Early development of the human mesonephros.

The mesonephrogenic cord disintegrates into approximately 35-40 provesicular cell masses which are in close contact with the mesonephric (Wolffian) duct (WD) on their lateral side. Here, the epithelium of the WD is columnar and shares a common basal lamina with the provesicular cell masses. This in turn gives rise to a sickle-shaped pseudostratified epithelium. The concavity of the sickle is filled by spherical cells, the transition of which into the surrounding connective tissue is continuous. The sickle is transformed into a distillation flask and becomes separated from the mesonephric duct while the spherical cells maintain a connection to it by a-for the time being-solid outlet pipe. The columnar epithelium of the mesonephric duct becomes a multilayered cone, whose surface is in contact with the outlet tube. Shortly after, a continuous lumen is formed in the cone and the outlet pipe which is delimited by cells becoming columnar and forming a basal lamina. The epithelial anlage of the nephron is clearly separated from the surrounding mesenchyma by these processes. The flask eventually becomes a corpusculum, the outlet pipe a secretory (proximal) as well as collecting tubule, and the cone of the mesonephric duct a mesoureter. The various sections display differentially differentiated epithelia that are clearly distinct from each other. The mesoureter behaves differently during differentiation of epi- and paragenitale: in the epigenitale, it is short and runs into the collecting tubules of the nephrons at the lateral side of the convolved tubules, whereas a long mesoureter crosses the dorsal side of the convolved tubules and joins the corresponding collecting tubules at the far end of the mesonephros in the paragenitale.

Anovular corpus luteum in a woman taking an oral contraceptive.

PIP: When laparatomy was performed on 3 women treated with a combination-type oral contraceptive (5 mg lynestrenol, 150 MCG mestranol), an anovular corpus luteum was found in 1 ovary. Dating from the start of oral therapy, the times of the operations were Day 24, Cycle 1; Day 24, Cycle 2; and Day 23, Cycle 3 (anovular corpus luteum). The anovular corpus luteum was 6.5 mm long and 3.0 mm wide and had undergone considerable regression, about 3/4 of it having been converted into an avascular hyalinized mass. An unejected ovum, contour slightly altered and size approximately equal to that of ova in ovulation-ripe Graafian follicles, was situated in the center of the hyaline mass. The unejected ovum was the first one to be observed in a completely developed corpus luteum. The membrane pellucida was wider than usual, but the nucleus, nucleolus, and corona radiata cells surrounding the ovum had undergone little change. Hormone administration may have favorably influenced conditions of metabolism within the hyaline mass. Alterations in the anovular corpus luteum were compared with those found in the second treatment cycle in a corpus luteum formed during the first treatment cycle. The anovular corpus luteum was concluded to be the regressing corpus luteum of the first treatment cycle and approximately 65 days old.^ieng

The development of the caudal ligaments of the mesonephros and of the gonads: a contribution to the development of the human gubernaculum (Hunteri).

The formation of the two caudal mesonephric folds is described. The plica uropelvina becomes the plica urogenitalis as soon as the paramesonephric (Müllerian) duct grows, and the plica inguinalis runs over the ridge of the umbilical artery to the ventral abdominal wall. Within the plica inguinalis the inguinal or caudal mesonephric ligament is formed directly subjacent to the coelomic epithelium. It interacts intensively with the mesenchyme sheath of the paramesonephric (Müllerian) duct in stage 21. It is separated by loose mesenchyme from the subjacent mesonephros and mesonephric (Wolffian) duct which therefore it does not pass beneath. In stage 23, and during the early fetal period, the caudal gonadal ligament is formed. It arises from the caudal pole of the gonads and proliferates in the space between the two genital ducts. Only the duct not destined to disappear associates with it. Therefore, in males the gubernaculum consists of the inguinal ligament of the mesonephros only. Its significance for the descent of the testis is discussed. In females the inguinal and the caudal gonadal ligaments fuse into a single strand and together form the gubernaculum.

The Mayer-Rokitansky-Küster syndrome. An analysis of its morphology and embryology. Part I: Morphology.

The histological appearance of the rudimentary uterus, endometrium, uterine tube, Gartner's duct, round ligament, vagina and ovary is described in ten case of the MRK syndrome. When the layout of the pelvic contents of patients with this syndrome is compared with that of a normal embryo of 20 mm CRL (stage 20), the following conclusions may be drawn. The MRK syndrome can be regarded as resulting from the cessation of development of the Müllerian duct, which in this condition extends only as far as its attachment to the caudal mesonephric ligament, the round ligament. The adjacent structures beyond this point, which include the connecting strand and smooth muscle bundles dorsal to the bladder and vaginal rudiment, are derivatives of the Wolffian duct or Gartner's duct respectively. Our findings suggest that this syndrome is due to a deficiency of the estrogen and gestagen receptors. This deficiency may inhibit the further development of the embryonic Müllerian duct and account for the subsequent faulty differentiation of its existing elements. It is still undecided why, in cases of the MRK syndrome, development of the Müllerian duct ceases at the attachment of the caudal mesonephric ligament (later the round ligament). Further research is necessary to answer this question.

The Mayer-Rokitansky-Küster syndrome. An analysis of its morphology and embryology. Part II: Embryology.

The Müllerian duct (MD; ductus paramesonephricus) develops independent of the coelomic epithelium above the mesonephros. This part of the duct gives rise to the infundibulum with its fimbriated ostium abdominale. The part of the duct which lies along the mesonephros as far as its caudal pole makes a contribution to the ampulla and less often the isthmus. In the area of the mesonephros the MD fuses with the Wolffian duct (WD; ductus mesonephricus). The WD gives rise to the ampulla and the isthmus. Below the caudal pole of the mesonephros, as well as beyond the attachment point of the inguinal ligament of the mesonephros, the later round ligament of the uterus, the MD develops as an outgrowth of the WD and no longer as an independent structure. The MRK syndrome is, in its formal genesis, a non-fusion of the MD with the WD. This explains the fact that in a classic case of MRK syndrome, the Fallopian tube with a very small part of the cornu uteri extends only as far as the connection with the round ligament of the uterus. Different possibilities for the origin of MRK syndrome are discussed. It is suggested that the cause of the development of MRK syndrome could be a deficiency of gestagen and/or oestrogen receptors. This would also explain the various forms of the rudimentary vagina.

[A partially duplicated vena cava inferior: clinical, macroscopic and embryologic anatomy]. / Eine partiell verdoppelte Vena cava inferior: Klinische, makroskopische und embryologische Anatomie.

Anomalies of the inferior vena cava (IVC) can become unexpected obstacles during anterior surgery exposures of the lumbar spine. Starting from a recently observed case of a partially bilateral IVC, the literature, both clinical and anatomical, was reviewed with particular respect to the requirements of spine surgery. Based on extensive radiological (especially phlebographic), surgical, and anatomical investigations, the frequency of left sided or bilateral IVC can be figured out at about 2%. The embryogenesis of the variation is contested. Our observations comprising 45 human embryos confirm the conception according to which the infrarenal segment of IVC originates from the sacrocardinal (and not from the supracardinal) vein.

Morphologic alterations in the epithelium of the human oviduct induced by a low dosis gestagen.

Morphological alterations in the epithelium of the human oviduct related to continuous administration of low dosage lynestrenol were studied in 10 women by electron microscopy. The effect of lynestrenol on the morphology of the tubal epithelium was shown to be time dependent. First the discharge of secretory products from the non-ciliated cells was inhibited. Secondary to this the synthetic activities of the cells were drastically decreased. This inactivation of the tubal epithelium reached its maximum after 6 months. At this time the epithelial cells, particularly the non-ciliated cells were almost devoid of organelles and had an electron transparent cytoplasm. In addition to the action of lynestrenol on the secretory and synthetic activities of the cells a strong ciliogenetic effect could be observed after about 3 months of lynestrenol administration. The ratio of ciliated to non-ciliated cells changed from 1:1 at the beginning of the treatment to 2.9:1 after 6 months. This ratio was then maintained and could still be found in patients who had used lynestrenol for 25 and 39 months. In contrast to the persistent effect of lynestrenol on the ciliary apparatus of the cells the synthetic activities and the secretory mechanism were partially restored with long standing use. The importance of the observed changes and their possible participation in the contraceptive action of lynestrenol are discussed.

Light and electron microscopic changes in the kidney of Wistar rats following treatment with cyclosporine A.

The morphological changes found in kidneys of patients undergoing chronic Cyclosporine A (CSA) treatment could, despite of numerous attempts, not yet be reproduced in reliable experimental models. The purpose of the present investigation was to systematically scan the in vivo fixed kidneys in CSA treated Wistar rats at the light and electron microscopic level. The study revealed changes in the proximal tubules, i.e., inclusion bodies, vacuolization, microcalcifications and regeneration. Some glomeruli displayed a thickening of the parietal sheet of Bowman's capsule. At the electron microscopic level, individual necroses of myocytes in the tunica media of afferent arterioles were observed. Thus, at the ultrastructural level, the kidneys of CSA treated normotensive Wistar rats do reveal morphological changes similar to those occurring in man.

[Contribution on the mode of action of oral ovulation inhibitors in humans. Report 2].

PIP: 5 women who had taken various ovulation inhibitors for varying duration (3-20 cycles) underwent sterilization in the 1st, 2nd, or 3rd cycle after discontinuing treatment. Urine and tissue samples were taken. Analysis showed that pregnanediol levels of the 3 women who were in the 2nd halves of their cycles corresponded to levels characteristic of a functioning corpus luteum. Tests on another group of women indicated that behavior of the ovarian function depends on length of treatment and individual reaction. Of women who had been taking pills for 1 cycle, a small group had a normal 1st cycle immediately after discontinuation; for others, ovulation was slightly early, prolonging the cycle somewhat at the expense of the proliferation phase - a true ''rebound effect.'' Long-term patients fell into 2 groups: those with longer cycles due to a slightly longer proliferation phase and those who had 1 lengthened anovulatory cycle. By the 2nd cycle, after treatment, all functions were normal again. Returning to the 5 sterilization patients, the histological examination showed functioning corpora lutea by the 2nd cycle. In 1 case, a large mature follicle, normal in all respects, was found on the 14th day of the 1 cycle. Clinical and histological results lead to the conclusion that the ovaries can normalize completely by the 2nd cycle after discontinuation of ovulation inhibitors.^ieng

[The low dosis gestagen therapy (author's transl)]. / Die Low-Dosis-Gestagen-Therapie

In young women aged 22-34 years the hormone profile under continuous therapy with 0.5 mg lynestrenol/day have been investigated. Estradiol, progesterone and FSH values have been determined in plasma by the RIA or protein-binding method, whereas LH excretion was daily measured in the urine starting on the 5th day of cycle. The low-dose-gestagen therapy shows all possible hormonal patterns ranging from the ovulatory to anovulatory one. The estradiol-17 B values in half of the patients were higher than in the cycle preceding treatment. In the first few treatment cycles all women showed markedly decreased progesterone values. However, this defect seems to recover and return to normal in later cycles. In order to be able to further explain the alterations occurring during the luteal phase under the treatment with 0.5 mg/day of lynestrenol, ovarian tissues wedge resection of women undergoing gynecological surgery has been examined macroscopically and microscopically. At the same time the hormonal profile has been determined in plasma. These investigations revealed that the morphological alterations in the ovary proceed in an unchanged way under the mentioned treatment. Histologically it could be demonstrated that ovulation is delayed by several days. The histological findings of tubal tissue (from patients who underwent sterilization) showed that the secretional activity of the tubal epithelium is considerably decreased and ciliogenesis increased. In our clinical study neither tablet nor patient failures occurred. With the exception of cycle- and tempo-disturbances no severe adverse reactions were reported. Breakthrough bleedings and spotting as well as amenorrhea in most cases manifested already in the first treatment cycles. It is important that the daily tablet is taken at midday because the maximum effect on the cervical mucus of the mini-pill therapy is most pronounced 4-6 hours after tablet intake. Especially in young patients it is recommended to get written reports on tablet intake. The strict following of these directions mainly guarantees a successful mini-pill therapy.

PIP: Hormone levels and uterine and ovarian cytology were studied in women treated with .5 mg lynestrenol/day. Plasma estradiol, progesterone, and follicle stimulating hormone were determined, and urinary luteinizing hormone excretion was measured daily starting on the 5th day of the cycle. All possible hormonal patterns, from ovulatory to anovulatory, were observed during treatment. In half of the patients estradiol-17beta levels were higher than in the cycle preceding treatment. Progesterone levels decreased markedly in the 1st few treatment cycles, but then returned to normal in later cycles. Ovarian morphology was not altered by treatment, but ovulation was delayed by several days. It is recommended that the ''minipill'' be taken at midday, since its effect on cervical mucus is most pronounced 4-6 hours later.