P. van der Schoot

Developmental pattern and regulation by androgens of androgen receptor expression in the urogenital tract of the rat

Distribution and regulation of androgen receptor expression during fetal and neonatal virilization of the rat fetus was assessed by immunohistochemistry. In mesonephric duct derivatives the androgen receptor expression became evident first in the efferent ductules and epididymis (on fetal day 14), subsequently in the vas deferens and finally in the seminal vesicle. Mesenchymal cells of the urogenital tubercle were positive for androgen receptors from fetal day 14 onwards. In the mesenchymal cells of the prostate anlagen, androgen receptor positive cells were found first on fetal day 16. Administration of 5alpha-dihydrotestosterone to pregnant rats from day 11 to day 20 of gestation caused a stabilization of the wolffian duct in female fetuses. The androgen receptor expression pattern became similar as found in mail fetuses, and showed an increase in density and in frequency of androgen receptor positive cells. Administration of the androgen antagonist flutamide during the same interval caused a reduction in density and frequency of androgen receptor positive cells in male fetuses. These findings indicate that androgens enhance the expression of androgen receptors in the developing rat genital tract by induction of androgen receptor positive cells, and by increasing the frequency. The developmental pattern of androgen receptor expression in the rat mesonephric duct system reflects the androgen-responsiveness of the ducts, and is consistent with induction of the androgen receptor along the ducts by testosterone reaching these structures in an exocrine fashion.

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

The term ovarian suspensory ligament appears ambiguous when human adult anatomy textbooks are compared with human embryology or with general mammalian anatomy textbooks. The term ovarian suspensory ligament in laboratory rodents and domestic animals indicates homologous structures during foetal (the cranial mesonephric and gonadal ligaments) and later life (the cranial mesonephric ligament derivatives). In human foetal anatomy textbooks ovarian suspensory ligament is generally applied to this same ligament. However, in human adult anatomy textbooks ovarian suspensory ligament is widely applied to the part of the (uterine) broad ligament which contains the uterine and ovarian blood and lymphatic vessels and nerves. This inconsistency in human anatomy books raises confusion on the nature of the foetal and adult ovarian suspensory ligaments and inconsistencies in the description of the normal anatomical relationships of the ovaries between humans and other mammals. For the proper understanding of normal gonadal growth and development within the abdomen, it is important to maintain a consistent nomenclature of the cranial ovarian structures. The current practice in veterinary and other mammalian textbooks offers a solid point of departure.

Doubts about the ‘first phase of testis descent’ in the rat as a valid concept

SummaryIt has become customary to distinguish between two stages in descent of the testis: first transabdominal migration of fetal testes from the posterior body wall to the inguinal region, and second, true descent into the developing cremaster sacs. The present study of rats examines the validity of the concept of transabdominal testis migration by histological analysis, between days 15 and 22 of fetal life, of the position of testes and ovaries relative to the site where, postnatally, the male cremaster sacs are to develop. The analysis revealed that rat testes do not migrate from the posterior body wall to the inguinal region during the last days of fetal life. It appeared that, during that period of fetal life, ovaries ascend in a cranio-lateral direction, together with the caudo-lateral poles of the kidneys, and are closely connected to them via the ovarian cranial suspensory ligaments. A similar ascent of testes seemed to be prevented by failure of cranial suspensory ligament growth. This failure may have occurred through the exposure of male fetuses to androgen, since cranial ligaments developed in male fetuses exposed to anti-androgen. The above results allow for the following conclusions. There is no evidence for active testis migration from the posterior abdomen towards the inguinal region during the latter part of rat fetal life. There is clear evidence of cranial migration of the the ovaries during the latter part of rat fetal life together with the ascending kidneys. Androgens are thought to be responsible for the failure of cranial testis ligament growth and, therefore, for failure of cranial testis migration in ovary-like fashion. For the proper understanding of the normal and disturbed process of testis descent, it seems preferable to eliminate the concept ‘first phase of testis descent’ from the description of this process, at least in the rat. Further work should reveal the interspecific generality of these conclusions.

Studies on the fetal development of the gubernaculum in cetacea.

Background. Adult cetacean males, like non‐mammalian vertebrates and other testicond mammals, have intra‐abdominal testes. There is no evidence of a processus vaginalis in them. Testicondia in cetaceans is considered secondary as they are judged, evolutionarily, the descendants of terrestrial mammals (ungulates) with testis descent. A possible argument in support of the latter contention would be that cetacean fetuses develop gubernacula which are the primordia of the processus vaginalis and other structures associated with testis descent in other placental mammals. the present study intended to analyse cetacean fetuses in this respect.

An Evaluation of the Acute Effects of Electrochemical Stimulation of Limbic Structures on Ovulation in Cyclic Female Rats

Publisher Summary This chapter deals with the effect of electrochemical stimulation (ECS) of the medial amygdala or ventral hippocampus in regular 5-day cyclic female rats. Animals in which the frontal cortex had been stimulated (FC), animals in which bilateral lesions had been placed into the medial amygdala (AME) using platinum electrodes, and animals subjected to ether anesthesia, combined with adrenocorticotropic hormone (ACTH)- or solvent-injection served as controls. Brain stimulation was performed through application of DC-current (1 mA for 20 sec) via monopolar steel electrodes. To investigate the possible role of the AME and ventral hippocampus (VH) in ovulation in normal cyclic female rats, effects of electrochemical ECS of these structures were studied during diestrus-3 (D-3) or proestrus (P). Experiments with cyclic female rats revealed that neither ECS-AME nor ECS-VH provoked ovulation after application of the stimulus at D-3 or early at P. By contrast both experimental procedures interfered with ovulation during the cycle under investigation.

Leucocyte invasion of the vaginal epithelium in the absence of bacteria in mice

Influx of leucocytes in the vagina at metoestrus occurs in germfree mice and also in sterile isotransplants of vaginal tissue in conventional mice. In contrast to the situation in rats, bacteria thus do not seem to be required for the production of postovulatory leucotactic stimuli in the vagina.

Reduction of the intake of food and water is responsible for reduction of litter growth when dams are treated with a progesterone antagonist.

Treatment of lactating rats with the anti-progestin Mifepristone or Onapristone adversely affects growth of their litters. The present studies aimed to elucidate the underlying mechanism. The treatment did not interfere with the behavioural interactions between mothers and pups, which are required for normal litter growth. Treatment with the antagonists had a stimulatory action on ovarian oestrogen production. However, ovarian hormones did not play a role in litter growth impairment, as this also occurred with lactating ovariectomized rats. Treatment with anti-progestins did not affect the concentrations of the macronutrients in milk (protein, lactose and lipid), nor did it change the fatty acid composition of lipid. Reduced litter growth was not related to a possible direct effect of exposure of the suckling young to the drugs via the milk. Direct injections into them unequivocally affected adrenal gland and testicular development, but did not affect their body-weight development. Milk secretion, as measured by the milk weight accumulating during 6 or 24 h following sudden removal of litters in advanced lactation, was not impaired by the treatments. However, the ingestion of food and water by dams treated with Mifepristone was significantly below that of control animals. It is concluded that litter growth impairment during treatment of lactating rats with anti-progestin results from the reduction of the intake of food and water by the mother.

Prolactin and delay of implantation in lactating adrenalectomized rats.

Adrenalectomy before pregnancy in rats caused the persistence of high blood levels of prolactin (PRL) throughout the ensuing postpartum lactation. The persistence of hyperprolactinaemia was without ef

A Possible Direct Effect of Prolactin on Follicular Activity

To examine whether high serum prolactin levels inhibit follicular maturation, prolactin was injected during diestrus of intact female rats or endogenous prolactin levels were raised by applying a suckling stimulus. Injections of rat prolactin (100 micrograms per injection) given 2 and 1 days before proestrus resulted in a lower estradiol production by proestrous follicles during a 4-h incubation period than follicles isolated from control rats. In 4 out of 7 animals this occurred without a change in serum progesterone and luteinizing hormone (LH) concentrations. In the 3 remaining animals corpus luteum function was activated. In these animals serum LH concentrations were decreased and follicular estradiol production was further suppressed. To study follicular development in the presence of suckling-induced hyperprolactinemia, the following experiment was performed. Removal of a 5-pup litter at Day 13 (0900 h) of lactation (Day 1 = day of parturition) resulted in ovulation at Day 16. Replacement of a new litter 24 h after litter removal did not interfere with ovulation on Day 16. This procedure allowed the study of follicular development between Days 14 and 15 in the presence of raised serum prolactin levels. It appeared that this treatment did not affect follicular growth, but in vitro estradiol production by preovulatory follicles isolated at Day 15 was lower than in follicles isolated from nonlactating animals. In 3 out of 13 animals corpus luteum function was reactivated. In these animals LH levels and follicular estradiol production were significantly suppressed. Treatment with bromocriptine (1 mg per injection) on Days 13 and 14, in addition to litter replacement, restored the high estradiol production at Day 15 without affecting serum LH concentrations. The results of this study demonstrate that in the presence of high prolactin levels, follicular estradiol production is low. The inverse relation between prolactin and follicular estradiol production in the presence of unchanged serum LH levels suggests that prolactin can have a direct action on estrogen biosynthesis of follicle cells.