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Regression of subcutaneous lymphoma following removal of an ovarian granulosatheca cell tumor in a horse.

A 9-year-old Arabian mare was admitted for evaluation of multiple subcutaneous nodules and infertility. Fine-needle aspiration of one of the subcutaneous nodules resulted in a cytologic diagnosis of histiolymphocytic lymphoma. Palpation per rectum and transrectal ultrasonography revealed a mass associated with the left ovary. Excision of the ovarian tumor was performed, and a histopathologic diagnosis of granulosa-theca cell tumor was made. After removal of the granulosa-theca cell tumor, subcutaneous nodules regressed. The referring veterinarian reported that the nodules had also disappeared and then recurred after administration of a synthetic progestin. To further characterize the lymphoma and investigate this possible hormonal relationship, immunophenotyping and estrogen and progesterone receptor assays were performed. The subcutaneous lymphoma was classified as a T-cell rich B-cell lymphoma, results of estrogen receptor assays were negative, and results of progesterone receptor assays were positive. Clinical observations of subcutaneous lymphoma in horses indicate that the waxing and waning nature of these tumors may be associated with the estrous cycle, pregnancy, foaling, and lactation. Clinical observations and identification of progesterone receptors suggest that a relationship between serum steroid hormone concentrations, such as estrogen and progesterone, and subcutaneous lymphoma may exists.

Animals↗

Immunolocalization of steroidogenic enzymes P450scc, 3betaHSD, and P450c17 in the ovaries of wild raccoon dogs (Nyctereutes procyonoides).

We investigated the distribution of 3 types of steroidogenic enzymes, P450scc, 3betaHSD, and P450c17, in wild raccoon dog ovaries by immunohistochemistry. Six pairs of ovaries were obtained from wild raccoon dogs between 2001 and 2003, with 3 of the 6 pairs of ovaries containing corpora lutea. P450scc, 3betaHSD, and P450c17 were localized in the granulosa and theca cells of these raccoon dogs. Furthermore, lutein cells were stained positively for P450scc and 3betaHSD in the pregnant and non-pregnant raccoon dogs. These results suggest that granulosa and theca cells may synthesize progesterone and androgens, which may play an important role in follicular development, and that lutein cells are a major source of progesterone in wild raccoon dogs.

3-Hydroxysteroid Dehydrogenases↗

Insulin: does it induce follicular arrest in the rat ovary?

The goal of this study was to investigate histological changes of the rat ovary treated with either insulin or insulin plus human chorionic gonadotropin (hCG). The study was conducted in Celal Bayar University, School of Medicine, Animal Research Laboratory. Eighteen adult female Wistar rats were divided into three groups to receive saline, or insulin, or insulin plus hCG for 4 weeks. At the end of treatment the rats were sacrificed and the ovaries were evaluated with hematoxylin and eosin. There was no abnormal change in rats treated with saline. A thickened capsule, stromal hypertrophy and stromal cell hyperplasia, and no developing follicles, were observed in the insulin-only group. A thin capsule, developing follicles and corpora lutea, and normal theca cells and stroma were observed in the insulin-plus-hCG group. We conclude that insulin may lead to histological changes similar to stromal hyperthecosis and polycystic ovary syndrome, and may be one of the factors causing follicular arrest.

Animals↗

An update on the roles of inhibin, activin, and follistatin as local regulators of folliculogenesis.

The local actions of the inhibin-related peptides inhibin, activin, and follistatin in folliculogenesis, luteinization and atresia are reviewed. On the basis of in vitro data, it is concluded that (a) inhibin has a paracrine action positively regulating LH-induced androgen production by theca cells in addition to a peripheral role regulating FSH secretion; (b) activin has a negative paracrine action on LH-induced androgen production by theca cells; (c) activin, either alone or with FSH, has an autocrine action on granulosa cells, promoting differentiation during the preantral and early antral stages of folliculogenesis and preventing premature luteinization in the later stages of antral follicle development, leading overall to promotion and maintenance of the folliculogenic state of the follicle; and (d) follistatin modulates granulosa cell function in favor of luteinization or atresia, and its mechanism of action involves neutralizing the actions of activin by its binding properties and by a direct action of follistatin on progesterone metabolism by granulosa cells. A hypothesis for a role of activin in the acquisition of responsiveness of granulosa cells of preantral follicles to FSH is proposed.

Activins↗

Induction of maturation in follicle-enclosed oocytes: the response to gonadotropins at different stages of follicular development.

Antral follicles, isolated from either nontreated or pregnant mare's serum gonadotropin (PMSG)-primed 27-day-old rats, were incubated in the absence or the presence of either luteinizing hormone (LH), follicle-stimulating hormone (FSH), or forskolin. The effect of these agents on oocyte maturation and cyclic adenosine 3',5'-monophosphate (cAMP) accumulation was studied and compared. Both gonadotropins, LH and FSH, as well as forskolin, effectively induced maturation of oocytes enclosed by large antral follicles isolated from PMSG-primed rats. On the other hand, we found that maturation of oocytes enclosed by small antral follicles, isolated from nonprimed and PMSG-primed rats, could be induced by either FSH or forskolin but not by LH. cAMP determinations revealed that, in spite of the inability of LH to induce oocyte maturation, elevated concentrations of the nucleotide were detectable in small antral follicles exposed to this gonadotropin. Since granulosa cells isolated from the large but not the small antral follicles were stimulated by LH to generate cAMP, the elevation of cAMP concentrations in the small antral follicle apparently represented the response of the theca cells to this gonadotropin. Since it is the ability of the granulosa cells to interact with the hormone that determines whether or not oocyte maturation will occur, we suggest that the granulosa, but not the theca cells, mediate LH action to induce oocyte maturation.

Adenylyl Cyclases↗

Localization of bFGF mRNA in cyclic rat ovary, diethylstilbesterol primed rat ovary, and cultured rat granulosa cells.

Evidence from in vitro studies strongly implicates basic fibroblast growth factor (bFGF) as a local regulator of ovarian function. However, the in vivo function of this growth factor in the ovary is uncertain. The objective of this study has thus been to investigate the biological role of bFGF in the rat ovary by monitoring bFGF gene expression using in situ hybridization in 3 systems; (1) the naturally cycling ovary, (2) ovaries of immature rats treated with diethylstilbesterol (DES), and (3) primary rat granulosa cell cultures. The rat estrus cycle can be divided into 4 stages as determined by vaginal cytology; diestrus, proestrus, estrus and metestrus. bFGF mRNA transcripts were localized to granulosa and theca cells of developing follicles during proestrus and estrus and in the corpus luteum following ovulation during metestrus. The estrogen analogue DES induced extensive in vivo folliculogenesis and high levels of bFGF mRNA in both granulosa and theca cells when compared to controls. Detectable levels of bFGF mRNA were also observed in primary granulosa cell cultures grown to high density. Employment of this in situ hybridization procedure has enabled the in vivo cellular sources of bFGF mRNA to be identified and the time course of expression during the estrus cycle to be monitored. The biological significance of this expression and the interplay between bFGF, extra- and intra-ovarian modulators are discussed.

Animals↗

[The corpus luteum].

The primary function of the corpus luteum is secretion of progesterone for maintenance of pregnancy. The development and function of the corpus luteum from residual follicular granulosa and theca cells after ovulation is induced by the midcyclic peak of LH secretion followed by further pulsatile LH release. Due to this stimulation the follicular granulosa and theca cells are converted to large and small luteinized cells with high proliferation rate. During this process Vascular-Endothelial-Growth Factor (VEGF) plays a major role as a potent stimulator of neo-angiogenesis. Formation of new blood vessels is essential to ensure supply of LDL-Cholesterol as substrate for steroidogenesis. If pregnancy does not occurs, the corpus luteum must regress to initiate another cycle. Luteal regression seems to be initiated by PGF2 alpha which is secreted from the uterus. PGF2 alpha, reduces luteal blood flow and progesterone synthesis. Furthermore it is a potent inducer of apoptosis. If pregnancy occurs, sustained secretion of progesterone and other substances like estradiol and relaxin are required to provide an appropriate uterine environment for maintenance of pregnancy. In that case the corpus luteum is further stimulated by hCG secreted by the blastocyst and the trophoblast-cells until 8/9 weeks of gestational age, when synthesis and secretion of steroids is taken over by the placenta.

Corpus Luteum↗

Immunolocalization of transforming growth factor-beta1 during follicular development and atresia in the mouse ovary.

In each estrous cycle not all follicles recruited grow to ovulate, as some degenerate through the process of atresia. Apoptosis is the mechanism underlying follicle atresia. TGF-beta1 has been implicated in the induction and promotion of apoptosis in many cell types and it is expressed in the ovary. In this study immunohistochemistry was used to localize TGF-beta1 in order to correlate the growth factor expression with morphological follicular atresia during diestrus in mice. Small and medium sized follicles had no staining for TGF-beta1 in the granulosa or theca cell layer. Weak to moderate TGF-beta1 expression was present in the theca cells of both large healthy and atretic antral follicles. Large healthy antral follicles showed weak granulosa staining but this was not observed in atretic follicles. Strong TGF-beta1 staining was present in the interstitial, corpus luteum and oocytes of all follicle stages. These results suggest that in the mouse TGF-beta1 promote follicular growth and differentiation rather than follicular atresia.

Animals↗

Insulin-like growth factor binding proteins in ovarian follicles from women with polycystic ovarian disease: cellular source and levels in follicular fluid.

The follicular fluid (FF) of human ovaries contains insulin-like growth factor binding proteins (IGFBPs) which may regulate the bioavailability of the IGFs. Previously we showed discrete changes in IGFBP concentrations in FF which correlated with the physiological state of the follicle. The purpose of the present study was to test the hypothesis that IGFBPs in FF may be increased in polycystic ovarian disease (PCO). FF was aspirated from PCO follicles and size matched healthy and atretic follicles from normal ovaries of naturally cycling women. The IGFBPs in FF samples were studied by ligand blot analysis with 125I-IGF-II and by immunoblot analysis using specific antisera to five human IGFBPs. Of six IGFBP bands in PCO FF, three were identified as IGFBP-2, IGFBP-3, and IGFBP-4. Bands (29K and 31K) were not identified by any of the five IGFBP antisera. The total IGF binding capacity was increased in PCO FF relative to normal healthy or atretic FF. IGFBP-3 was the predominant BP present in FF from PCO follicles as well as normal healthy and atretic follicles with no significant difference in any of the groups of follicles studied. IGFBP-2, IGFBP-4, and the 29K BP were present in smaller amounts, but there were significantly higher levels of each of these BPs in PCO follicles than in normal healthy follicles. Only IGFBP-4 was elevated in PCO follicles relative to normal atretic follicles indicating that the pattern of IGFBP expression in PCO FF was very similar to the pattern observed in atretic follicles. To determine the source of the IGFBPs in FF, granulosa or theca cells were cultured (up to 6 days) in serum-free medium. Ligand blot analysis of the conditioned medium revealed basal secretion of IGFBP-3 by both theca and granulosa cells. FSH inhibited granulosa cell IGFBP-3 production but increased the 29K BP in the medium. Transforming growth factor-beta stimulated basal IGFBP-3 secretion and reversed the FSH effects. Human CG (100 ng/mL) inhibited theca cell IGFBP-3 production but did not stimulate any other IGFBP. The results of our studies indicate that IGFBP-2, IGFBP-4, and the 29K BP are significantly increased in PCO FF and that gonadotropins and TGF-beta regulate the production of IGFBPs by human theca and granulosa cells.

Adult↗

Distribution of the adrenocortical inner zone antigen.

Previous studies using a mouse monoclonal antibody (IZAb) have identified inner zone-specific antigens (IZAg 1 and 2) in the rat adrenal cortex. The expression of IZAg1 is enhanced by dibutyryl-cyclic AMP or ACTH in vitro and by in vivo ACTH treatment. These studies also suggest that IZAg may be involved in steriogenesis in rat adrenals. Using sensitive detection methods, the distribution of IZAg in adrenals from other species and in other rat tissues was studied. Pig and rabbit adrenals expressed an IZAb-immunoreactive protein with molecular mass identical with that of IZAg1, but no immunoreactivity was detected in bovine, guinea-pig or mouse adrenals. In the rabbit adrenal, as in the rat, IZAb bound only to zonae fasciculata/reticularis cells. However, the whole adrenal cortex in the pig immunoreacted with IZAb. Although immunofluorescence was observed in human adrenal sections, predominantly in the zona reticularis, no significant immunoreactive protein band was detected by immunoblot analysis. Apart from the zonae fasciculata/reticularis in the adrenal gland, an IZAb-immunoreactive protein with a molecular mass of 26,000 Da, corresponding to IZAg1, was also found in rat hepatocytes, renal tubules, ovary (corpus luteum, interstitial cells, theca interna of mature follicles) and Leydig cells. The observations suggest that IZAg may be involved in the processes of biosynthesis, metabolism and/or excretion of steroid hormones.

Adrenal Cortex↗

Gonadotropin stimuli increase adrenodoxin immunoreactivity in the mitochondria of rat ovarian cells.

Adrenodoxin is a component of the electron transfer system for mitochondrial cytochrome P450 in steroidogenic cells. To elucidate whether the steroidogenic state can modulate the amount and the distribution of adrenodoxin in the mitochondria, we determined immunohistochemically the distribution of adrenodoxin and 3beta-hydroxysteroid dehydrogenase (3betaHSD) in ovaries of rats under hypo- and hyperfunctional states. In the ovaries of control rats, adrenodoxin was distributed in the cristae of round-shaped mitochondria of both interstitial and theca cells. In hypophysectomized rats, no adrenodoxin was found in the mitochondria of atrophied cells. Treatment of hypophysectomized rats with human chorionic gonadotropin (hCG) or Humegon restored immunostaining of adrenodoxin in the interstitial and theca cells, and rendered the vesicular cristae of C- or ring-shaped mitochondria surrounding the lipid droplets adrenodoxin-positive. The distribution of 3betaHSD activity detected by enzyme histochemistry in these ovaries matched well that of adrenodoxin immunostaining. Our results indicate that immunostaining intensity of adrenodoxin in the mitochondria reflects the steroidogenic state in rat ovarian cells.

3-Hydroxysteroid Dehydrogenases↗

Delayed expression of the insulin-like growth factor I (IGF-I) gene in the XY sex-reversed female mouse ovary.

When the Y chromosome of Mus musculus domesticus (YDOM) mouse strain from Tirano (Italy) or Mus musculus poschiavinus (YPOS) from Poschiavo (Switzerland), is placed onto the C57BL/6J (B6) inbred background, the YDOM chromosome fails to induce normal testicular differentiation and instead allows development of ovaries and ovotestes in embryonic life. During postnatal development some hermaphroditic males become fertile whereas the XY females lack normal estrus cyclicity, produce low levels of gonadal steroids and cannot carry pregnancy to term. Here we studied the transcription of the IGF-I gene known to be involved in steroidogenesis. RNA was isolated from the XX and the XY ovaries at 1 to 40 d.p.p. and subjected to RT-PCR analysis. Immunocytochemical staining for IGF-I was performed to identify the cell type of IGF-I peptide localization, and protein expression was examined by Western blot analysis. The present results indicate that the IGF-I transcript was expressed at 1 d.p.p. in the XX ovary throughout the studied stages whereas in the XY ovary mRNA IGF-I was not detected until 15 d.p.p. IGF-I protein was identified in theca cells in the whole XX control ovary, while in the XY ovary, strong staining for IGF-I was found in the theca cells of the cortex. Faint staining was also seen around the medullary sterile cords. Western blot analysis showed normal onset in the XX and the XY ovary, but a different staining pattern for IGF-I in the XY ovary at 11 and 26 d.p.p. compared to the XX control ovary. We propose that delayed expression of IGF-I in the XY mouse ovary may be responsible for low steroid production and fertility problems in the XY sex-reversed adult female mouse.

Animals↗

Characterization of insulin-like growth factor binding proteins secreted by cultured bovine theca and granulosa cells.

Insulin-like growth factor binding proteins (IGFBPs) secreted by bovine granulosa and theca interna cells cultured in the presence of different luteinizing factors--insulin (2 micrograms/ml), forskolin (10 microM), or a combination of the two were examined and characterized. Direct binding of [125I]IGF to the conditioned media was compared to progesterone production under these different treatments. In theca cells, maximal secretion of IGFBPs was achieved using forskolin alone, whereas maximal progesterone production was induced by the insulin+forskolin treatment. In contrast, maximal secretion of both IGFBPs and progesterone in granulosa cells was achieved using forskolin alone. IGFBP species secreted by the two cell types under the different treatments were detected by ligand blotting. Conditioned media from theca cells in serum-free medium collected on the seventh day of culture exhibited three bands of 34, 40 and 44 kDa when treated with insulin or forskolin. The intensity of the 40-44 kDa complex was enhanced and a 21 kDa band appeared when cells were treated with a combination of insulin plus forskolin. Conditioned media of granulosa cells stimulated with insulin or forskolin exhibited 21, 27, 29, 34 and 40-44 kDa bands. Treatment with insulin+forskolin greatly increased the intensity of a 40-44 kDa complex. A similar shift towards high molecular weight binding proteins was observed when these media were analyzed by high-performance liquid chromatography gel filtration. These findings substantiate the secretion of IGFBPs by bovine theca and granulosa cells and show it to be dependent on culture treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Expression of messenger ribonucleic acid for the antiapoptosis gene P11 in the rat ovary: gonadotropin stimulation in granulosa cells of preovulatory follicles.

P11, a member of the S100 family of calcium-binding proteins, has been shown to interact with BAD (Bcl-xL/Bcl-2-associated death promoter) in the yeast two-hybrid protein-protein interaction assay. Because overexpression of P11 dampens the proapoptotic activity of BAD in transfected cells, we tested the possibility that the expression of this antiapoptotic protein may be regulated by gonadotropins and other survival factors in the ovary. Northern blot analysis of ovaries obtained from prepubertal rats revealed an increased expression of P11 messenger RNA (mRNA) during prepubertal development in the theca cells of preantral and early antral follicles. Treatment of immature rats with PMSG did not affect P11 expression, whereas treatment of PMSG-primed rats with an ovulatory dose of human (h)CG stimulated ovarian P11 mRNA within 6-9 h in the granulosa cells of preovulatory follicles. Treatment of cultured preovulatory follicles in vitro with LH further confirmed the time-dependent stimulation of P11 by gonadotropins. In addition, treatment of cultured preovulatory follicles with MDL-12,330A, an inhibitor of adenylate cyclase, inhibited LH-stimulated P11 mRNA, whereas treatment with forskolin, an adenylate cyclase activator, but not the protein kinase C activator, 2-O-tetradecanol-phorbal-13-acetate, mimicked the LH action, suggesting the role of adenylate cyclase activation in P11 expression. Treatment with other follicle survival factors, including the epidermal growth factor, the basic fibroblast growth factor, and interleukin-1beta, could also stimulate P11 expression in cultured preovulatory follicles. These results demonstrate the expression of P11 mRNA in theca cells of different-sized follicles and in granulosa cells of preovulatory follicles following gonadotropin stimulation, and suggest that P11 may mediate, at least partially, the survival action of gonadotropins during the ovulatory process.

Adenylyl Cyclase Inhibitors↗

Sex-dependent expression of a transcription factor, Ad4BP, regulating steroidogenic P-450 genes in the gonads during prenatal and postnatal rat development.

We investigated the expression of Ad4BP (also known as SF-1), a transcription factor regulating steroidogenic P-450 genes, in the steroidogenic tissues such as adrenal glands, testes and ovaries through the prenatal and postnatal life of rats. Ad4BP was detected in the primordial adrenal glands and gonads of the 13.5 day postcoitum (d.p.c.) fetus. After the appearance of Ad4BP, a steroidogenic P-450 (P-450(SCC)) was also detected in the adrenal glands and its amount increased gradually. In the fetal gonads of 14.5 d.p.c., a significant amount of Ad4BP was detected in the somatic cells of the testes, whereas only a trace amount was present in the ovaries. The sexually dimorphic expression of Ad4BP continued throughout the neonatal age. Drastic alterations occurred during the first to third week of postnatal age accompanied by functional and structural changes of the gonads. The expression of Ad4BP in the testes attained a maximal level one week after birth and decreased markedly thereafter. By contrast, increase of Ad4BP in the ovary was detected after the first postnatal week. Expression of P-450c17 showed a good correlation with the proliferation of Leydig cells in the testes and theca cells in the ovaries. Immunohistochemical studies revealed the presence of Ad4BP in Sertoli cells as well as Leydig cells up to the pubertal age. In the adult rat testis, however, staining of Sertoli cells decreased significantly. Ad4BP was detected in granulosa, theca, corpus luteum and interstitial gland cells in the ovary although the expression levels in granulosa cells varied among follicles. It is suggested that the Müllerian inhibitory substance gene may be a target of Ad4BP since this gene has a conserved Ad4-binding site within the promoter, which is recognized by Ad4BP expressed in the fetal testes.

Adrenal Glands↗

Cell adhesion and apoptosis in ovarian stromal hyperplasia and hyperthecosis.

The aim of our study was to investigate cell adhesion and apoptosis in ovarian stromal hyperplasia and hyperthecosis in reproductive women with and without polycystic ovarian disease. We have studied 104 patients with a histological diagnosis of ovarian stromal hyperthecosis and stromal hyperplasia. Paraffin sections were stained by hematoxylin-eosin, von Gieson and immunohistochemistry for Bcl-2 (anti-apoptotic protein) and E-cadherin (cell adhesion marker). We assessed the number of Bcl-2-positive and E-cadherin-positive cells. The patients were divided into 4 groups: group 1-33 patients with polycystic ovarian disease and coexistent stromal hyperthecosis, group 2-28 patients with polycystic ovarian disease and coexistent stromal hyperplasia, group 3-24 patients with ovarian stromal hyperthecosis, group 4-19 patients with ovarian stromal hyperplasia. Our results suggest that in ovarian stromal hyperthecosis and stromal hyperplasia coexistent with polycystic ovarian disease, E-cadherin-positivity in internal and external theca cells, and granulosa cells is associated with Bcl-2 expression. Therefore, ovarian cells expressing Bcl-2 and maintaining E-cadherin-positivity may be the viable cells that escape the apoptotic process. In ovarian stromal hyperthecosis without polycystic ovarian disease, luteinized stromal cells are potentially resistant to apoptosis as they are positive for Bcl-2. In ovarian stromal hyperplasia without polycystic ovarian disease, hyperplastic stromal cells are potentially susceptible to apoptosis as they are negative for Bcl-2. E-cadherin is negative both in stromal hyperthecosis and hyperplasia suggesting that E-cadherin expression in ovary is limited to granulosa and theca cells only. Described characteristics of cell adhesion and apoptosis may play a role in pathogenesis of ovarian stromal hyperthecosis and stromal hyperplasia with and without polycystic ovarian disease.

Antibodies, Monoclonal↗

Expression of adult T-cell leukaemia-derived factor, a human thioredoxin homologue, in the human ovary throughout the menstrual cycle.

An immunohistochemical study of the expression of adult T-cell leukaemia-derived factor (ADF), a human thioredoxin homologue, was performed in the normal human ovary throughout the menstrual cycle. Primordial follicles were negative for ADF. Both granulosa cells and theca interna cells at the stages of preantral and antral follicles contained ADF. The staining intensity of these cells was very strong in the preovulatory dominant follicle. After ovulation, both granulo-lutein and theca-lutein cells were positive for ADF. During pregnancy, the theca-lutein cells revealed very intense ADF staining. The theca interna cells of the atretic follicles showed ADF staining, while the granulosa cells of such follicles did not. These results suggest that ADF localizes in the ovarian steroidogenic cells which have the binding sites of either luteinizing hormone or follicle-stimulating hormone, and that ADF expression is closely associated with the activity of the ovarian steroidogenic cells.

Adult↗

Transplantation of reproductive organs.

A historical review of the literature concerning replantation and transplantation of reproductive organs has included studies from this laboratory, using rats, over the past 25 years. From the basic observation of ischemic and traumatic injury due to the transplantation, syngeneic testicle transplants, resulting in a partner's impregnation and histological restoration of the testicles, led to human testicular transplantation. As to the ovarian transplants, granulosa-theca cell tumors may transform into malignancies if followed for a prolonged period as intrasplenic ovaries, and high doses (15 to 20 mg/kg b.w.) of azathioprine can produce such malignant tumors in a shorter period. By caval-portal shunt, ovarian hormones enter directly into the portal blood stream and no typical granulosa-theca cell tumors were produced, owing to the fact that the liver cannot degrade all the hormones secreted by both ovaries. While en-bloc vagino-utero-ovarian transplantation in the rat is possible, no impregnation has been yet achieved. Finally, it is hypothesized that those who have acquired microsurgical techniques and have a full understanding of the anatomy of the reproductive system will not only be able to perform replantation of the penis, but also will be capable of allogeneic transplantation of genital organs, whether ethically approved or not, and sooner than one may think. In such cases a penile part may be obtained at a sex-change surgery or from a cadaveric donor, similar to other vital organ transplantation practices.

Animals↗