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1.
Porcine corpora lutea (CL) fail to show a luteolytic response to prostaglandin-F-2α (PGF-2α) (ie, luteolytic sensitivity [LS]) until about day 12-13 of the estrous cycle. Although little is known of the control of LS in any species, endothelin-1 (EDN1) is believed to play a role in LS control in ruminants. Therefore, we measured mRNA and protein expression and examined the cellular localization of EDN1 precursor (pre-pro EDN1, or ppEDN1), EDN-converting enzyme-1 (ECE1), and EDN receptors (A, EDNRA and B, EDNRB) in porcine CLs collected on days 4, 7, 10, 13, and 15 of the estrous cycle to look for differences between CLs displaying (days 13-15) versus those lacking (days 4-10) LS. Abundance of ppEDN1 mRNA was greatest (and significant vs all other days) on day 7 of the cycle, whereas EDN1 protein expression did not vary during the cycle and was localized exclusively to endothelial cells (EC). Abundance of ECE1 mRNA was also greatest on day 7 (vs all other days), but ECE1 protein was significantly elevated on day 10 (vs day 4) and was immunolocalized to ECs and large luteal cells (LLC). Abundance of EDNRA mRNA was also maximal on day 7 (vs all other days) of the cycle, whereas EDNRA protein expression was not significantly changed during the cycle and was observed in LLCs, ECs, and small luteal cells (SLC). On day 13, EDNRB mRNA was significantly decreased (versus day 7). Expression of EDNRB protein was decreased on day 10 (versus all other days), and on days 13-15 (vs day 4), and was primarily localized to ECs. In conclusion, the observed elevation in ECE1 protein concentrations on day 10 and the presence of EDNRA on LLC suggests a possible role for EDN1 (resulting from the actions of ECE1) acting via EDNRA in the control of LS in the pig.  相似文献   

2.
Apoptosis occurs during early development in both in vivo‐ and in vitro‐produced embryos, and is considered as one of the causes of embryonic loss. The objectives of this study were, therefore, investigating stage‐specific expression profiles of apoptosis regulatory genes in three quality groups of in vitro‐produced bovine pre‐implantation embryos; and analysing the relationship between cell number and DNA fragmentation with expressions of those genes. The relative abundance of mRNA of 9 pro‐ (Bax, caspase‐9, Bcl‐xs, P53, Caspase‐3 and Fas) and anti‐ (Bcl‐w and Mcl‐1) apoptotic genes was analysed. Differential cell staining and terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end labelling were performed to analyse the variation in cell numbers and detect apoptotic nuclei respectively. Expression of Bax and Caspase‐3 genes was significantly (p < 0.05) higher in poor quality pre‐implantation embryos as compared with that of morphologically good quality embryos of the same developmental stages. Moreover, Mcl‐1 expression was significantly higher in good quality immature oocytes than that in the poor quality group. Moreover, higher DNA fragmentation was evidenced in morphologically poor quality blastocysts. In conclusion, our study demonstrates that Bax, caspase‐3 and Mcl‐1 can be used as potential markers of embryo quality to evaluate in vitro‐produced bovine embryos. Further studies are required to investigate specific molecular signatures that can be used in evaluating in vivo‐derived embryos.  相似文献   

3.
To determine the physiological significance of tumour necrosis factor‐α (TNFα) in the regulation of luteal functions in pig, this study was conducted to identify the presence of functional TNFα receptors in porcine corpora lutea (CL) throughout the oestrous cycle and the early gestation. The CL were isolated from pigs on days 4, 6, 8, 12 or 15 of the oestrous cycle (n=3; day 0 = oestrus) and days 15, 20 or 25 of gestation (n=3; day 0 = mating). A Scatchard analysis revealed the presence of a high‐affinity binding site for TNFα in all samples (dissociation constant; 2.7 ± 0.51 to 5.8 ± 0.50 nM ). The concentration of TNFα receptors was higher on day 15 of the oestrous cycle than on days 4 and 8 of the oestrous cycle (p < 0.05). Furthermore, TNFα receptor concentrations in the CL on days 15, 20 and 25 of gestation were significantly lower than on day 15 of the oestrous cycle (p < 0.05). On day 9 of the oestrous cycle, exposure of cultured luteal cells to 0.06–60 nM TNFα stimulated prostaglandin (PG) F2α and PGE2 secretion in a dose‐dependent manner (p < 0.05). These results indicate that functional TNFα receptors are present in the porcine CL throughout the oestrous cycle and early gestation, and suggest that TNFα plays one or more physiological roles in regulating CL function throughout the oestrous cycle and the early gestation period. In addition, TNFα receptor concentration in the CL of the late luteal stage (day 15) of the oestrous cycle was higher than on the respective day in the early pregnant pig, suggesting that TNFα plays a role in accomplishing luteolysis in the porcine CL.  相似文献   

4.
The objective of this study was to document the expression and localization of angiopoietin (ANGPT) family members comprising of angiopoietin (ANGPT1 and ANGPT2), and their receptors (Tie1 and Tie2) in buffalo corpus luteum (CL) obtained from different stages of the oestrous cycle, and the modulatory role of ANGPT1 and ANGPT2 alone or in combinations on progesterone (P4) secretion and mRNA expression of phosphotidylinositide‐3kinase‐protein kinase B (PI3K‐AKT), phosphoinositide‐dependent kinase (PDK), protein kinase B (AKT), Bcl2 associated death promoter (BAD), caspase 3 and von willebrand factor (vWF) in luteal cells obtained from midluteal phase (MLP) of oestrous cycle in buffalo. Real‐time RT‐PCR (qPCR), Western blot and immunohistochemistry were applied to investigate mRNA expression, protein expression and localization of examined factors whereas, the P4 secretion was assessed by RIA. The mRNA and protein expression of ANGPT1 and Tie2 was maximum (p < .05) in mid luteal phase (MLP) of oestrous cycle. The ANGPT2 mRNA and protein expression was maximum (p < .05) in early luteal phase, decreased in MLP and again increased in late luteal phase of oestrous cycle. ANGPT family members were localized in luteal cells and endothelial cells with a stage specific immunoreactivity. P4 secretion was highest (p < .05) with 100 ng/ml at 72 hr when luteal cells were treated with either protein alone. The mRNA expression of PDK, AKT and vWF was highest (p < .05) and BAD along with caspase 3 were lowest (p < .05) at 100 ng/ml at 72 hr of incubation period, when cultured luteal cells were treated with either protein alone or in combination. To conclude, our study explores the steroidogenic potential of angiopoietins to promote P4 secretion, luteal cell survival and angiogenesis through an autocrine and paracrine actions in buffalo CL.  相似文献   

5.
Porcine corpora lutea (CL) fail to show a luteolytic response to prostaglandin-F-2α (PGF-2α) (ie, luteolytic sensitivity, or LS) until ∼day 13 of the estrous cycle. In view of the importance of protein kinase C (PRKC) in PGF-2α signal transduction, it was hypothesized that limiting levels of 1 or more PRKC isoforms may explain the lack of LS before day 13. This hypothesis was tested by examining expression of mRNA and protein, and the cellular localization patterns of the 11 PRKC isoforms throughout the porcine estrous cycle, to determine whether PRKC expression correlates with and thus may be associated with the control of the acquisition of LS in the pig. The expression patterns show that for most PRKC isoforms (ie, PRKC alpha, beta 1, beta 2, delta, epsilon, theta, iota, and zeta), mRNA was maximally expressed on day 7 or day 10 (protein kinase D1 only) of the cycle, whereas PRKCs gamma, eta, and lambda were unchanged. At the protein level, only PRKC epsilon (PRKCE) significantly changed during the estrous cycle and was elevated on day 13 (versus days 4, 7, and 15; P < 0.05). By immunofluoresence, most PRKC isoforms, including PRKCE, were localized to steroidogenic large luteal cells (LLC) and small (nonendothelial cell) luteal cell subtypes (SLC). In conclusion, since the increase in PRKCE protein expression (day 13) occurred coincidentally with the onset of LS (≥day 12), these results support a potential role for PRKCE in control of the acquisition of LS in the pig.  相似文献   

6.
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7.
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8.
The fate of the corpus luteum, a transient endocrine gland formed and degraded during an oestrous cycle, is decided by various physiological factors, such as luteinizing hormone (LH). As a stimulator of progesterone, LH is known to maintain corpus luteum functional and structural integrity by inhibiting apoptosis, a programmed cell death. Therefore, we aim to investigate its action during the mid-luteal phase hypothesized that LH suppresses the death mechanism of bovine luteal steroidogenic cells (LSC) by analysing the expression of proteins involved. Cultured bovine LSC obtained from corpus luteum were treated for 24 hr with recombinant TNF and IFNG in the presence or absence of LH. The result showed that LH proved to have a protective effect by increased cell viability (p < .05) and prevented DNA fragmentation (p < .05), as demonstrated by the WST-1 colorimetric assay and TUNEL assay. Expression analysis of mRNA and protein levels showed that LH altered the expression of BCL2 (p < .05), CASP3 (p < .05), FAS (p < .05), and BAX (p < .05) to support cell survival. In conclusion, our study suggests that LH prolongs the corpus luteum life span through the anti-apoptotic mechanism by increasing cell viability and suppressing apoptosis-related genes and protein expression.  相似文献   

9.
Prostaglandin F2α (PGF2α) is a main luteolytic factor in vivo; however, its direct luteolytic influence on steroidogenic cells of bovine corpus luteum (CL) is controversial and not fully understood. The aim of the study was to clarify PGF2α action on bovine CL in different in vivo and in vitro conditions and to examine whether the contact among all main types of CL cells is necessary for luteolytic PGF2α action. In experiment 1, the bovine CL (day 15 of the oestrous cycle) was perfused using in vivo microdialysis system with dinoprost (an analogue of PGF2α) for 0.5 h. Dinoprost caused a short‐time increase in progesterone (P4), whose concentration decreased thereafter (at 6‐, 10‐, 12‐ and 24‐h after treatment). In experiment 2, the direct effect of PGF2α on P4 accumulation in CL steroidogenic cells cultured in monolayer (day 15 of the cycle) was determined. PGF2α after 24 h of incubation increased P4 accumulation in steroidogenic CL cells. In experiment 3 steroidogenic, endothelial CL and immune cells (day 15 of the cycle) were incubated with PGF2α in cocultures for 24 h in glass tubes and the levels of P4, stable metabolites of nitric oxide (NO) and leukotriene (LT) C4 were determined. Although PGF2α treatment increased P4 secretion in homogeneous steroidogenic CL cell culture, the decrease in P4 secretion in cocultures of all types of CL cells was observed. The secretion of NO and LTC4 increased after the treatment of PGF2α both in pure cultures of CL cells and in cocultures. The interactions between endothelial and immune cells with steroidogenic CL cells are needed for luteolytic PGF2α action within the bovine CL. Our results indicate that the cell coculture model, including the main types of CL cells, is the most approximate to study PGF2α role in vitro.  相似文献   

10.
The aims of this study were to study the effects of fasting on progesterone (P4) production in the pig and to verify whether fasting influences luteal expression of PGF(2alpha) receptor (FPr) and prostaglandin secretion. Superovulated prepubertal gilts were used; half of them were fasted for 72h starting on day 2 (F2) or 9 (F9) of the induced estrous cycle, respectively, while two groups (C2 and C9) served as respective controls. Plasma P4 and PGFM concentrations were determined by RIA while FPr mRNA expression in CLs collected at the end of fasting period was measured by real-time PCR. In experiment 1, plasma P4 concentrations in fasted gilts were significantly (P<0.01) higher than in controls starting from day 3 (F2; n=6) and 10 (F9; n=6). FPr mRNA expression was similar in F2 and C2 (n=6) CLs while it was significantly (P<0.05) higher in F9 than in C9 (n=6) CLs. In experiment 2, cloprostenol administered on day 12 significantly (P<0.05) increased FPr mRNA expression in CLs from both F9 (n=6) and C9 (n=6) gilts. At the time of cloprostenol injection PGFM levels were significantly higher (P<0.05) in the fasted group and cloprostenol-induced luteolysis in fasted but not in normally fed gilts. Results from this study indicate that fasting in prepubertal gilts induced to ovulate stimulates luteal P4 and PGFM production as well as FPr mRNA expression, thus increasing luteolytic susceptibility.  相似文献   

11.
As the exact role for exogenous oestrogen in spermatogenesis is not fully understood, the aim of this study was to investigate the effect of estradiol benzoate (EB) exposure to male mice on their spermatogenesis and fertility. Sixty male mice aged 4 weeks were randomly divided into three groups, including a control group and two treatment groups. The mice of the control group were injected with 250 μl paraffin oil only by every other day subcutaneous injection for 4 weeks. Meantime, the mice of the treatment groups were injected with EB at the concentration of 5 or 10 mg/kg, respectively. Results showed that EB slowed down the body weight gains and generated testicular atrophy with spermatogenesis disorder compared with that of the control mice, and consequently induced their infertility. Moreover, the number of TUNEL‐positive cells in the testis of EB‐treated mice was significantly increased with the EB concentration rise. In comparison with controls, the mRNA expression level of pro‐apoptosis factors (Fas, TNF, Cytochrome C, Apaf1, Chop, Caspase‐3, Caspase‐8, Caspase‐9 and Caspase‐12) and key genes in oestrogen receptor (ER) signalling pathway (ER α, ER β, Erk1/2, Hsp90 and DAX‐1) were upregulated in the testes of the treatment groups. Furthermore, Western blotting results proved the protein expression level of Fas, TNF, Cytochrome C, Chop, Caspase‐3, cleaved Caspase‐3, Caspase‐9, Erk1/2 and Hsp90 were upregulated, and the phosphorylation level of Erk1/2 was also increased. These results indicate that EB may impair spermatogenesis through influencing the apoptosis and ER signalling pathway.  相似文献   

12.
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13.
The aim of the present study was to elucidate the fundamental mechanism of bovine oviduct epithelial cell (BOEC) co‐culture on developmental capacity of bovine in vitro oocyte maturation/in vitro fertilization (IVM/IVF) embryos. We examined the effects of astaxanthin against nitric oxide‐induced oxidative stress on cell viability by MTT assay, lipid peroxidation (LPO) by using thiobarbituric acid (TBA) reaction for malondialdehyde (MDA) and the expression of antioxidant genes (CuZnSOD, MnSOD and Catalase) or apoptosis genes (Bcl‐2, Caspase‐3 and Bax) by RT‐PCR in BOEC. We also evaluated the developmental rates of bovine IVM/IVF embryos co‐cultured with BOEC pre‐treated with astaxanthin (500 μm ) in the presence or absence of sodium nitroprusside (SNP, 1000 μm ) for 24 h. Cell viability in BOEC treated with SNP (50–2000 μm ) lowered, while astaxanthin addition (50–500 μm ) increased it in a dose‐dependent manner. Cell viability in astaxanthin plus SNP (1000 μm ) gradually recovered according to the increase in astaxanthin additions (100–500 mm ). The LPO in astaxanthin group (50–500 μM) gradually decreased in a dose dependent manner and among SNP or astaxanthin plus SNP group, SNP alone and astaxanthin (50 μM) plus SNP shown a significant increase than other groups (p < 0.05). Expression of apoptosis or antioxidant genes was detected by RT‐PCR. Bcl‐2 and antioxidant genes were detected in astaxanthin or astaxanthin plus SNP group, and Caspase‐3 and Bax genes were only found in SNP group. When bovine IVM/IVF embryos were cultured for 6–7 days under co‐culture system such as BOEC treated with astaxanthin in the presence or absence of SNP, the developmental ability to blastocysts in 500 μm astaxanthin group was the highest of all groups. These results suggest that astaxanthin has a antioxidative effect on cell viability and LPO of BOEC, and development of bovine IVM/IVF embryos due to the induction of antioxidant genes and suppression of apoptosis genes.  相似文献   

14.
The non‐invasive type of implantation in the pig is characterized by the maintenance of a thick glycocalyx coating on the uterine epithelial surface microvilli. Present study investigated the alteration in the sialomucin complex (Muc4) expression during the oestrous cycle and early pregnancy in the pig. Endometrial tissue samples were immunostained with the primary antibody to the Muc4 transmembrane subunit ASGP‐2. Muc4 immunostaining increased in the surface and glandular epithelia between days 5 and 10 of oestrous cycle. Immunostaining continued to increase on day 12 with the greatest intensity of uterine Muc4 immunostaining detected on day 15 of the oestrous cycle and early pregnancy. Endometrial Muc4 expression in cyclic gilts decreased dramatically during early proestrous but continued to remain abundant in the surface and glandular epithelium of pregnant gilts during the period of conceptus attachment to the uterine surface.  相似文献   

15.
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16.
The aim of this study was to determine leukotrienes (LTs) functions in the bovine corpus luteum (BCL) during the oestrous cycle. In steroidogenic CL cells we examined the effect of luteotropic [LH, prostaglandin E2 (PGE2)] and luteolytic (PGF2α, cytokines) factors on: the levels of LTB4 and C4, the expression of 5‐lipoxygenase (LO), LT receptors type I (LTR‐I) and LTR‐II, and the effects of LTB4 and C4 stimulations on the levels of progesterone (P4), PGE2, F2α and nitric oxide (NO) metabolites. Both luteolytic and luteotropic factors stimulated 5‐LO expression on days 2–4 and 17–19 of the cycle. Leukotriene receptors type I expression increased after PGE2 and tumour necrosis factor α with interferon γ (TNF/IFN) stimulation on days 2–4 of the cycle. Leukotriene receptor type II expression increased after PGE2α and TNF/IFN stimulation on days 2–4 and 17–19 of the cycle, and LTR‐II expression on days 8–10 of the cycle was unchanged after cell stimulation with any factor. Leukotriene B4 level increased after BSC incubation with luteotropic factors during all examined days of the cycle and after cytokine stimulation at early‐ and mid‐luteal stages, whereas luteolytic factors stimulated LTC4 secretion over the entire cycle. Leukotriene B4 stimulated P4 secretion at the mid‐luteal stage and stimulated NO secretion during all examined phases. Leukotriene B4 stimulated PGE2 secretion at the early‐ and mid‐luteal stage. Leukotriene C4 inhibited P4 secretion at the mid‐ and regressing‐luteal stage, stimulated NO (entire cycle) and PGF2α at mid‐ and regressing‐luteal phases. Leukotrienes modulate steroidogenic cells functions, depending on the stage of the cycle. Leukotriene B4 plays a luteotropic role stimulating P4 and PGE2 secretions; LTC4 stimulates the secretion of luteolytic factors and enhances the luteolytic cascade within BCL.  相似文献   

17.
The Wnt/β‐catenin pathway is a conserved signalling pathway that regulates gene expression and controls diverse developmental processes such as cell fate specification, cell proliferation and cell differentiation. To our knowledge, the potential role of this pathway in the adult ovary has been poorly addressed. To this end, we investigated the expression pattern of Frizzled 2 in the mouse ovary during oestrous cycle by real‐time Q‐PCR, in situ hybridization, Western blotting and immunohistochemistry. In this study, we used uterine wet weight and H3.2 mRNA level as two markers for classification of mouse oestrous cycle. We found that both uterine wet weight and H3.2 mRNA are the highest in the proestrus and decrease from oestrus to diestrus. During oestrous cycle, Frizzled 2 mRNA and protein exhibited the highest level in the proestrus stage and rapidly reduced from oestrus to diestrus. In situ hybridization results showed that the positive signals for Frizzled 2 are highly detected in the oocyte and stroma in proestrus stage, while moderate or weak Frizzled 2 mRNAs are localized in the oocyte, granulosa cells, stroma and corpus luteum from oestrus to diestrus. The localization pattern of Frizzled 2 protein is mostly consistent with its mRNA, but stronger Frizzled 2 proteins are present in the granulosa cells and membrane of oocyte in oestrous cycle. Our data suggest that Frizzled 2 may be involved in regulating follicle growth, oocyte maturation and luteinization during oestrous cycle.  相似文献   

18.
Follicular estradiol triggers luteolysis in cattle. Therefore, the control of follicle growth and steroidogenesis is expected to modulate luteal function and might be used as an anti‐luteolytic strategy to improve embryo survival. Objectives were to evaluate follicular dynamics, plasma concentrations of estradiol and luteal lifespan in Bos indicus and crossbred cows subjected to sequential follicular aspirations. From D13 to D25 of a synchronized cycle (ovulation = D1), Nelore or crossbred, non‐pregnant and non‐lactating cows were submitted to daily ultrasound‐guided aspiration of follicles >6 mm (n = 10) or to sham aspirations (n = 8). Diameter of the largest follicle on the day of luteolysis (7.4 ± 1.0 vs 9.7 ± 1.0 mm; mean ± SEM), number of days in which follicles >6 mm were present (2.3 ± 0.4 vs 4.6 ± 0.5 days) and daily mean diameter of the largest follicle between D15 and D19 (6.4 ± 0.2 vs 8.5 ± 0.3 mm) were smaller (p < 0.01) in the aspirated group compared with the control group, respectively. Aspiration tended to reduce (p < 0.10) plasma estradiol concentrations between D18 and D20 (2.95 ± 0.54 vs 4.30 ± 0.55 pg/ml). The luteal lifespan was similar (p > 0.10) between the groups (19.6 ± 0.4 days), whereas the oestrous cycle was longer (p < 0.01) in the aspirated group (31.4 ± 1.2 vs 21.2 ± 1.3 days). Hyperechogenic structures were present at the sites of aspiration and were associated with increase in concentration of progesterone between luteolysis and oestrus. It is concluded that follicular aspiration extended the oestrous cycle and decreased the average follicular diameter on the peri‐luteolysis period but failed to delay luteolysis.  相似文献   

19.
Apoptosis of granulosa cells affects follicular atresia and reproduction and is regulated by miRNAs and the expression of certain genes. For the present study, we investigated the regulatory relationship between microRNA‐222 (miR‐222) and THBS1 in porcine follicular granulosa cells (pGCs) and its effects on apoptosis to provide empirical data for developing methods to improve pig fecundity. Results revealed that miR‐222 promotes the proliferation of pGCs. MiRNA mimics and luciferase reporter assays revealed that miR‐222 functions as an anti‐apoptotic factor in pGCs. MiR‐222 mimics in pGCs result in the upregulation of the anti‐apoptotic BCL‐2 gene, down‐regulation of the proapoptotic caspase‐3 gene, and inhibition of apoptosis. MiR‐222 inhibitors reduced BCL‐2 and had no significant effect on caspase‐3. MiR‐222 mimics promoted estrogen levels. Inhibition of THBS1 inhibited pGC apoptosis. Transfection of THBS1‐siRNA reduced the proapoptotic BAX gene. MiR‐222 can directly target the 3′‐untranslated region of the THBS1 gene. MiR‐222 mimics suppressed THBS1 mRNA and proteins, but these were upregulated by the miR‐222 inhibitor. Transfection of THBS1‐siRNA resulted in the inhibition of the miR‐222 inhibitor, which suggests that miR‐222 inhibits pGC apoptosis by targeting THBS1. These findings suggest that miR‐222 and THBS1 play important roles in follicular atresia, ovarian development, and female reproduction.  相似文献   

20.
This study examined the effects of O2 concentration (5% vs 20%) during in vitro maturation (IVM), fertilization (IVF) and culture (IVC) or supplementation of IVM and IVC media with cysteamine (50 and 100 μm , respectively; IVM, IVF and IVC carried out in 20% O2), on blastocyst rate and relative mRNA abundance of some apoptosis‐related genes measured by real‐time qPCR in immature and in vitro‐matured buffalo oocytes and in embryos at 2‐, 4‐, 8‐ to 16‐cell, morula and blastocyst stages. The blastocyst rate was significantly higher (p < 0.05) while the percentage of TUNEL‐positive cells was significantly lower (p < 0.05) under 5% O2 than that under 20% O2. The mRNA expression of anti‐apoptotic genes BCL‐2 and MCL‐1 was significantly higher (p < 0.05) and that of pro‐apoptotic genes BAX and BID was lower (p < 0.05) under 5% O2 than that under 20% O2 concentration at many embryonic stages. Following cysteamine supplementation, the blastocyst rate and the relative mRNA abundance of BCL‐XL and MCL‐1 was significantly higher (p < 0.05) and that of BAX but not BID was lower (p < 0.05) at many stages of embryonic development, although it did not affect the percentage of TUNEL positive cells in the blastocysts significantly. The mRNA expression pattern of these genes during embryonic development was different in 5% vs 20% O2 groups and in cysteamine supplemented vs controls. At the 8‐ to 16‐cell stage, where developmental block occurs in buffalo, the relative mRNA abundance of BCL‐2 and MCL‐1 was highest under 5% O2 concentration and that of BAX and BID was highest (p < 0.05) under 20% O2 concentration. These results suggest that one of the mechanisms through which beneficial effects of low O2 concentration and cysteamine supplementation are mediated during in vitro embryo production is through an increase in the expression of anti‐apoptotic and a decrease in the expression of pro‐apoptotic genes.  相似文献   

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