The effect of estrogen receptor genotype on litter size and placental traits at term in F2 crossbred gilts

The effect of estrogen receptor (ESR) genotype (two alleles, A and B) on litter size of 275 Large White x Meishan F2 crossbred gilts (73 AA, 126 AB and 76 BB gilts) was tested. In addition, for 63 of these gilts (18 AA, 24 AB, and 21 BB) the effect of ESR genotype on average placental traits at term was tested, since individual placental information was available for 88% of the 628 liveborn piglets. Without affecting average birth weight of the piglets, ESR genotype significantly affected litter size, i.e. AB gilts had larger litters than BB gilts (P < 0.05). Total number born was 11.38+/-0.38, 11.88+/-0.28, and 10.68+/-0.35, while number born alive was 10.45+/-0.39, 11.07+/-0.29, and 9.85+/-0.36 for AA, AB and BB gilts, respectively. Since the B allele in previous research was associated with largest litters, the hypothesis that ESR is a marker rather than the major gene itself is discussed. Average placental length, surface area, and weight including and excluding amnion were not affected by ESR genotype. However, placentae of AB gilts had a significantly lower number of areolae per placenta than BB gilts and had a lower number of areolae/cm2 placenta than AA and BB gilts. Number of areolae was 8945+/-663, 7240+/-619, and 9694+/-633, for AA, AB and BB gilts, respectively. Although the reason for the low number of areolae on placentae in AB gilts is not yet known, the results suggest that the ESR linked major gene for litter size might be involved in the development and activity of endometrial glands.     

Fetal and placental traits at day 35 of pregnancy in relation to the estrogen receptor genotype in pigs

Fetuses from gilts with estrogen receptor (ESR) genotype AA (AA-AA and AA-AB) and BB (BB-AB and BB-BB) were compared at Day 35/36 of pregnancy, to examine whether fetal ESR genotype nested within maternal ESR genotype would affect fetal traits. Furthermore the relation of fetal body weight and fetal heart weight to various placental traits were evaluated relative to ESR genotype. Fetal and placental weight and length, and implantation surface area were not affected by fetal ESR genotype nested within maternal ESR genotype. Fetal weight was related similarly to placental length, placental weight, and implantation surface area: up to a certain threshold value (40 cm, 40 g and 250 cm2, respectively), an increase in the trait was associated with an increase of fetal weight. Thereafter, fetal weight did not change anymore. Thus, at Day 35/36 of pregnancy porcine fetuses seem to have a maximum growth potential. The percentage of AA-AA fetuses that had not reached this maximum growth potential was larger than of the other three genotype combinations studied, and therefore a higher subsequent fetal mortality may be expected in this group. Hearts of AA-AB fetuses were significantly heavier than those of BB-AB and BB-BB fetuses and tended to be heavier than those of AA-AA fetuses. The reason for this hypertrophy is unclear, but might be related to a difference in placental vascularity. Heart weight of fetuses from BB gilts increased with fetal weight, while heart weights of fetuses from AA gilts did not. Heart weight increased with an increase of placental length and implantation surface area up to 51 cm and 437 cm2, respectively, and thereafter decreased again. For BB-AB fetuses a similar relation was found between heart weight and placental weight, while heart weight of the other three genotype combinations remained unaffected as placental weight increased. The fetus and placenta are continuously changing during early pregnancy, therefore different mechanisms may change the demands for cardiac output. However, keeping in mind that placental size and blood volume are relatively large, placental vascularity and vascular development may play a major role. Therefore, further research on heart size, placental size and vascularity, relative to ESR genotype, is recommended.     

Parturition in gilts: duration of farrowing, birth intervals and placenta expulsion in relation to maternal, piglet and placental traits

Large White x Meishan F2 crossbred gilts (n = 57) were observed continuously during farrowing while the placentae of their offspring were labeled in order to examine the duration of farrowing and placenta expulsion in relation to maternal-, piglet- and placental traits and the duration of birth interval in relation to birth weight, birth order and placental traits. Independently from each other, litter size, gestation length and offspring directed aggression significantly (P 0.05) affected duration of farrowing. An increase in litter size was associated with an increase of duration of farrowing and an increase in gestation length was associated with a decrease of duration of farrowing. Aggressive gilts took longer to farrow, compared to non-aggressive ones. After taking into account litter size, gestation length and offspring directed aggression, placental thickness (i.e., placental weight corrected for placental surface area) was significantly (P < 0.05) related to duration of farrowing, i.e., litters with on average thicker placentae took longer to farrow. The latter effect is the result of the fact that individual placental thickness significantly (P < 0.01) affected individual birth interval, independent of birth weight. The piglet has to break its own membranes to be able to start its journey through the uterus towards the birth channel. Apparently, a thicker placenta offers more resistance and thus prolongs the process of birth. Independent of placental thickness, birth interval significantly (P < 0.01) decreased with an increase in birth order (first born to last born). The high variation of birth intervals for the last born piglets, caused a slight increase in average birth interval for the latter piglets. Litters with on average more areolae per placenta took significantly (P < 0.001) less time to be born than litters with on average less areolae per placenta (independent of total number of piglets born and other placental traits), while birth intervals within litters were not affected by this trait. Thus, these results are probably due to a gilt trait rather than a piglet trait. Since the number of areolae represent the number of uterine glands present, the gilt trait might be uterine development. Duration of placenta expulsion significantly (P < 0.01) increased with an increase of duration of farrowing. Furthermore, the first placenta was expelled significantly (P < 0.01) earlier relative to last piglet when duration of farrowing was protracted, while there was no relation of the time interval between first placenta and last piglet and the duration of placenta expulsion. In conclusion, the most important finding of this study is that placental thickness rather than birth weight appears to play an important role in the duration of birth intervals and as a result, of duration of parturition in gilts.     

Changes in the binding of angiotensin II to rat placental receptor by estrogen and progesterone

The effects of estradiol and progesterone on the binding of rat placental angiotensin II receptors were examined. Sex steroid (progesterone estradiol plus progesterone) decreased the total number of rat placental angiotensin II receptors, while sex steroid (estradiol plus progesterone) increased angiotensin levels. Our present results suggest that sex steroids may play an important role in the control of the number of the angiotensin binding sites during pregnancy.     

Litter size and piglet traits of gilts with different prolactin receptor genotypes

Seventy-seven Large White x Meishan F2 crossbred gilts with prolactin receptor (PRLR) genotype AA (n = 26), AB (n = 36) and BB (n = 15) were compared for teat number (FTm), age at first estrus, gestation length (GL), litter size, and litter means of functional teat number (FTp), birthweight (BW), and pre-weaning growth rate (GR). Own placental information was available for 88% of 620 live-born piglets (62 gilts), since placentae were labeled during farrowing. The effect of PRLR genotype of the mother on average placenta weight (PLW) and placenta efficiency (EFF = BW/PLW), was therefore, also analyzed, PRLR genotype significantly (P < 0.05) affected age at first estrus and, as a result (since the gilts were inseminated at a fixed estrus number), age and bodyweight at insemination. Furthermore, PRLR genotype affected total number of piglets born (TNB, P = 0.056) and number of piglets born alive (NBA, P = 0.072), but it did not affect (P > 0.3) GL, BW or GR, neither before nor after correction for litter size. BB gilts were significantly younger at first estrus and younger and lighter at insemination than AA gilts (P < 0.05). AA gilts had larger TNB (P = 0.047) and tended to have a larger NBA (P = 0.062) than BB gilts. TNB was 11.4 +/- 0.7, 10.8 +/- 0.6, and 8.8 +/- 0.9; NBA was 11.1 +/- 0.6, 10.5 +/- 0.6, and 8.7 +/- 0.9; BW was 1309 +/- 40, 1277 +/- 34, and 1290 +/- 53 g; and GL was 113.6 +/- 0.3, 113.8 +/- 0.3, and 113.5 +/- 0.4 days for AA, AB and BB gilts, respectively. The effects on litter size and age at first estrus are independent effects. PRLR affected PLW (P = 0.050) and EFF (P = 0.066), resulting in a difference between AA and BB gilts. PLW was 160 +/- 9, 181 +/- 7 and 196 +/- 11 g and EFF was 7.6 +/- 0.2, 7.3 +/- 0.2 and 6.7 +/- 0.3 for AA (n = 19), AB (n = 29) and BB (n = 14) gilts, respectively. After correction for TNB, the differences disappeared. Functional teat number of the AA. AB and BB gilts was 15.35 +/- 0.22, 15.53 +/- 0.18, and 15.60 +/- 0.29, respectively, and was not affected by PRLR genotype (P = 0.7). Functional teat number of piglets from AA, AB and BB mothers was 14.20 +/- 0.10, 14.37 +/- 0.08, and 14.63 +/- 0.13, respectively. Piglets from BB mothers had on average larger numbers of functional teats compared to piglets from AA mothers (P = 0.028). In conclusion, PRLR gene is a major gene or marker for age at first estrus, litter size, and litter average of number of functional teats in the Large White x Meishan F2 crossbred gilts studied. The favorable allele for litter size (A allele) is the unfavorable allele for age at first estrus and for litter mean of functional teat number.     

Oestrous behaviour in relation to fertility and fecundity of gilts

The reproductive performance of 2484 gilts was recorded over a 12-month period at a large intensive piggery in southern Australia. Between 29 and 35 weeks of age, gilts were examined daily for response to the back-pressure test (BPT). Those subjectively assessed as showing a moderate or high response were taken to a boar for mating. Gilts that had showed a moderate response to the BPT on their first day of mating had lower average litter size than gilts showing a high BPT response (9.05 and 9.35 piglets, respectively; P < 0.05). A quantitative assessment of sexual receptivity was made while the gilt was with the boar. Gilts that were mated while showing low sexual receptivity on the first day of mating had poorer farrowing rate (78.1 vs. 83.1%, respectively; P < 0.05), as well as lower litter size (9.03 vs. 9.35 piglets, respectively; P < 0.05) than gilts that were mated when showing high sexual receptivity. A moderate BPT response was followed by either low sexual receptivity or failure to mate on 81.4% of occasions, compared with 12.8% for a high BPT response. Since 75% of gilts that showed a moderate BPT response on the first day of mating showed a high response on the following day, it was concluded that mating should only be attempted when gilts exhibit a high response to the BPT. The mean farrowing rate and litter size for gilts at their first farrowing was 82.4% and 9.31 piglets (8.62 alive and 0.69 dead), respectively.     

Factors affecting placental traits and relationships of placental traits with neonatal behaviour in goat

The relationships between placental characteristics and litter weight, factors affecting these characteristics, and the relationship between these characteristics and neonatal behaviour of goat kids were investigated in this study. The study was carried out over three consecutive years and animal material consisted of total 152 Turkish Saanen goats and their 230 kids. The results of the study demonstrated that there were positive correlations between litter weight (LW), cotyledon number (CN), placental weight (PW) (r=0.64 and 0.76, P<0.01), but there was negative correlation between LW and cotyledon density (CD) (r=-0.42, P<0.01). CD was negatively correlated with PW (r=-0.61, P<0.01). CN and PW were influenced by the parity of doe, birth type-sex combination, buck within years and year of the study. On the other hand, parity and birth type-sex combination had no effect on PE (P>0.05), but buck within year affected placental efficiency (P<0.01). CD was only influenced by the parity of doe (P<0.01). Duration of birth (D) was not significantly related with CD, but if CD declined, it prolonged (r=-0.23, P>0.05). There were strong relationships between CD and birth-to-standing (B-St), and CD and birth-to-suckling (B-Su) (r=-0.42 and -0.51, P=0.01 and P<0.01).The results of the present study have shown similarities to the findings of the studies in sheep. Further studies are required to investigate the basis of the relationship between CD and neonatal behaviour.     

The binding of estrogen and estrogen antagonists to the estrogen receptor.

The model of the estrogen receptor as a dimer of identical, interacting subunits and data obtained by Sasson and Notides (1988, Mol. Endocrinol. 2, 307-312) were used to find the standard free energy changes that describe the binding of estradiol and 4-hydroxytamoxifen to the estrogen receptor. For the binding of estradiol or 4-hydroxytamoxifen to the estrogen receptor the data do not deviate systematically from the best fit to the model. The standard free energy change for binding of one molecule of estradiol at one site and one molecule of 4-hydroxytamoxifen at the second site of estrogen receptor indicates that 4-hydroxytamoxifen antagonizes the binding of estradiol to the estrogen receptor.     

The time of ovulation in relation to estrus duration in gilts

The objective of this study was to determine time of ovulation, monitored by transcutaneous ultrasonography, relative to the duration of estrus in gilts. We exposed 92 cyclic gilts, Camborough x Canabrid terminal line, at Day 19 of their third estrous cycle to vasectomized boars every 6 h for the detection estrus. Transcutaneous ultrasonography was performed every 6 h, starting 24 h after the onset estrus, to determine time of ovulation. Estrus duration was, on average, 52.6 h (range: 30 to 72 h), and ovulation occurred between 30 and 60 h after the onset of estrus (mean: 44 h), about 85 % of the way through the estrus period. The time of ovulation during estrus was dependent on the duration of estrus (Time of ovulation = (duration of estrus) x 0.409 + 22.7; r = 0.57, P = 0.0001). Prediction of the time of ovulation in relation to duration of estrus is important for determining the optimal time for inseminating gilts. This knowledge would contribute to an improvement in the fertilization rate and in reproductive efficiency of the breeding herd.     

Puff expression in relation to genotype]

The studies of genotype influence on puff size in salivary gland chromosomes of Drosophila virilis (stocks 9, 101, 142, 151) and D. texana (the stock 123) reveal significant differences between the species concerning the structure of puff in the 3-C-6 region at the stage of puparium formation. In reciprocal F1 hybrids the size of the puff was intermediate in comparison with parental forms having a slight maternal effect. The differences in puff size in the 5th chromosome between interspecific hybrids and the special stock of D. virilis carrying a region of D. texana 5th chromosome in heterozygous condition (inserted into D. virilis 5the chromosome by double crossing-over) were observed. The transfer of the region of the third chromosome to near centrimetric heterochromatic of the 5th chromosome by translocation resulted in the increase in the 3-B-2 puff size. However, the transposition of the 3-B1 region in the proximal direction with respect to chromocenter did not affect the puff size.     

Periovulatory hormone profiles and components of litter size in gilts with different estrogen receptor (ESR) genotypes

Estrus, endocrine changes during the periovulatory period, and components of litter size at Day 35/36 of pregnancy were studied in gilts with estrogen receptor genotype AA (AA gilts) or BB (BB gilts), in which the B allele is associated with a larger litter size. Neither estrus length nor estrous cycle length was affected by estrogen receptor genotype. No differences in periovulatory plasma LH, estrogen or progesterone profiles between the AA and BB gilts were detected. Furthermore, temporal aspects of these profiles were not different for both genotypes. Although the B allele is associated with a larger litter size, no differences in number of corpora lutea or number and percentage of vital Day 35/36 embryos were found in this study. This indicates that the difference in litter size is not due to differences in oocyte maturation, fertilization, implantation or embryonic survival, but is likely caused by a difference in fetal survival. Thus, uterine capacity might be different for both genotypes. The available uterine space per embryo seems to be the same for both genotypes, as is endometrial folding of uterine surface area. However, a difference in placental size was found. Embryos of BB gilts had significantly longer placentae than embryos of AA gilts. These results suggest a higher chance for placental insufficiency in AA gilts, leading to the expected higher fetal mortality compared with the BB gilts. The difference in placental size might have been related to a difference in the timing of embryonic mortality.     

Estradiol and progesterone receptor levels in human breast cancer in relation to cytosol and plasma estrogen level

Estradiol receptor (ER) and progesterone receptor (PR) content along with the cytosol and plasma estrone and estradiol levels in 15 premenopausal and 26 postmenopausal women with breast cancer in different clinical stages (T₁₂₃, N₀₁, M₀) were measured. ER-positive tumor frequency and the ER content tended to be higher in postmenopausal than in premenopausal patients. There was no evidence for a relationship between high cytosol estrogen levels and low receptor measurements. The estrogen concentration was higher in ER-positive tumor cytosols than in those of ER-negative tumors; the differences were significant in postmenopausal women, only, with P < 0.05 for estrone and P < 0.01 for estradiol values. Twelve pairs of tumor and normal tissue from the same breast, were also studied: seven of which contained ER-positive and five ER-negative tumors. The ER-positive tumors showed a clear trend to higher estradiol content as compared to the corresponding normal tissues. The circulating level of estradiol in postmenopausal women, was higher (P < 0.05) in ER-positive tumors than that in ER-negative tumors. Our results indicate that: (a) false negative ER assays are not likely to be due to the presence of endogenous estrogens, (b) higher amounts of estrone and estradiol are contained in ER-positive tumors than in negative ones.     

A relation between osteoclastogenesis inhibition and membrane-type estrogen receptor GPR30

Disruption of the cooperative balance between osteoblasts and osteoclasts causes various bone disorders, some of which are because of abnormal osteoclast recruitment. Osteoporosis, one of the bone disorders, is not effectively treated by currently available medicines. In addition to the development of novel drugs for palliative treatment, the exploitation of novel compounds for preventive treatment is important in an aging society. Quercetin, a major flavonoid found in many fruits and vegetables, has been expected to inhibit cancer and prevent several diseases because of its anti-inflammatory and estrogenic functions. It has been reported that quercetin has the potential to reduce bone resorption, but the mechanism by which this compound affects the differentiation of osteoclasts remains unknown. Here, using a bone marrow cell-based in vitro osteoclast differentiation system from bone marrow cells, we found that the ability of quercetin to inhibit osteoclastogenesis was related to its estrogenic activity. The inhibition was partially blocked by a specific antagonist for the nuclear receptor estrogen receptor α, but a specific antagonist of the membrane-type receptor GPR30 completely ablated this inhibition. Furthermore, quercetin suppressed the transient increase of Akt phosphorylation induced by the stimulation of macrophage colony-stimulating factor and receptor activator of NF-κB ligand with no effect on MAPK phosphorylation, suggesting exquisite crosstalk between cytokine receptor and G-protein coupled receptor signaling. These results indicate the important role of GPR30 in osteoclast differentiation and provide new insights to the development of new treatments for osteoporosis.     

TET2 is a component of the estrogen receptor complex and controls 5mC to 5hmC conversion at estrogen receptor cis-regulatory regions

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Interactions of the bovine placental lactogen and prolactin receptor genes are associated with fertility traits in cattle

Decline in fertility of high-producing dairy cattle has become a global challenge to the dairy industry. Because of low heritability and complexity, it is difficult to find genetic markers for fertility traits in cattle. Here, we report the use of an in vitro fertilization (IVF) system and candidate gene approach to test genetic associations of a single-nucleotide polymorphism (SNP) in bovine placental lactogen (bPL), and its interactions with SNPs in the prolactin receptor (PRLR) and growth hormone receptor genes with fertility traits in an IVF system. The associations suggest a possible involvement of genetic interactions between bPL and PRLR in the fertilization and embryonic development processes, and the potential for application in a marker-assisted selection program.     

Dexamethasone suppresses estrogen action at the pituitary level without modulating estrogen receptor dynamics

The administration of glucocorticoid combined with antiestrogen such as clomiphene has been shown to be effective for the induction of ovulation in patients with anovulation. The present study was undertaken to examine the effects of glucocorticoid on estrogen-induced changes in the pituitary gland. A single intraperitoneal (i.p.) administration of 10 micrograms estradiol-17 beta (E2) in ovariectomized and adrenalectomized rats resulted in a significant stimulation of pituitaries with regard to wet tissue weight and progesterone receptor content. An i.p. administration of 1 mg dexamethasone in these animals had no effects on both the values. However, the E2-induced increases in pituitary weight and progesterone receptor content were significantly inhibited by pretreatment with 1 mg of dexamethasone. The pretreatment with dexamethasone, on the other hand, had no significant effect on the dynamics of pituitary estrogen receptor induced by the injection of E2, i.e. the degree of nuclear translocation, occupancy and cytoplasmic receptor replenishment. The inhibitory effect of dexamethasone, therefore, does not seem to be mediated through estrogen receptor system in the pituitary. These results suggest that dexamethasone acts directly on the pituitary gland to suppress the action of E2, and which may be involved in the process of induction of ovulation by glucocorticoid-clomiphene treatment.     

CC chemokine receptor 5 cell-surface expression in relation to CC chemokine receptor 5 genotype and the clinical course of HIV-1 infection.

CCR5 cell-surface expression was studied in relation to CCR5 genotype and clinical course of HIV-1 infection. HIV-1 infected CCR5+/+ individuals had higher percentages of CCR5-expressing CD4+ T cells as compared with HIV-1-infected CCR532/+ individuals. For both genotypic groups, the percentages of CCR5-expressing cells were higher than for the uninfected counterparts (CCR5+/+, HIV+ 28% and HIV- 15% (p < 0.0001); CCR532/+, HIV+ 21% and HIV- 10% (p = 0.001), respectively). In HIV-1-infected individuals, high percentages of CCR5-expressing cells were associated with low CD4+ T cell numbers (p = 0.001), high viral RNA load in serum (p = 0.046), and low T cell function (p = 0.054). As compared with nonprogressors with similar CD4+ T cell numbers, individuals who did progress to AIDS had a higher percentage of CCR5-expressing CD4+ T cells (32% vs 21% (p = 0.002). Longitudinal analysis of CCR5+/+ individuals revealed slight, although not statistically significant, increases in CCR5-expressing CD4+ T cells and CD4+ T cell subsets characterized by the expression of CD45 isoforms, during the course of HIV-1 infection. Preseroconversion, the percentage of CCR5-expressing CD4+ T cells was higher in individuals who subsequently developed AIDS (28%) than in those who did not show disease progression within a similar time frame (20%; p = 0.059). Our data indicate that CCR5 expression increases with progression of disease, possibly as a consequence of continuous immune activation associated with HIV-1 infection. In turn, CCR5 expression may influence the clinical course of infection.