Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Freemartinism”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1982

[Twins in cattle. Freemartin or not a freemartin? Preliminary Communication].

The preliminary results of comparative studies designed to make it possible to establish a diagnosis of 'freemartin' are reported. Three methods were used, namely typing of the blood, chromosome analysis and determination of the length of the vagina. In a very large number of cases, the diagnosis may even be established in very young calves by measuring the length of the vagina. Laboratory studies may provide a solution in doubtful cases.

Animals↗
PubMed2001

Inter-relationships among gonadotrophins, reproductive steroids and inhibin in freemartin ewes.

Freemartins are sterile XX/XY chimaeras that occur as a result of placental fusion between male and female fetuses during early pregnancy. Freemartins occur predominantly in cattle, although the prevalence of ovine freemartinism is increasing. In this study, the reproductive endocrinology of ovine freemartins was compared with that of normal sheep. Freemartins had significantly (P < 0.001) higher basal concentrations of LH and FSH than did normal ewes or rams, although the response of LH to GnRH (10 microg) was similar in freemartins, ewes and rams. Resting concentrations of oestradiol were similar in freemartins and ewes and were increased in both after eCG administration. Testosterone concentrations were higher in freemartins than in ewes, but were unresponsive to GnRH or eCG. Administration of 62.5 mg progesterone or 25 lg oestradiol twice a day for 3 days suppressed LH concentrations to baseline values in freemartins, ewes and rams. In ewes, 500 microg oestradiol administered twice a day caused preovulatory surges in LH concentrations, but suppressed LH in freemartins to baseline values. Thus, LH secretion can potentially be regulated in freemartins by gonadal steroids. FSH concentrations in freemartins were not suppressed by doses of inhibin that were effective in ewes and rams. Therefore, freemartins behave in part like castrated animals, as they have high basal concentrations of LH and FSH, which can be stimulated by GnRH and suppressed by gonadal steroids. Conversely, inhibin does not suppress FSH concentrations in freemartins, and freemartins have circulating concentrations of steroids intermediate between those of castrated and normal animals.

Animals↗
PubMed2004

The freemartin syndrome: an update.

The freemartin condition represents the most frequent form of intersexuality found in cattle, and occasionally other species. This review considers the current state of knowledge of freemartin biology, incidence, experimental models, diagnosis, uses for freemartins in cattle herds, occurrence in non-bovine species, effects on the male, and highlights potential new research areas. Freemartins arise when vascular connections form between the placentae of developing heterosexual twin foeti, XX/XY chimerism develops, and ultimately there is masculinisation of the female tubular reproductive tract to varying degrees. With twinning rates in Holstein cows increasing, there will be greater economic importance to establish early diagnosis of the freemartin and the detection of the less common single born freemartin. New diagnostic methods based on the detection of Y-chromosome DNA segments by polymerase chain reaction (PCR) show improved assay sensitivity and efficiency over karyotyping and clinical examination. The implications for the chimeric male animal born co-twin to the freemartin are contentious as to whether fertility is affected; if germ cell chimerism does indeed occur; and, if there are any real effects on the sex ratio of offspring produced. In beef cattle, the freemartin carcass has similar characteristics to normal herdmates. Hormonal treatment of freemartins for use as oestrous detectors has been used to obtain salvage value. The biology of freemartin sheep has recently been studied in detail, and the condition may be increasing in prevalence with the introduction of high fecundity genes into flocks. Potential new research areas are discussed, such as detection of foetal DNA in maternal circulation for prenatal diagnosis and investigation of the anti-tumour properties of Mullerian inhibiting substance (MIS). The freemartin syndrome will always be a limiting factor in cattle and to a lesser extent in sheep production systems that have the goal to produce multiple reproductively normal female offspring from a single dam without using sex predetermination.

Animals↗
PubMed1994

Diagnosis of freemartinism in cattle: the need for clinical and cytogenic evaluation.

A total of 727 blood samples from female calves born co-twin to male calves were examined cytogenetically for freemartinism between 1978 and 1992. Six hundred calves (82.5%) were determined to be freemartins, and 127 (17.5%) were determined not to be freemartins. The percentage of calves determined not to be freemartins was substantially higher than the 8% reported for an unselected population of female co-twins. We concluded that some obvious freemartins were eliminated prior to submission of samples for confirmatory cytogenetic diagnosis, and that only a small percentage of the estimated 93,000 female calves born co-twin to male calves annually are so examined. Therefore, probably a large number of female co-twins that are not truly freemartins are sold to slaughter every year. We propose that obvious freemartins be identified by use of the vaginal-length test and that the remaining clinically questionable calves be differentiated cytogenetically. This combination of procedures could prevent unnecessary economic losses and preserve important genetic material. Three animals with chromosomal anomalies were found during examination of samples for freemartinism. Cytogenetic evaluation for freemartinism thus offers the added value of simultaneous surveillance for cytogenetic aberrations in male and female cells of a sample.

Animals↗
PubMed1995

Development of the gubernaculum and processus vaginalis in freemartinism: further evidence in support of a specific fetal testis hormone governing male-specific gubernacular development.

BACKGROUND: Freemartinism occurs in some species of ruminants and affects most female bovine fetuses in heterosexual, multiple pregnancies owing to fusion of the chorionic blood circulations soon after implantation. Maldevelopment of the ovaries and Müllerian ducts have been described and recognized as resulting from exposure of their respective primordia to an excess of anti-Müllerian hormone. The present study aimed to analyse the prenatal growth and development of the gubernaculum in freemartins to find out its possible affliction through foetal testis hormones derived from their male co-twin. METHODS: Histological sections of young and drawings and photographs of further developed freemartins and control male and female bovine foetuses were analysed. The specimens had been collected earlier for analysis of the time course of male and female gonadal and genital development and its impairment associated with freemartinism. RESULTS: The gubernaculum of 35-40-day-old male and female fetuses was in the initial stage of development and of similar appearance in all specimens. Gubernacula of 60-70-day-old male fetuses differed from those of females of similar age in various respects: the male gubernaculum size was larger and extension of the processus vaginalis was deeper. Freemartins showed an intermediate development with some individuals resembling male and others resembling female agemates. During further development, gubernacula in males developed into muscular cremaster sacs, whereas those in females generally did not develop beyond the size and structural complexity of 70-day-old foetuses. Beyond day 70 of fetal life, gubernaculum development in freemartins definitely showed male characteristics with respect to size and growth of a processus vaginalis with a cremaster muscular wall. The male-like pattern of the outgrowth of the processus vaginalis changed during the second half of prenatal life. Rather than its further deepening as in males, this structure became inverted to become emerging as a papilla-like structure from the inguinal abdomen bottom. An explanation is proposed for this unprecedented inversion, taking into account: (1) the faster and higher reaching rightsided ascent of the kidneys and gonads, (2) the femalelike outgrowth of the cranial gonadal suspensory ligaments, and (3) the absence of scrotum development. The ovaries and mesonephric remnants in developing freemartins, during their ascent together with the kidneys while remaining attached to the bottom of the developing processus vaginalis sacs via the gubernaculum ligament, are proposed to act together to pull up the bottom of the processus vaginalis sacs. From this action, "inverted hernia sacs" result as the irreversible consequence. CONCLUSION: The data support the concept that foetal testes act, via as an yet unidentified third hormone, to establish malelike development of gubernacula into muscular cremaster sacs. Further work is required to reveal the identity of this hormone. Furthermore, the apparent similarity of the freemartins' inverted processus vaginalis sacs and the fetal rodents' gubernacular cones suggests that the ruminants' and rodents' processus vaginalis are essentially similar structures. Thus there is no longer an urgent need to distinguish between two different types of gubernaculum development and testis descent in rodents and ruminants, respectively, and involving or not fetal gubernacular cones. The present observations may thus contribute to the development of a unified hypothesis for sexually dimorphic development of the gubernaculum throughout the mammalian class.

Androgens↗
PubMed1980

Serum-borne H-Y antigen in the fetal bovine freemartin.

In mammals, ovarian cells that have been exposed to soluble H-Y antigen acquire the H-Y+ cellular phenotype. They absorb H-Y antibody in serological tests. To determine whether masculinization of the bovine freemartin, the synchorial female twin of a bull, could be due to attachment of circulating bull-twin-derived H-Y in the freemartin gonad, we exposed normal fetal ovarian cells to serum from fetal bulls, fetal cows and fetal freemartins. Ovarian target cells became H-Y+ after exposure to serum from fetal bulls or fetal freemartins, but not after exposure to serum from fetal cows. In a new competitive binding radioassay, uptake of Daudi-secreted tritiated H-Y was inhibited in fetal ovarian target cells first exposed to mouse testis supernatant, a demonstrated source of soluble H-Y. It was also inhibited in ovarian target cells exposed to serum from fetal bulls or fetal freemartins; uptake was unaffected by exposure to serum from fetal cows. Since Daudi-secreted H-Y is known to induce precocious testicular organogenesis in XX indifferent gonads in culture, we infer that initial transformation of the freemartin gonad is due to H-Y antigen that is secreted in the fetal bull, transmitted in the common chorionic vasculature and bound by gonadal receptors of the fetal cow.

Animals↗
PubMed1999

Birth of a Holstein freemartin calf co-twinned to a schistosomus reflexus fetus.

An unusual case of a live Holstein freemartin calf co-twinned with schistosomus reflexus fetus is presented here. Delivery of the schistosomus reflexus was achieved by fetotomy 24 h after manual delivery of a live heifer calf. The dam subsequently experienced concurrent metritis and left displacement of the abomasum; however, she conceived following insemination 85 d post partum. Cytogenetic examination of the live heifer using lymphocyte culture and cutaneous fibroblast cell culture failed to demonstrate chromosomal chimerism, whereas polymerase chain reaction (PCR) detected the presence of the bovine Y-chromosome marker BRY-1. Low concentrations of testosterone, estradiol and progesterone at 3, 6, 24 and 48 h after administration of hCG were detected in the serum of the freemartin heifer. Genetic, hormonal, histological and clinical findings established the live female co-twin calf was a freemartin, an abnormality of phenotypic sex. Failure to detect any significant peripheral concentrations of androgen supports the hypothesis that masculinization of the freemartin reproductive tract arises from diffusion of androgen and possibly other substances from the male co-twin rather than from endogenous production of androgen within the freemartin. This report documents that the freemartin condition can be induced by a male fetus with severe developmental abnormalities.

Abdomen↗
PubMed2003

Morphological, histological and histochemical studies of the gonads of ovine freemartins.

Freemartins are XX/XY chimaeras that develop as a result of the fusion of the placental circulation of at least one male and one female fetus. Of 19 freemartin ewes, 13 had testis-like structures, seven of them in an abdominal position and six in an inguinal position. Histologically, their gonads had structures resembling seminiferous tubules and interstitial cells, and grossly, most had structures derived from the mesonephric ducts (vasa deferentia, epididymides and vesicular glands). The other six freemartin ewes had small, undifferentiated gonads that lacked either follicles or seminiferous tubule-like structures. They also lacked any structures derived from the mesonephric ducts. No derivatives of the paramesonephric ducts were detectable in any of the freemartin ewes. The gonads of the male-type freemartins stained immunocytochemically for 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and histochemically for alkaline phosphatase (AP) in a similar way to, but more extensively and intensely than, the gonads of normal rams, and the staining was confined to interstitial cell-like structures. The staining in the undifferentiated-type freemartins was weak, but both 3beta-HSD and AP were present in unidentified cell types.

3-Hydroxysteroid Dehydrogenases↗
PubMed2007

Explaining the freemartin: Tandler and Keller vs. Lillie and the question of priority.

The correct explanation for the freemartin phenotype in the female twin of a female-male pair in cattle was first reported by Tandler and Keller (1911. Deutsche Tierärzt Wochenschr 19:148-149). This same explanation for the freemartin was independently discovered by Lillie (1916. Science 43:611-613). Today both set of scientists are given credit for this discovery; it is the basis for much of the subsequent work on the developmental basis for sex differentiation in vertebrates. Even though Lillie published after Keller and Tandler, he gets credit for this discovery because: (1) Keller and Tandler published in a veterinary journal and as a consequence their work was not disseminated as broadly throughout the larger scientific community; this problem was compounded by the fact that their definitive 1916 paper was published under wartime conditions during World War I, and (2) Lillie was an influential scientist with a group of graduate students who could elaborate on and extend his work; they published a number of papers on the freemartin. At some point while Lillie was doing his initial work on the freemartin he may have become aware that Keller and Tandler were also working on the freemartin problem; this information may have shaped his decision on when to publish.

Animals↗
PubMed1994

Retrospective studies on the measurements, karyotyping and pathology of reproductive organs of bovine freemartins.

A retrospective study of 217 cases of bovine freemartinism was made. Of these, 14 cases were diagnosed clinically, 141 were karyotyped and 62 were subjected to macroscopical examination of the reproductive tract. Of the 62 cases, 43 were assessed by measuring the reproductive organs (size and/or weight) and 41 were examined microscopically. Complete information on gross, histopathological and karyotyping analysis was available for only 10 animals. Freemartins showed reduced measurements of all reproductive organs. The mean lengths of vulva and vagina were 6.4 cm and 8.1 cm, respectively. Vesicular glands were observed in 30 freemartins. Histologically, these glands had more fibrous and less glandular tissue than the normal male vesicular glands. Uterine changes were variable, ranging from aplasia (two animals) to normal. Likewise, endometrial glands ranged from hypoplastic (decreased number and size) to normal. Glandular and myometrial cells showed prominent nuclei and less than normal cytoplasm, indicating a non-functional status. Gonadal size was reduced and an epididymis was present in seven animals. Rete ovarii were prominent and frequently occupied two-thirds of the gonad. Undifferentiated sex cords and abundant interstitial cells were salient features of the freemartin gonad. Oocytes were not observed. Ovarian follicles were seen in six cases. Karyotypic analyses demonstrated XY chimaerism in all freemartins.

Animals↗
PubMed1981

Reproductive anatomy and cytogenetics of freemartin heifers.

Out of a batch of 46 heifers obtained for breeding 19 were found to be freemartins by both anatomical and cytogenetic examination. Considerable variation existed in the reproductive tracts of these freemartins from structures that were essentially female to some that were essentially male in type. One heifer had a functional ovary containing a corpus luteum and had shown signs of oestrus. Sex chromosome chimaerism was detected in cultured leucocytes and in bone marrow from each of the freemartins, ranging from 2 per cent to 96 per cent male cells. Chimaerism was also detected in cell cultures from spleen, lung and gonad but at very low levels (less than 2 per cent male cells). None of the freemartins consistently showed the presence of male cells in all organs cultured. The problem of the clinical diagnosis of freemartins is discussed in relation to these results.

Animals↗
PubMed1977

Sex-chromosome ratios in cattle and their relationship to reproductive development in freemartins.

Nineteen "female" Holstein-Friesian calves born co-twin with a bull were purchased shortly after birth. One subsequently was judged to be a normal female with 0% XY (100% XX) karyotypes in cultures of blood lymphocytes. However, one typical freemartin also had 0% XY (100% XX) Karyotypes in 300 cells when examined at three ages. Overall, 18 freemartins examined at 1, 24, and 52 weeks of age averaged 60.7%, 57.9%, and 55.5% XY cells, respectively (P greater than 0.05). No systematic relationship was found between the proportion of XY cells and the abnormalities of the reproductive organs, as judged by vaginal depth and clitoral development at 1, 24, and 52 weeks, and examination of the reproductive organs per rectum at 54 weeks of age. The clitoris of untreated freemartins and those treated with estrone or estradiol postnatally did not enlarge. Testosterone treatment caused enlargement. None of the hormones affected vaginal depth. These studies provide convincing evidence that the blood lymphocyte XX:XY karyotype ratio (1) is not related to the degree of masculinization and (2) is stabile in the postnatal freemartin. Thirdly, the freemartin reproductive organs do not respond to common sex-steroid hormones postnatally other than the clitoral response to testosterone.

Animals↗
PubMed1981

Altered steroidogenesis by the fetal bovine freemartin ovary.

Ovaries were taken from 12 freemartins of crown-rump length 4.2-27.5 cm (47-130 days of gestation), 16 singleton fetuses of 5-8 cm (55-75 days) and 18 single fetuses of 10-20 cm (78-108 days). Ovaries were incubated for 24 h in tissue culture Medium 199 supplemented with 5% calf serum. The freemartin ovaries produced 0.16-2.1 ng testosterone/ovary/24h compared with less than 50 pg for normal singleton ovaries. Oestrogen was undetectable n the ovaries (less than 50 pg) of freemartin fetuses of crown-rump length 4.2-9.4 cm (47-77 days), while 16 normal ovaries of the same stage produced 1375 +/- 300 pg/ovary/24 h. The presence of abnormally high amounts of testosterone and the absence of normally occurring oestrogen in the freemartin ovary indicate that the pattern of steroidogenesis in the freemartin is altered as early as 47 days of gestation.

Animals↗
PubMed1984

Origin of anti-Müllerian hormone in bovine freemartin fetuses.

The origin of AMH responsible for Müllerian duct regression in bovine freemartins has been reinvestigated, using a sensitive RIA for this hormone. Between 50 and 80 days, Müllerian duct regression occurs simultaneously in males and freemartins. Both twins exhibited high and positively correlated serum AMH concentrations, whereas gonadal in-vitro production of AMH and biological anti-Müllerian activity were detectable at a low level only in 2 out of 13 freemartins. In the gonads of approximately half the freemartins after 80 days, seminiferous tubules differentiated and the gonads produced AMH, but the output was very low compared to that of the male twin. These data suggest that regression of Müllerian duct in freemartins is essentially mediated by AMH produced by the testes of the male twin.

Animals↗
PubMed1981

Sample size for detection of Y-chromosomes in lymphocytes of possible freemartins.

The number of metaphases that need to be examined to detect a Y-chromosome in a lymphocyte of a possible freemartin with a prescribed degree of certainty depends on the distribution of % XY cells among freemartins. To quantify this, the beta-binomial distribution was fit by maximum likelihood to% XY cells observed in blood samples of 70 freemartins (twin births only). The estimate mean and standard deviation of XY cells frequency in 70 freemartins (12,885 metaphases) was 0.48 and 0.30, respectively. These estimates correspond to a U-shaped distribution of XY cell frequency, i.e., one in which either an XX or an XY cell type predominates in most freemartins. These values indicate that sample sized of 26 and 168 are required to by 95% and 99% confident, respectively, that a female co-twin will not be misclassified.

Animals↗
PubMed1984

Foetal testicular steroidogenesis and responsiveness to LH in freemartins and their male co-twins.

Foetal gonads were obtained from 1) 8 male foetuses that were co-twin to freemartins, 2) 8 isosexual twins, 3) 59 singletons of 45-75 days of gestations, 4) 5 isosexual and 5 male co-twins of 90-120 days and 5) 5 freemartins at 70-120 days of gestation. The gonads were incubated in supplemented medium 199 for 24 h in the absence or presence or LH and the testosterone and progesterone produced measured by RIA. During the time of sexual differentiation (45-75 days) the testes of the male co-twins produced significantly less testosterone than testes from isosexual or singletons of the same age. Testes of foetuses older than 90 days were refractory to LH-stimulation, but freemartin ovaries and testes from their male co-twins continued to respond to LH with increased testosterone production. No significant differences in progesterone production were detected amount co-twins, isosexual twins or singletons at any age. We conclude that the testes of the male twin that is co-twin to a freemartin displays abnormal steroidogenesis. This may be related to reports of abnormal testes after birth in males co-twin to freemartins.

Animals↗
PubMed2003

Morphological, histological and histochemical studies of the pituitary glands of ovine freemartins.

Freemartins are XX/XY chimaeras that develop as a result of the fusion of the placental circulation of at least one male and one female fetus. The pituitary glands of eight normal ewes at various stages of the oestrous cycle and three rams were compared with those of two male-type and three undifferentiated-type freemartins. The pituitaries were heaviest in the male-type freemartins, and their pattern of gonadotrophs, assessed by differential staining, was more intense than in the normal males. The pituitaries of the undifferentiated-type freemartins weighed less than those of the normal ewes but had more stained gonadotrophs than the normal ewes or rams. In both types of freemartins the pattern of cells resembled that of a castrated male.

Animals↗
PubMed1999

The diagnosis of freemartinism in cattle using sex-specific DNA sequences.

The majority of heifers born co-twins to bulls are infertile freemartins. It is important that the condition be diagnosed at an early age as freemartins have no potential for use as replacement stock. A rapid, robust, reliable technique for freemartin diagnosis is described. Three Y-specific polymerase chain reaction (PCR) primer pairs: BOV97M, BRY.1 and AMX/Y were used to detect male cells in the blood of heifers born co-twins to bulls. PCR -based tests have advantages over currently used methods of freemartin diagnosis.

Animals↗