The Development of the Corpus Luteum: a Review

THE DEVELOPMENT OP THE CORPUS LUTEUM. 189

The Development of the Corpus Luteum: a Review.

By Francis H. A. Marshall, ITI.A., D.Sc, Carnegie Fellow, University of Edinburgh. (From the Physiological Laboratory of the University of Edinburgh.)

THE present paper is the result of an attempt to collect together and give an account of the literature of the formation of the corpus luteuni, during the last ten years, that is, since the publication of Sobotta's first paper on the corpus luteum of the mouse. Of the three original hypotheses pub forward to explain the mode of formation of the corpus luteum, and the origin of the lutein cells, that of Paterson, who regarded the structure as derived from the blood coagulum left in the cavity of the Graafian follicle after its discharge, gained few or no ad- herents among subsequent investigators. The other two theories, those of von Baer and Bischoff, on the other hand, have each received a considerable amount of support. Von Baer supposed the corpus luteum to be a connective-tissue structure, in the formation of which the membrana granulosa or follicular epithelium had no share; while Bischoff con- cluded that the lutein cells were formed by the hypertrophy of the epithelial cells of the undischarged follicle. Among the principal supporters of von Baer's view appear the names of Leuckart, His, Kolliker, Slavjansky, Gegenbaur, Benckiser, Schottlander, and Minot. Those who have adopted the alternative theory of Bischoff include Pfliiger, Waldeyer, Call and Exner, Beigel, and Schulin. 190 FBANOIS H. A. MARSHALL. The first really systematic effort to deal with the question was made by Sobotta, whose eai-liest paper on the subject was published in the ' Anatomischer Auzeiger' in 1895. In the following year the complete paper was issued. These papers describe an investigation on the development of the corpus luteum in the mouse, in which a large series of stages was examined, each of them being collected according to a definite plan, the animals being killed at known intervals after the occurrence of coition, in reference to which the period of ovulation had been previously determined. Sobotta's investigation resulted in confirming Bischoff's view that the lntein cells are the much hypertrophied epithelial cells of the undischarged follicle, the connective-tissue element which forms an anastomosis among the lutein cells being derived from the inner layer of the theca. The theca esterna is described as taking no share in the ingrowth, while the theca interna is stated to become entirely used up in the formation of the interepithelial network. The hypertrophy of the epithelial cells is described as being of the nature of a simple enlargement, unaccompanied by cell division. The cavity of the follicle is said to become eventually filled up by a central plug of connective tissue. The conclusions reached by Sobotta regarding the formation of the corpus luteum were subsequently corroborated by him in an investigation on the corpus luteum of the rabbit, the stages of development being also obtained by killing the animals at stated intervals after coition. In 1898 Stratz published descriptions of stages in. the formation of the corpus luteum of Tarsius, Tupaia, and So rex; and these agree in all essential particulars with the accounts given by Sobotta. The development of the rabbit's corpus luteum was also studied by Honore, who adopted the same method as that employed by Sobotta. According to Honore the interepithelial proliferation of connective tissue is derived in part from the theca externa, and not exclusively from the inner theca, as supposed by Sobotta; while the theca interna is THE DEVELOPMENT OF THE CORPUS LUTEUM. . 191

stated to be not entirely exhausted by the ingrowth, some .part remaining to form a layer within the outer theca, after the.full formation of the corpus luteum. Kreis's observations on the young human corpus Inteum likewise support the hypothesis put forward by Bischoff. .Belloy, who investigated the formation of the corpus luteum in the rat and guinea-pig, while regarding the lutein cells as • being derived from the follicular epithelium, describes an active proliferation of these cells soon after the follicle's rupture. No figures are given by Belloy, and it seems possible that he has confused the ingrowing cells of connective tissue from the theca interna with the membrana granulosa cells. Bouin, who also investigated the corpus luteum of the ra.t and guinea-pig, reached conclusions similar to those of Belloy. Heape, without entei'ing into a discussion on the origin of the lutein cells, lays some stress on the absence of diyision among these cells in the ovaries of certain monkeys, pointing -out that the enlargement is the result of a simple hypertrophy. Babl, writing especially on the human corpus luteum, con- cludes that the lutein cells have a double origin, arising both from the membrana granulosa and from the theca interna. A number of investigators, on the other hand, since the publication o£ Sobotta's work, have adopted the theory oi'iginally put forward by von Baer, that the lutein cells arise from the connective-tissue wall, the follicular epithelium being either completely discharged along with the ovum and the greater part of the liquor folliculi, or else being partially discharged and partially degenerating in situ. Among those holding this view are His, Kolliker, and Paladino, who have lately reiterated their former opinions. Von Baer's theory has also received considerable support in recent years from Nagel, who has described the corpus luteum in the human subject as an entirely connective-tissue structure. In this he has been followed by Clark, who worked .on the formation of the corpus luteum in the sow. and in .the 192 FJUNG1S H. A. MARSHALL. human female, and claimed that the result of his investigation had put the matter almost beyond question. Clark's account has been confirmed by Doering, who also worked upon the sow's corpus luteum. Others who have adopted the view that the luteiu cells have a connective-tissue origin are Biihler, Wendeler, and Stockel, who have examined and described developing human corpora lutea. None of these investigators, however, appear to liave given an account of the growing corpus luteum in all stages of development, while in the case of several of the accounts, it is not clear that the structures described were not in reality atretic follicles, that is to say, follicles which had undergone degenerative changes without discharging their ova. On the other hand, the words used in a description by Clark point to the conclusion that this author was dealing with the degenerate epithelial cells of an atretic follicle. It seems not improbable that the young human " corpus luteum" which Doering describes was also an undischarged atretic follicle; while Kolliker's opinion that the corpus luteum is a connective- tissue structure appears to he founded on the assumption that the changes undergone by discharged follicles and retrogressive undischarged or atretic follicles are identical in character. His, and also Biihler, with reference especially to Sobotta's work on the mouse, have remarked that it can scarcely be au accidental circumstance that the accounts given of the development of the corpus luteum in the larger animals and in man are radically different from those described for the smaller species. That the discrepancy between the accounts of various investigators depends upon the size of the animals employed does not seem, on the face of it, a very probable suggestion. It is to be noted further that in the investigations of all these writers who have upheld the connective-tissue theory the ages of the developing corpora lutea were unknown, the material in no case being obtained by Sobotta's method of killing the animals at definite intervals after coition. In 1901 the present writer published a preliminary account THE DEVELOPMENT OF THE CORPOS LUTEUM. 193 of an experimental inquiry upon the formation of the corpus luteum in the sheep. In this inquiry the sheep were killed at stated periods either after coition or after the animals had been observed to undergo oestrus. The relation which was found to exist between the condition of development of the corpus luteum and the leDgth of the interval that was allowed to elapse between cestrus and the killing of the animalj was in itself a strong presumption that ovulation in the sheep occurs normally during oestrus. Thus the approximate age of the young corpus luteum or discharged follicle could in every case be determined. The result of this investigation was to confirm in all essential particulars Bischofi's theory, which had been accepted by Sobotta. The sheep, however, was found to present some differences from the mouse in regard to the mode of formation of the corpus luteum, the connective tissue ingrowth beingderived partly from the theca externa, and not merely from the theca interna, and the follicular epithelium continuing to undergo division after the rupture of the follicle, but with greatly decreased frequency. The former of these two observations is in agreement with Honore's statement in regard to the interepithelial connective tissue in the rabbit. The theca interna was said to become entirely used up in the formation of the connective-tissue ingrowth, this statement agreeing with Sobotta's description, but differing from that of Honore. Two years later the complete account of the development of the corpus luteum in the sheep was published. The description given in these papers is thus completely opposed to His's suggestion that the mode of formation of the corpus luteum in the larger mammals is different from what it is in small animals like the mouse and rabbit, unless, as Sobotta remarks, it was intended to include only the ele- phant and the whale in the former category. Meanwhile, in 1901, the same year in which the preliminary account referred to above was issued, van der Stricht published descriptions of the developing corpus luteum of bats belonging to the genera Vesperugo, Vespertilio, and Placotus. This author's researches also resulted in eon- 194 FRANCIS H. A. MARSHALL. firming Bischoff's hypothesis, but he differs from others who hold this view in stating that a certain relatively small number of lutein cells arise from interstitial cells existing in the inner theca of the connective-tissue sheath. Van der Stricht differs from Sobotta, while agreeing with the preseut writer in finding mitotic division among the follicular epithelial cells after the follicle's rupture. A figure is given iu one of van der Stricht's papers of a section of a human ovary in which such division is also shown to exist. It would thus appear that the lutein cells, at any rate, in.certain mammals, do not arise entirely by simple hypertrophy of the follicular epithelial cells, but by hypertrophy accompanied by a greater or less amount of cell division. The very early appearance of fatty particles in these cells in the bat's discharged follicle is a point of considerable interest to which van der Stricht calls attention. At the meeting of the " Anatomische Geselischaft" at Bonn, Kopsch exhibited sections of corpora lutea from the sow, representing three-, six-, and ten-day stages of development. These preparations in a general way supported the follicular epithelial theory.1 Sobotta's account of the formation of the corpus luteum in the rabbit has been recently further confirmed by Cohn, who also obtained a series of stages by killing the rabbits at stated periods after copulation. Thus the development of the rabbit's corpus luteum has formed the subject of experimental investigations by three separate observers—Sobotta, Honore, and Cohn,—who have all arrived at the conclusion that the lutein cells are hypertrophied follicular epithelial cells. An important paper on the corpus luteum of the " Marsupial cat," Dasyurus viverrinns, by Sandes shows that this structure is formed in a similar way in marsupials to what it is in the Eutheria. The theca interna folliculi is shown to be rudimentary in Dasyurus. Owing to this circumstance Sandes points out that it is easier to follow the subsequent changes 1 Vide Sobotta, Merkel and Bonnet's 'Ergebnisse d. Anat. u. Entwick.,' vol. xi, 1902. THE DEVELOPMENT OF THE CORPUS LUTEUM. 195 undergone by this layer dui'ing the formation of the corpus luteum than in certain of the other mammals. Biihler had susrafested that Sobotta might have confused the cells of the theca interna during an early stage of ingrowth with those belonging to the follicular epithelium, which they undoubt- edly at one period resemble, saying that the latter author had not properly described the connective tissue sprouting into the cavity of the newly-discharged follicle. Sandes's •description is of value as showing that Biihler's criticism loses all force when applied to Dasyurus, with which the membrana granulosa undergoes so considerable a hypertrophy prior to the thecal ingrowth as to sometimes almost fill the cavity of the follicle, and thus all possibility of a confusion between epithelial and connective-tissue cells is precluded. Sandes describes also the fate of those follicles which do not rupture in Dasyurus. In the case of the smaller follicles both follicular epithelium and ovum frequently degenerate, but the former may persist as a single layer of cuboidal epithelium. Sometimes a metaplasia of epithelial cells into spindle- or star-shaped cells is said to take place, as in other animals. In this way the cavity of the follicle becomes filled up, or it may be obliterated by the ingrowth of connective tissue. Other atretic follicles may for a time remain cystic, with a layer of cuboidal epithelial cells, which eventually dis- appear. Follicles which have become ripe, or almost ripe, however, are stated to pass through changes precisely similar to those undergone by corpora lutea, except that the ovum, instead of being extruded, degenerates in situ, becoming invaded by leucocytes and by connective tissue. The corpus luteum in the marmot (Spermophilus citillus) has been shown by Vb'lker to be formed in essentially the same way as that of the mouse, the rabbit, and the sheep. It resembles that of the sheep and (according to Honore's description) that of the rabbit, in the fact that the thecal iu- growth is not merely confined to strands of tissue arising from the inner layer. It also resembles the rabbit's corpus luteum (according to Honore) iu that the theca interna need 196 FRANCIS H. A. MARSHALL. not become entirely spent in the formation of the interepithelial connective tissue. Volker finds also in unruptured atretic follicles lutein cells which are similar to those of discharged follicles. Two authors who have recently written on the formation of the corpus luteum reject Bischoff's theory, on what substantial grouuds I find it difficult to understand. Of these, Jankowsky bases liis opinions on the study of a miscellaneous collection of material obtained mostly from the sow, but without any attempt at systematic investigation. The few figures which this author gives do nob seem to me in any way opposed to the follicular epithelial theory, while the figure of the developing corpus luteum from the guinea-pig appears rather to support the hypothesis that the hypei'trophied cells arise from the membrana granulosa, and the anastomosis between those cells from the tissue of the theca. Jankowsky's view is largely based on the appearance of " lutein cells " in the theca interna prior to the rupture of the follicle. Williams, in a recent work on obstetrics, takes up the same position as Jankowsky, partly on the ground that " the membrana granulosa presents extensive degenerative changes, and is usually cast off in great part at the time of rupture," and partly because the cells of the theca interna undergo marked changes during the follicle's development, and eventually come to resemble lutein cells. The former statement, indeed, is very far from being proved, while the latter appears to me to be singularly inconclusive. Williams argues also that the degenerative changes which have been observed in the epithelium of atretic follicles afford evidence that similar changes occur in discharged follicles. "Obser- vations based upon the study of several hundred human1 corpora lutea have convinced me that the connective tissue origin of the lutein cells is established beyond all reasonable doubt." Williams, however, does not say that these speci- mens have been described in any published paper, and, in the absence of the evidence, I am unable to regard his opinion as in any way conclusive. THE DEVELOPMENT OF THE CORPUS LUTEUM. 197 The changes undergone by the discharged follicle have also been studied in various lower vertebrates. J3iihler, who investigated the ovaries of Cyclostomes and certain Teleosteans, was unable to find any hypertrophy of the follicular wall, and Cunningham arrived at a similar conclusion for the spent follicles of Teleosteans. The present writer has examined the discharged follicle of the common fowl without being able to detect any hypertrophy of the follicular epithelium. On the other hand, Mingazzini has discovered such hypertrophy in certain reptiles, structures resembling mammalian corpora lutea being found to occur; while Giacoraini, who has investigated the subject in birds, amphibians, and, more particularly, in elasmobranch fishes, also gives an account of the formation of corpora lutea by the hypertrophy of the follicular epithelium. The latter author describes and figures the corpus luteum of Mylio- batis as a glandular body in which the follicular epithelium is penetrated by an extensive ingrowth of connective tissue and blood-vessels. This account agrees substantially with what is found to take place in the mouse, the rabbit, and the sheep. A similar description is given by Wallace of the spent follicles in the fishes Zoarces and Spinax. Zoarces, however, presents a comparatively slight resemblance to the mammals in regard to this point, there being merely a slight hypertrophy of the follicular epithelial cells. In Spinax> on the other hand, there is a considerable hypertrophic enlargement of these cells, together with a thecal ingrowth at various points in a radial manner, and an ingrowth of blood-vessels. LuceiD has also described corpora lutea in the reptiles Anguis and Seps, with which there is a simple hypertrophy of the cells of the follicular epithelium, unaccompanied by ruitotic division. It thus appears that the follicular epithelial theory of the origin of the corpus luteum of mammals has been found to be true also for various members of the other vertebrate groups. The chief results obtained by the investigations of Sobotta, 198 FBANCIS H.A. MARSHALL. ' Strata, Honore, van der Stricht, Colin, Sandes, Volker, and the present writer, all of whom agree in adopting this theory, may be summarised as follows : The lutein cells of the fully-developed corpus luteum represent the epithelial cells of the undischarged Graafian follicle. These cells, after rupture, undergo an enormous hypertrophy, which may be accompanied in the earlier stages by mitoti.c division, but usually only to a relatively slight extent (Ovis, Vesperugo, etc.). Meanwhile, the thickness of the wall of the developing corpus luteum is further increased by an ingrowth of connective tissue from the side of the follicle, forming eventually an anastomosis of cells, generally fusiform in shape, between the hypertrophying follicular epithelial cells. This connective tissue is derived either from the theca interna alone (Mus, Tarsius, Tupaia, Sorex, Dasyurus, Vesperugo, etc.), or it may arise from both theca interna and externa (Lepus, Ovis, Spermo- philus). The formation of the anastomosis is accompanied by an ingrowth of blood-vessels, which gradually increase in number throughout the young corpus luteum. The theca infcerna may become entirely spent in this process (Mus, Tarsius, Tupaia, Sorex, Ovis, Dasyurus), or certain strands of this layer may remain outside the hypertrophied epithelial cells after the complete formation of the corpus luteum (Lepus, Spermopliilns, Vesperugo, etc.). Cer- tain cells in this layer are stated in some cases to become trans- formed iuto lutein cells (Vesperugo, etc.). The cavity of the discharged follicle becomes completely filled in eventually by the further growth inward of connective tissue accompanied by blood-vessels. The corpus luteum may attain to very great dimensions, this structure, when fully formed, in the cow, having a diameter of from two to three centimetres, according to Schmidt.1 Its large size is all the more remarkable in view 1 Schmidt's paper, besides containing observations on the corpora lutea, lias also an interesting account of the variation noted in the duration of the cestrous cycle, or the interval between two successive "heat" periods, in THE DEVELOPMENT OF THE CORPUS LUTEUM. 199 of its resulting fco a large extent from the simple hypertrophy of certain of its constituent cells, namely, those which com- prised the epithelium of the ripe follicle. The wonderful property which these cells possess of enlarging within a very short time of the follicle's rupture, a rapidity which seems to be especially marked in the case of the sheep's corpus luteum, is apparently without parallel in the histology of the Verte- brata. This unique characteristic becomes additionally interesting when considered in relation to Pfluger's hypothesis, since supported by Schafer and others, that the cells of the follicular epithelium have a totally different origin from those belonging to the thecal tissue, being in f;ict derived from the same group of cells as that from which tlie ova arise.

POSTSCRIPT. Heape, in a recently published paper, describes the formation of the corpus luteum in the rabbit as follows:—"The corpus luteum is formed by the ingrowth of cells surround- ing the follicle together with the follicular epithelium; the ingrowth being at one time apparently a forcible rush before which the loosened epithelium is driven. The ingrowth takes place in the first instance in the region of the base of the follicle." Miss Lane-Olaypon, in a paper lately communicated to the Physiological Society, " On the Post-Natal Formation of Primordial Ova," states that the ovarian interstitial cells, and the follicular epithelial cells, like the primordial ova, are all " derived from the original ingrowths of the germinal epithe- cattle, as deduced from the study of 500 cases. The most usual length of this period appears to be twenty-one days, but the variation was found to range from six days to one hundred and twenty-one, or even more days. All variations between these periods were noted to occur. Schmidt's observations are in direct opposition to Beard's speculation regarding the " Span of Gestation and the Cause of Birth " (Jena, 1897), according to which the interval between two " heat " periods is assumed to bear a fixed relation to the length of the gestation period. VOL. 49, PART 1.—NJfiW SERIES. 15 200 FRANCIS H. A. MARSHALL.

Hum," and not " from the mesoblast, which gives rise to the connective tissue and blood-vessels." If the epithelial and interstitial cells are potentially and by origin identical, this fact helps to elucidate Van der Strieht's discovery that in the bat's ovary both of these elements may take part in the formation of the lutein cells. It is possible also that it pro- vides an explanation of some of the discrepancies between statements by various authors regarding the mode of development of the corpus luteum in different animals. Miss Lane-Claypon says that in the rabbit "the interstitial cells form by far the largest part of the adult ovary," while in the sheep, judging by my own observations, they are relatively scarce. F. H. A. M. September 28th, 1905.

LITERATURE SINCE THE YEAR 1895.

BELLOT.—" Recherohes sur l'origine des corps jaune de l'ovaire chez le rat et le coclion d'Inde," ' C. R. de l'Assoc. des Anatomistes,' premiere session, Paris, 1899. BOUIN.—" Atreae des follicules de la Graaf et la formation de faux corps jaunes," 'Bibl. Anat.,' 1S99. BiiHLER.—" Eutwickelungsstadien menschlicher Corpora lutea," 'Verliand.d. Auat. Gesellschaft in Pavia,' 1900. BUHLER. —" Ruckbildung der Eifollikel bei Wirbelthieren," 'Morphol. Jabr.,' vol. xxx, 1902. CL4.UK.—"Urspruug, Wacbstum und Ende des Corpus luteum, etc.," ' Arch. f. Anat. u. Phys., Anat. Abtli.,' 1898; American translation in 'Johns Hopkins Hospital Reports,' vol. vii, 1899. COIIN.—" Zur Histologie und Histogenesis des Corpus luteum und des inter- stitiellen Ovarialgewebes," 'Arch. f. Mikr. Anat.,' vol. Ixii, 1903. CUNNINGHAM.—" On the Histology of the Ovary and of the Ovarian Ova in certain Marine Fishes," ' Q. J. M. S.,' vol. xl, 1897. DOEBING.—"Beitrag zur Streitfrage iiber die Bildung des Corpus luteum," 'Anat. Anz.,' vol. xvi, 1899. GIACOMINI.—" Contributo all'istologia dell'ovario dei Selaci," 'Ricercave Laboratoria di Anatomia normale della Roy. Universita di Roma,' vol. v 1896. THE DEVELOPMENT OP THE COEPUS LUTBUM. 201

HEAPE.—"The Menstruation and Ovulation of Macacus rhesus,"'Phil. Trans., B,' vol. clxxxviii, 1897. HEAPE.—" Ovulation and Degeneration of Ova in the Rabbit," ' Proc. Roy. Soc, B,' vol. lxxvi, 1905. His.—Discussion,' Verli. d. Anat. Gesell.,' Tubingen, 1899. HONOMB.—"Reclierches sur l'Ovaire du Lapin. II. Reclierclies sur la For- mation du Corps Jaune," 'Archives de Biologie,' vol. xvi, 1900. JANKOTVSKY.—" Beitrag zur Entstehung des Corpus luteum der Saugetiere," 'Arch. f. Mikr. Anat.,' vol. Ixiv, 1904. KOLLIKEU.—"Ueber der Entwickelung der Graafschen Follikel," 'S. B. phys.-med. Gesell. zur Wiirzburg,' 189S. KOLLIKEK.—"Ueber Corpora Lutea Atretica bei Saugetieren," ' Verh. d. Anat. Gesell.,' Kiel, 1S98. KREIS.—"Tiber Entwickelung und lluckbildung des Corpus luteum spurium beim Menschen," ' Arch. f. Gynakol.,' vol. lviii, 1899. LANE-CLAYPON.—" On the Post-natal Formation of Primordial Ova,1'' Proc. Phys. Soc.,' 'Journ. of Phys.,' vol. xxxii, 1905. LUCIKN.— "Note preliminaire sur les premieres phases de la formation des

corps jaune chez certains reptiles," ' C. R. de Soc. de Biol.,' vol. lv3 1903. MAESTIAXL.—"Tlie (Estrous Cycle and the Formation of the Corpus Luteum in the Sheep," 'Phil. Trans.,'B, vol. exevi, 1903; "Preliminary Com- munication," 'Proc. R. S.,' vol. lxviii, 1901. MINGAZZINI.—" Corpi lutei veri e Galsi da rettili," Ricerche ve Labol. di Anat. Norm, di Roma,' vol. iii, 1893. NAGEL.—"Die weiblichen Geschlechtsorgane," article in Bardelben's ' Hand- buch der Anatomie des Menschen,' vol. vii, Jena, 1896. NAGEL.—" Tiber neure Arbeiten aiif dem Gebiete der Anatomie der weiblichen Geschlechtsorgane," Merkel and Bonnet's ' Ergebnisse d. Anat. u. Ent- wickelungs,' vol. viii, 1899. PALABINO.—"Per la dibuttata questione sulla essenza del corpo luteo," 'Anat. Anz.,'vol. xviii, 1900. RABL.—"Beilrag zur Histologie des Eierstocks, etc.," 'Anat. Hefte,' vol. xi, 1898. SANDES.—"The Corpus Luteum of Dasyurus viverrinus, etc.," 'Proc. Linn. Soc. of New South Wales,' vol. xxviii, 1903; abstract in ' Nature,5 August 20th, 1903. SCHMIDT.—"Beitrage zur Physiologie der Bruust beim Rinde," 'Trans. Dissert.,' Zurich, Miinchen, 1902. SOBOTTA.—"Tiber die Bildung des Corpus luteum bei der Maus," 'Anat. Anz.,' vol. x, 1S95. 202 FBANCIS H. A. MARSHALL.

SOBOTTA.—"Tiber die Bildung des Corpus luteum bei der Maus," ' Areb. f. Mikr. Anat.,' vol. xlvii, 1896. SOBOTTA.—"tJber die Bildung des Corpus luteum beim Kaninchen, etc.," 'Anat. Hefte,' vol. viii, 1897. SOEOTTA.—"Noch-einmal zur Frage der Bildung des Corpus luteum," 'Arcli. f. Mikr. Anat.,' vol. liii, 1898. SOBOTTA.—" Uber die Entstelmng des Corpus luteum der Saugethiere," Merkel and Bonnet's 'Ergebnisse der Anat. und Entwick.,' vols. viii and xi, 1899, 1902. SOBOTTA.—"Das Wesen die Entwicklung und die Funktion des Corpus luteum," • S. B. der phyp.-med. Gesell. zur Wiirzburg,' 1904. STOCKEL.—" Ueber die cystische Degeneration der Ovarien bei Blasenmole, etc.," ' Sep. Ausdruck aus der Festschrift fur Fritsch.' STRATZ.—'Der Gesclilechtsreife Saugethiereierstock,' Haag, 1898. STRICUT (VAN DEE).—"La ponte ovarique et l'histogenese du corps jaune," 'Bull, de l'Acad. Roy. de Medecine Belgique,' 1901. STRICHT (VAN DER).—"La rupture du follicule ovarique et l'histogenfese du corps jauue," ' C. R. de l'Assoc. des Anatomistes,' 3e session, Lyon, 1901. STBICHT (VAN DER).—"Une anomalie interessante de formation du corps jaune," Gand, 1901. STRICHT (VAN DER).—"L'atresie ovulaire et l'atresie folliculairs du follicule de Graaf, dans l'ovaire de chauve souris," ' Verhand. d. Anat. Gesell., Bonn,' 1901. VOLKEE.—"Uber die Histogenese Corporis lutei bei den Ziese! (Spermo- philus citillus)," 'Bull. Internat. Acad. Sci.' (Medicine), Prague, 1904. WALLACE.—"Observations on Ovarian Ova and Follicles in certain Teleo- stean and Elasmobranch Fishes," 'Q. J. M. S.,' vol. xlvii, 1903. WENDELER.—Martin's 'Die Krankheitcn der Eierstocke und Nebeneier- stocke.' WILLIAMS.—'Obstetrics,' New York and London, 1901.