New breeding opportunities with deep cornual insemination: exploiting modern sperm technologies in cattle.
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Animals↗
Biomedical subjects
R H Hunter
Publications and source records attributed to R H Hunter.
Histophysiology of the Fallopian tubes in relation to sperm binding, release, and completion of capacitation.
This paper is concerned with endosalpingeal specialisations that underlie stabilisation of unique secretions forming microenvironments within the Fallopian tube lumen, not least as they influence the final stages of sperm transport and maturation. In particular, a specific microenvironment at the ampullary-isthmic junction in the presence of the newly-shed oocyte(s), associated granulosa cells and their secretory products is thought to characterise the site of fertilisation. Attention is also drawn to the viscous glycoprotein in the caudal isthmus before ovulation: it isolates spermatozoa stored with suppressed motility from the metabolic stimulation caused by uterine or ampullary fluid. This viscous secretion strips male antigens from the sperm surface, facilitating their preovulatory binding reactions to organelles of the isthmus epithelium. Peri-ovulatory activation of discrete numbers of viable spermatozoa is regulated by follicular progesterone secretion, but seemingly involves local mobilisation of Ca2+ ions into bound gametes of appropriate membranous maturity. Motility and progression to the site of fertilisation may be further heightened by an influence of catecholamines diffusing from the myosalpinx; receptors for such molecules are present on the sperm surface. There is tight control of sperm activation and release close to the time of ovulation, generating initial sperm:egg ratios at the ampullar-isthmic junction of close to unity. However, with establishment of the block to polyspermy in newly activated eggs and lapse of time after ovulation, control of sperm progression soon relaxes. Indeed, 2-4 cell embryos may contain large numbers of accessory spermatozoa on or in the zona pellucida.
Animals↗
Risperidone versus typical antipsychotic medication for schizophrenia.
BACKGROUND: The 'conventional' neuroleptic drugs, such as haloperidol and chlorpromazine, are frequently used as the first line treatment for people with schizophrenia. However, about 5-25% of these people show poor response to these treatments and side effects often makes compliance with the 'older generation' of drug treatment problematic. Although the efficacy of these medications with respect to 'positive' symptoms is well described, little evidence exists that 'conventional' antipsychotic treatment has any effect on the 'negative' symptoms of schizophrenia. Risperidone is one of the 'new generation' neuroleptic compounds. As well as its reputed tendency to cause fewer movement disorders it is claimed that risperidone may improve negative symptoms. OBJECTIVES: To evaluate the effectiveness of risperidone for schizophrenia in comparison to 'conventional' neuroleptic drugs. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1980-1997), Cochrane Schizophrenia Group's Register (1997), The Cochrane Library (1997, Issue1), EMBASE (1980-1997), MEDLINE (1966-1997), PsycLIT (1974-1997), and SCISEARCH (1997) were undertaken. References of all identified studies were searched for further trial citations. Pharmaceutical companies and authors of trials were contacted. SELECTION CRITERIA: All randomised trials comparing risperidone to any 'conventional' neuroleptic treatment for those with schizophrenia or other serious mental illnesses. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were also independently extracted. Sensitivity analyses on dose of risperidone, haloperidol and duration of illness were undertaken for the primary outcomes of clinical improvement, side effects (movement disorders) and acceptability of treatment. For homogeneous dichotomous data the odds ratio (OR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. MAIN RESULTS: Twelve short-term studies and two long term studies provided data on 3401 people. This review provides no evidence relating to the effect of risperidone on cognitive or social functioning, quality of life, employment status, discharge from hospital and relapse rates. Risperidone increases the odds of moderate clinical improvement (OR 0.65, CI 0.55-0.77, NNT 10, CI 7-16). It appears to have little or no additional effect on the positive and negative symptoms of schizophrenia but did have less tendency to cause movement disorders, largely in comparison with haloperidol (OR 0.43, CI 0.34-0.55, NNT 7, CI 5-10) for use of antiparkinsonian medication. Risperidone seems to be more acceptable to those with schizophrenia (OR 0.69 CI 0.57-0.83, NNT 15, CI 10-30, 30% baseline risk of dropping out). Those taking risperidone are also marginally less likely to experience somnolence (OR 0.78, CI 0. 61-0.99, NNT 22). Weight gain, however, is more likely with risperidone (OR 1.51 CI 1.14-2.00, NNT 13). Funnel plots show that smaller studies generally show greater benefit for risperidone than larger studies. A publication bias in favour of risperidone amongst the included studies may explain this effect. Sensitivity analyses on dose of risperidone (excluding those receiving 1 or 2 mg) did not materially change the results for the principal outcomes. Excluding data from those on higher doses of haloperidol (>10mg/day) does marginally change the results. Risperidone is less effective in achieving clinical improvement and preventing dropout but outcomes relating to movement disorders change little. REVIEWER'S CONCLUSIONS: Little can be concluded about the long term effects of risperidone and generalising results beyond a comparison with haloperidol would be imprudent. Risperidone may be more acceptable to those with schizophrenia and have marginal benefits in terms of limited clinical improvement and side
Antipsychotic Agents↗
Treatment, management, and control: improving outcomes through more treatment and less control.
Outcomes in psychiatric care are improved by expanding treatment options and reducing dependence on management and control interventions.
Adult↗
Pre-ovulatory graafian follicles are cooler than neighbouring stroma in pig ovaries.
Using an infra-red camera, domestic pig ovaries were thermo-imaged almost instantaneously at laparotomy or within a closed abdomen by endoscopy. Rectal and jugular vein temperatures were recorded using thermo-probes. Graafian follicles (7-10 mm diameter) were cooler than ovarian stroma in all experimental models examined, and both compartments were cooler than rectal and jugular temperatures. The mean difference between follicles and stroma in 73 observations was 1.3 +/- 0.1 degrees C. When thermo-imaged under the fimbriated extremity of the Fallopian tube, follicles and stroma could still be distinguished. Follicles cooled slightly more rapidly than adjoining stroma during the first 10 s of a 60 s recording interval, after which curves for the two tissues remained parallel. Arresting ovarian blood supply for 5 min had a negligible influence on the temperature differentials. Endoscopy in three models recorded mean differentials between follicles and stroma of 0.6 +/- 0.1 degrees C to 1.1 +/- 0.1 degrees C. It is concluded that temperature gradients do exist in the ovarian tissues of mature animals, and that these are generated at least in part as a consequence of endothermic reactions within Graafian follicles.
Animals↗
Hysteroscopic insemination of small numbers of spermatozoa at the uterotubal junction of preovulatory mares.
Mares were inseminated with motile spermatozoa suspended in 30-150 microliters Tyrode's medium directly onto the uterotubal papilla at the anterior tip of the uterine horn, ipsilateral to the ovary containing a dominant preovulatory follicle of > or = 35 mm in diameter, by means of a fine gamete intrafallopian transfer (GIFT) catheter passed through the working channel of a strobed light videoendoscope. Insemination of 10, 8, 25, 14, 11 and 10 mares with, respectively, 10.0, 5.0, 1.0, 0.5, 0.1 or 0.001 x 10(6) motile spermatozoa resulted in conception rates of, respectively, 60, 75, 64, 29, 22 and 10%. Deposition of 1.0 x 10(6) motile spermatozoa onto the uterotubal papilla began to approach the limit of successful fertilization. These doses are far lower than the 3-15 x 10(9) spermatozoa normally ejaculated by fertile stallions during mating, and the accepted minimum dose of 500 x 10(6) spermatozoa used for conventional uterine body insemination in mares. The simplicity of the technique offers a practical means of exploiting new breeding technologies that require very small numbers of spermatozoa in horse breeding.
Animals↗
Ovarian follicular fluid, progesterone and Ca2+ ion influences on sperm release from the fallopian tube reservoir.
As a means of determining whether ovarian follicular fluid reaches the functional sperm reservoir in the caudal isthmus of the Fallopian tube shortly after ovulation, 0.01-0.02 ml aliquots of whole or steroid-free follicular fluid were introduced into the distal extremity of the isthmus within 1 hr before ovulation. Eggs were recovered during a second intervention 4 hr 45 min-6 hr 10 min after treatment and examined by phase-contrast microscopy for the normality of fertilisation. In a separate experiment, 0.01-0.02 ml aliquots of 10 microM calcium ionophore solution were introduced into the same site in comparable animals. Sixty-nine fertilised eggs were recovered from 12 fallopian tubes treated with whole follicular fluid, of which 24 (34.8%) were polyspermic. The 12 contralateral control tubes (PBS-treated) yielded 47 fertilised eggs, of which only one (2.1%) was polyspermic (P < 0.001). Steroid-free aliquots of the same follicular fluid introduced bilaterally into eight fallopian tubes (4 animals) resulted in recovery of 59 fertilised eggs, of which only one (1.7%) was polyspermic. Treatment with ionophore solution yielded a 41.6% incidence of polyspermy (10 of 24 eggs from four tubes) compared with 3.8% polyspermy (1 egg) from the control tubes (P < 0.01). Dispermy was the principal form of polyspermy. The numbers of accessory spermatozoa on/in the zona pellucida were increased by the experimental treatment. Follicular fluid passing down the fallopian tube ampulla at ovulation was therefore considered not to be the physiological stimulus for an initial, tightly-controlled release of spermatozoa from epithelial binding in the caudal isthmus. Indeed, because such sperm activation commences shortly before ovulation, a locally transmitted ovarian programming with relatively high concentrations of follicular hormones remains the favoured model. Although pre-ovulatory progesterone is considered to be the coordinating steroid of increasing influence in these pre-fertilisation events, its effects are proposed to be modulated in the endosalpinx by mobilisation of Ca2+ ions into a discrete population of bound spermatozoa. Results of the steroid-free follicular fluid and calcium ionophore treatments stand in support.
Animals↗
Public policy and state psychiatric hospitals.
Professionals who operate from a clinical rather than a political ethic must be prepared to reclaim and accept leadership roles and responsibilities, which have shifted to the political arena.
Decision Making, Organizational↗
Long-term stability of the bovine block to polyspermy.
Under most circumstances in eutherian mammals, mating occurs before ovulation and a defense against multiple sperm penetration of the zygote is established rapidly after fertilisation. It is generally assumed that this block to polyspermy is both stable and long-lasting, but these points have not been specifically tested. They assume particular significance in domestic farm animals in which procedures of artificial insemination could mistakenly introduce sperm suspensions into a genital tract already containing a fertilised egg. Bovine blastocysts generated in vitro were further exposed in vitro to new suspensions of capacitated bull spermatozoa containing 1.5 x 10(6) cells per ml on days 7 or 8 of development, that is, shortly before or after hatching from the zona pellucida. Inseminated and control blastocysts were examined by light or electron microscopy. Whereas accessory spermatozoa were frequently bound to the surface of the zona pellucida, non had penetrated into the substance of the zona. Similarly, whilst a few spermatozoa had attached to the trophoblast of hatched blastocysts on day 8, none had penetrated through to the blastocoele. No difference was found in the incidence of hatching or rate of expansion between experimental (re-inseminated) and control groups. Accordingly, it is concluded that the bovine block to polyspermy is both stable and long-lasting when tested in vitro in the presence of freshly capacitated bull spermatozoa. Early embryonic loss, which may reach a level of 30% or more in this species, is thus unlikely to be a consequence of instability in the block to polyspermy and accessory sperm penetration of the zygote.
Animals↗
Regional influences of the fallopian tubes on the rate of boar sperm capacitation in surgically inseminated gilts.
Aliquots of ejaculated boar semen containing known numbers of spermatozoa were deposited into the caudal isthmus or rostral ampulla of the Fallopian tubes of gilts at, or immediately after, ovulation to assess regional influences on the rate of capacitation. Eggs were recovered during a second intervention 4, 5, 6 or 7 h after surgical insemination and were examined by phase-contrast microscopy. Results were obtained from ten animals in each of the 4-, 5- and 6-h groups and from eight animals in the 7-h group. With two exceptions, fertilized eggs were not recovered until 6 h after insemination into the isthmus, the proportion (45.6%) being significantly greater than the corresponding figure (1.4%) for ampullary insemination (P < 0.001). Similarly, the proportion of fertilized eggs recovered 7 h after insemination into the isthmus (58.7%) was significantly greater than after ampullary insemination (21.9%; P < 0.01). Numbers of spermatozoa associated with the zona pellucida remained low in all these instances, with mean figures per egg ranging from 0.3 to 3.8. Insemination into the isthmus gave a 1-2 h advantage in fertilization compared with insemination into the ampulla. Although relative rates of sperm cell progression to the site of fertilization may have contributed to this, there is strong evidence that rates of capacitation differ significantly in the respective portions of the Fallopian tube. Therefore, attention was focused on: (1) the viscous glycoprotein secretion in the caudal isthmus acting to remove seminal plasma from the sperm surface; and (2) the phase of sperm head binding to the isthmus epithelium. Gradients in local endocrine modulation by the adjacent ovary offer one explanation for the functional specialization of different regions of the Fallopian tubes.
Animals↗
Have the Fallopian tubes a vital rôle in promoting fertility?
Diverse lines of evidence suggest that the Fallopian tubes make no overwhelming contribution to human reproduction other than as a conduit for gametes and embryos. Even so, bearing in mind global success rates for in vitro fertilization (IVF) coupled with uterine transplantation of embryos (20% fruitful pregnancies), the Fallopian tubes may make a subtle contribution to reproductive performance. The experimental evidence from monkeys and man arguing against an essential rôle for the tubes -- at least in individual instances -- would include (1) the results of Estes' operation, when ovaries are autotransplanted into the uterine lumen in women with blocked or missing Fallopian tubes and pregnancy ensues; (2) asynchronous embryo transfer when newly fertilized (pronucleate) eggs transplanted to the uterus can generate a pregnancy; (3) the transcervical transfer after IVF of early cleavage stage human embryos into the uterus, with subsequent establishment of pregnancy; (4) the trans-cervical transfer of human spermatozoa and oocytes into the uterus to give pregnancy, indicating that capacitation, fertilization and the earliest stages of embryonic development can be achieved in the uterus. In endeavoring to explain contrasts between these successful procedures in primates and their failure in non-primates, perhaps the simplex uterus in primates compared with a bicornuate or bipartite uterus in laboratory and farm species has relevance: there is lack of a clear-cut distinction between the endometrium and endosalpinx in the intra-mural segment and potential mixing of uterine and tubal fluids. Indeed, the latter may explain in part a susceptibility to tubal ectopic pregnancy, coupled with proliferating endometrial fragments in the Fallopian tube.
Animals↗
Deep uterine insemination of cattle: a fruitful way forward with smaller numbers of spermatozoa.
After describing the site of fertilisation and that of the functional sperm reservoir in the female tract, proposals are made concerning a modified site of sperm deposition in cattle. By means of a deep pre-ovulatory insemination into the ipsilateral uterine horn, the chances should be raised of establishing viable spermatozoa in the isthmus where they would undergo a form of physiological encapsulation and storage. Release and activation of such spermatozoa would be prompted by imminent ovulation. Potential advantages of this approach include those of raising the overall fertility of genetically valuable bulls whose non-return rates are sub-optimal; reducing the number of spermatozoa in each insemination dose; using effectively the limited numbers of sex-selected sperm cells (X and Y chromosome bearing spermatozoa) currently available from flow cytometry. Putative disadvantages might include rectal palpation of the ovaries to locate the pre-ovulatory follicle; perforation of the uterine wall by the deep insemination catheter; risk of polyspermic fertilisation; and the inappropriateness of the technique for non-clinically qualified inseminators. Each of these reservations is responded to in a rational manner. Given a change of attitude, a modified technique of insemination would be feasible under commercial conditions and might give a welcome boost to a sagging artificial insemination industry.
Animals↗
Are lower fertility bulls necessarily less fertile? Proposals concerning insemination procedures.
This essay argues that current procedures of selection for high fertility bulls may overlook young males of potentially high fertility unless these are tested by modified procedures of insemination. Should this suggestion prove to be true, even if only for a small proportion of young bulls that would not previously have been retained as stud animals, then valuable production genes would be kept in the national herd. Modified procedures of introducing the sperm suspension might include (I) deep intra-uterine insemination, (II) insemination into the functional sperm reservoir in the Fallopian tube isthmus, (III) laparoscopic insemination close to the utero-tubal junction, (IV) intra-peritoneal insemination, (V) insemination under conditions of mild superovulation, and (VI) insemination with smooth muscle stimulants and/or sperm stimulating agents added to the suspension. (VII) The potential value of in vitro fertilization assays, such as the zona-free hamster oocyte sperm incorporation test, is also noted. Even if only one of these approaches were found to be fruitful, its impact could be of major significance for the cattle breeding industry.
Animals↗
Graafian follicles are cooler than neighbouring ovarian tissues and deep rectal temperatures.
In order to establish appropriate culture temperatures for in-vitro maturation of pig ovarian oocytes, large Graafian follicles (7-10 mm diameter) were sensed by infra-red technology during the latter part of a spontaneous oestrous cycle. Temperatures were measured under systemic anaesthesia almost instantaneously upon revealing the ovaries at mid-ventral laparotomy. Temperature differentials were observed within all 16 ovaries sensed in 14 animals. Ovaries were always cooler than deep rectal temperatures (mean rectal temperature was 38.0 +/- 0.4 degrees C; range 37.5-38.6 degrees C) and mature follicles always cooler than ovarian stroma (35.6 +/- 0.3 degrees C versus 37.3 +/- 0.2 degrees C respectively; P < 0.01). Such follicles were frequently 1.5-1.8 degrees C cooler than the adjacent stroma, the mean being 1.7 +/- 0.4 degrees C. Small Graafian follicles (< 5-6 mm diameter) and recent ovulations did not show this differential. The control experiment of excising an ovary, deep freezing it in liquid nitrogen, and then restoring it to the body cavity before further sensing indicated that intra-ovarian temperature gradients depended on the activity of living tissues and/or a functional blood supply. Furthermore, calculation of anticipated rates of cooling for exposed Graafian follicles strongly suggested that artefacts could not have been solely responsible for the observed temperatures. Endothermic reactions within mature follicles were thus brought into focus. It is concluded that follicular temperatures may influence the meiotic progression and cytoplasmic maturation of oocytes and act to regulate enzymatic activity in the biosynthetic pathways for steroid and/or peptide hormones.
Animals↗
Motility of spermatozoa in hydrosalpingeal and follicular fluid of pigs.
Hydrosalpinges were created to collect adequate volumes of fluid during pre-, peri- and postovulatory intervals from the ampulla, ampullary-isthmic junction and the isthmic-utero-tubal junction of the oviducts from Large White gilts that had exhibited at least two natural oestrous cycles. The accumulated fluids, follicular fluid and Butschwiler's medium were compared for their effects on various parameters of boar sperm motility using the CellSoft, computer-assisted, digital image analysis system. Sperm velocity (micron s-1 +/- SEM) was significantly higher (P < 0.05) in follicular fluid (84 +/- 3; n = 5) than in fluids from the ampulla during peri- and early postovulatory intervals, and from the isthmic-utero-tubal junction during pre- and early postovulatory intervals. It was also higher (P < 0.05) than in the fluid from the ampullary-isthmic junction during pre- and early postovulatory intervals; however, sperm velocity in follicular fluid was not significantly different from that in the periovulatory fluid from the ampullary-isthmic junction. The mean lateral head displacement (ALHmean) of spermatozoa was significantly greater in follicular fluid (3.9 +/- 0.3 microns; n = 5) than in fluid from the ampulla during peri- and early postovulatory intervals and from the isthmic-utero-tubal junction during pre- and early postovulatory intervals, and was also higher (P < 0.05) than in fluid from the ampullary-isthmic junction during the preovulatory period, but was not different from the peri- and postovulatory ampullary-isthmic junction fluids. The proportion of spermatozoa exhibiting circular motion was significantly higher (P < 0.05) in the periovulatory fluid from the ampullary-isthmic junction (24 +/- 3%) compared with fluids obtained during preovulatory and early postovulatory periods. Follicular fluid had no effect on the proportion of spermatozoa exhibiting circular motion. The average radius of sperm movement in circular trajectories was higher in follicular fluid than in the periovulatory fluids from the ampulla and ampullary-isthmic junction (P < 0.05). In hydrosalpingeal fluids collected 2-5 days after ovulation, the average radius of movement was greater in the ampulla fluid and ampullary-isthmic junction fluid than in fluid from the isthmic-utero-tubal junction (P < 0.05). These results demonstrate that follicular fluid and oviductal fluids have considerable influences on boar sperm motility. Furthermore, the immediate effect of periovulatory ampullary-isthmic junction fluid in increasing the percentage of spermatozoa swimming in circles (hyperactivated) is relevant, since it is at this time and within this region that fertilization occurs.
Animals↗
Oviduct fluid pH in intact and unilaterally ovariectomized pigs.
The pH of the oviduct lumen was measured at different stages of the estrous cycle in the ampulla and ampullary-isthmic junction (AIJ) of intact and unilaterally ovariectomized mated or nonmated pigs. The pH profile consisted of high frequency small peaks superimposed on low frequency large amplitude peaks. One animal examined at midcycle exhibited fluctuations in pH (peak to nadir; delta pH) of 0.3 and 0.7 units in the ampulla and AIJ, respectively, and the frequencies of the large peaks in these regions were 2.6 and 1.6 peaks.min-1, respectively. In six preovulatory unmated pigs, the delta pH (mean +/- SE) was 0.50 +/- 0.04 units in both regions and the large peak frequencies were 0.6 +/- 0.06 peaks.min-1. In one animal that was assessed during ovulation, the pH showed deviations of up to 0.4 pH units, which were probably due to the alkalinity of follicular fluid accompanying the ovulated eggs. In the ampullae of five unilaterally ovariectomized postovulatory-mated pigs, the delta pH in oviducts with and without an ipsilateral ovary was significantly lower than preovulatory (p < 0.05), but the large and the small peak frequencies were not significantly different. By contrast, the delta pH in the AIJ with an ipsilateral ovary (0.11 +/- 0.02 units) was significantly lower than before ovulation (0.54 +/- 0.04 units) and also when compared with the contralateral AIJ (0.36 +/- 0.06 units) (p < 0.05). The ovary also influenced the small peak frequency, which was significantly higher if the ipsilateral ovary was absent (10.7 +/- 1.5 vs. 14.9 +/- 1.6 peaks.min-1, respectively). Thus, oviduct fluid pH is controlled by both systemic and local mechanisms, and the ipsilateral ovary and (or) embryonic factors influence the pH profile of the oviduct.
Animals↗
Ovarian control of very low sperm/egg ratios at the commencement of mammalian fertilisation to avoid polyspermy.
This essay considers the means whereby sperm/egg ratios close to unity are generated during the initial stages of fertilisation in placental mammals. Pre-ovulatory graafian follicles and their contents are seen to be key structures orchestrating the events of sperm progression and coordinating the subsequent meeting of male and female gametes. Three levels of control over the numbers of spermatozoa activated and released from the functional reservoir in the caudal region of the fallopian tube isthmus are proposed. A primary control would be obtained by means of a countercurrent transfer of ovarian follicular progesterone from the ovarian vein into the tubal branch of the ovarian artery. The concentration of progesterone so transferred would be proportional to the number of preovulatory follicles, and thus to the number of eggs to be shed, and would act progressively to reduce sperm binding to the endosalpinx of the caudal isthmus. Differential timing of the release from epithelial binding may be a crucial means of achieving the initial low sperm/egg ratios. a secondary regulation of the release of graded numbers of viable spermatozoa towards the ampullary-isthmic junction of the fallopian tubes would be by means of molecular messages derived from the mucified oocyte-cumulus complex shortly before and after the time of ovulation. Third would be reorientation of sperm trajectories by molecular gradients within the cumulus cell mass to direct competent spermatozoa to those oocytes as yet unpenetrated. Together these differing levels of control would impose low sperm/egg ratios during the initial stages of fertilisation, such strict quantitative regulation of male gametes lasting at least until the block to polyspermy is fully established and the vitellus is no longer at risk from further sperm penetration.
Animals↗
Aetiology of intersexuality in female (XX) pigs, with novel molecular interpretations.
This review considers the problem of ovotestis formation in animals of 38,XX chromosome complement. After a clinical description, attention focuses on the condition of the gonads and genital tract. A complete spectrum of gonadal types has been found, ranging from a single ovotestis almost invariably on the right-hand side to both gonads appearing as testicular-like structures, sometimes with a distinct tunica albuginea. The ovotestis or testis-like structure may have descended to an inguinal or scrotal location. Although interstitial cells of Leydig and seminiferous tubules were always abundant in testicular tissue, germ cells were never present. The lumen of the seminiferous tubules was packed with pale-staining, Sertoli-like cells. A bicornuate uterus was characteristic but suppression of the proximal portion of the Müllerian duct always adjoined an ovotestis; a corresponding development of the Wolffian duct featured as a convoluted epididymis. Inhibition of the Fallopian tube was attributed to a local influence of AMH from the Sertoli cells, as was the failure of small Graafian follicles within an ovotestis to respond to injected gonadotrophins. As to the aetiology of an ovotestis, defective colonisation of the genital ridges by primordial germ cells is considered, as is evidence for incorporation of adrenal cells into the embryonic gonad. Molecular probing has failed to reveal the classical sex-determining gene, Sry, and other Y-related DNA sequences such as Zfy and DYZI in almost all the intersex animals examined. Currently favoured as an explanation for ovotestis formation is a mutation in the inhibin gene within granulosa cells of Graafian follicles. Such a mutation would prompt secretion of the closely comparable glycoprotein molecule AMH in these genetic females, with a resultant progressive virilisation of gonadal tissue. The proposed mutation may be carried as an autosomal recessive gene by certain boars. Varying amounts of AMH secretion or differing timescales for the transition from inhibin to AMH could in part explain differing degrees of ovotestis formation. Despite this proposition, interactions between genes that prescribe functional testicular tissue, enhanced rates of gonadal development, and left-right asymmetries between the paired gonads now require systematic study.
Animals↗