media (Kaplan and Friedman, 1942; Sutherland and of the cocultures, at different stages. Before Hartroft, 1968), but not in man (De Martino meiosis is initiated, the steroid content is and Zamboni, 1966; Cotrutz et al., 1971; lowered by the mesonephros. After meiosis is Koga, 19721, cat or sheep (Tiedemann, 1976). initiated after birth (at day 3 postpartum) the RELATION BETWEEN MESONEPHRIC mesonephros increases estradiol content in EXCRETORY FUNCTION AND GONADAL media of the cocultures. The mesonephric inORGANIZING ACTION fluence on the ovarian steroid production is thus altered simultaneously with onset of In Table 2, cessation of mesonephric excremeiosis in the ovary (at the first day after tory capacity and regression and onset of ovarbirth). It is suggested that MIS secretion by ian meiosis are given in the species in which the mesonephric cells is associated with the these functions presently are described. mesonephric influence on the gonadal steroid The species listed in Table 2 are arranged production (Grinsted, 1982). according to the evolutionary size of their mesonephroi (Bremer, 1916; Gersh, 1937; THE MESONEPHRIC EXCRETORY FUNCTION IN Davies, 1952; Shumkina, 1960; Tiedemann, DIFFERENT SPECIES 1976). The mesonephros has been termed “the The largest mesonephroi develop in species principal excretory organ in embryonic life” in which sexual differentiation precedes the (Patten and Carlson, 19741, although it devel- onset of meiosis in the ovary (termed “species ops unevenly in different species (reviewed with delayed type of meiosis,” e.g., pig, sheep, recently in Tiedemann, 1976).In species with and rabbit [Byskov, 19791). In animals in prominent mesonephroi, numerous nephrons which the mesonephric anlage is small, the exist. Each nephron consists of a glomerulus, gonads differentiate sexually almost simula glomerular capsule, a proximal and a dis- taneously with appearance of meiotic germ tal tubule, and a collecting duct. The loop of cells in the ovary (termed “species with imHenle, which is present in the permanent mediate type of meiosis,” e.g., man, rat and kidney, the metanephros, is always absent in mouse [Byskov, 19791). the mammalian mesonephros (Tiedemann, It seems that onset of meiosis in the ovary, 1979).In species with small mesonephroi, the and thereby probably MIS secretion, is corexcretory apparatus may be underdeveloped related with cessation of mesonephric excreor completely missing (Bremer, 1916; Tiede- tory capacity and regression (Table 2). mann, 1979). Bremer (1916) has listed the No correlation could be demonstrated mesonephros according to decreasing size in through the literature between mesonephric different species as follows: pig, sheep, cat, regression and the other mesonephric influrabbit, guinea pig, man, rat and mouse. ence on the gonads. It is shown in vitro, howThe excretory function has been correlated ever, that mesonephric influence on the to the developmental stage and type of pla- gonadal steroid secretion changes, when centation (Bremer, 1916; Davies, 1952; Ham- meiotic cells appear in the ovary (Grinsted, ilton et al., 1972). In species with a more 1982). primitive type of placentation (epitheliochorIn cultures of undifferentiated fetal mouse ial or endochorial), the mesonephros is said gonads and parts of adult kidney tissue, exto possess excretory capacity, whereas in spe- tensive degeneration of the germ cells take cies with a more developed placentation type place and meiotic cells do not appear in the (hemochorial) only small and nonfunctional fetal gonads of both sexes in a n experiment mesonephroi are formed. The onset of func- (Grinsted and Byskov, not published) carried tional excretory capacity occurs when the out like the previous studies (see Grinsted mesonephric tubules differentiate into proxi- and Byskov, 1981).This observation supports mal and distal portions (Davies, 1952). The the hypothesis of a n inhibiting influence by 554 J. GRINSTED AND L. AAGESEN TABLE 2. Period of mesonephric degeneration and onset of meiosis in the ouary of different species Morphological regression Start Completed Excretory function Start Ceased Species Pig Sheep Cattle Cat Rabbit 29' 16-219,10,'1 23-26'' 35-38l 1219-211 45' 559 ? 26-40' ? 451 27'O 3310 21'-36l 1319-1620 Guinea pig Man Rat Mouse 23 2614 2514 453,435 ? ? 54-611r2 5711.12 ? 409-421 231,21,22oc19.20 First appearance of meiotic germ cells Additional literature concerning mesonephric secretion and regression 40-483.4 524 75-804.16 40-504*'7 1-2 ( P . P . ) ~ , ~ ~ 5, 9 9,13-15 9, 13 1, 14, 18 1, 9, 24, 30 3O-3Ei4x3l 5434 17- 184341 1342 2,5,35-40 11 43 Yc) ? NoneL4 None' ? ? ? 'Days post coitum or post partum (p.p.1. The species are arranged according to decreasing evolutionary size of the mesonephros. The periods in which the mesonephros possesses excretory capacity and regresses and the age at which the first meiotic germ cells are seen in the ovary are given in the table. The length of gestations are calculated in days post coitum according to Evans and Sack (19731, or Streeter (19211, if not given by the authors. The authors referred to are given below: 1. Gersh, 1937. 2. 3. 4. 5. 6. 7. 8. 9. MacCallum, 1902. Black and Erickson. 1968 Mauleon, 1969. Weber, 1897. Mihalkovics, 1885. Stanier, 1960. Sutherland and Hartroft, 1968 Tiedemann, 1976. 10. Shumkina, 1960. 11. Davies, 1952. 12. Davies and Davies, 1950. 13. Bremer, 1915. 14. Bremer, 1916. 15. Davies. 1951. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. Erickson, 1966. Winiwarter and Sainmont, 1909. Fraser, 1920. Davies and Routh, 1957 Bernier and Beaumont, 1964. Leeson and Baxter, 1957. Giannelli, 1925. Peters et al., 1965. von Kolliker, 1879. Leeson, 1957. Leeson, 1959. Leeson, 1960. Strauser, 1928. Tiedemann, 1979. 30. Tiedemann and Wettstein, 1980. kidney tissue on undifferentiated germ cells, although this particular experiment was carried out with tissues of the permanent kidney, the metanephros and not the mesonephros . Thus, it is proposed that the mesonephric kidney function or perhaps its excretory products may interfere with the onset of meiosis. The reasons for such connection can only be speculative. Whether the interference is exerted by decreased secretion of MIS or by decreased responsiveness of the germ cells to MIS is still completely unknown. ACKNOWLEDGMENTS Mrs. Inga Dybdahl is gratefully acknowledged for typing the manuscript. 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