Mechanisms of lipid metabolism in uterine receptivity and embryo development

Author(s):  
Qianhong Ye ◽  
Xiangzhou Zeng ◽  
Shuang Cai ◽  
Shiyan Qiao ◽  
Xiangfang Zeng
2020 ◽  
Vol 26 (3) ◽  
pp. 154-166 ◽  
Author(s):  
Vanessa de Oliveira ◽  
Jennifer Schaefer ◽  
Basim Abu-Rafea ◽  
George A Vilos ◽  
Angelos G Vilos ◽  
...  

Abstract The study investigated the effect of normal and supraphysiological (resulting from gonadotropin-dependent ovarian stimulation) levels of estradiol (E2) and progesterone (P4) on mouse uterine aquaporin gene/protein (Aqp/AQP) expression on Day 1 (D1) and D4 of pregnancy. The study also examined the effect of ovarian stimulation on uterine luminal closure and uterine receptivity on D4 of pregnancy and embryo implantation on D5 and D7 of pregnancy. These analyses revealed that the expression of Aqp3, Aqp4, Aqp5 and Aqp8 is induced by E2 while the expression of Aqp1 and Aqp11 is induced by P4. Additionally, P4 inhibits E2 induction of Aqp3 and Aqp4 expression while E2 inhibits Aqp1 and Aqp11 expression. Aqp9, however, is constitutively expressed. Ovarian stimulation disrupts Aqp3, Aqp5 and Aqp8 expression on D4 and AQP1, AQP3 and AQP5 spatial expression on both D1 and D4, strikingly so in the myometrium. Interestingly, while ovarian stimulation has no overt effect on luminal closure and uterine receptivity, it reduces implantation events, likely through a disruption in myometrial activity and embryo development. The wider implication of this study is that ovarian stimulation, which results in supraphysiological levels of E2 and P4 and changes (depending on the degree of stimulation) in the E2:P4 ratio, triggers abnormal expression of uterine AQP during pregnancy, and this is associated with implantation failure. These findings lead us to recognize that abnormal expression would also occur under any pathological state (such as endometriosis) that is associated with changes in the normal E2:P4 ratio. Thus, infertility among these patients might in part be linked to abnormal uterine AQP expression.


2013 ◽  
Vol 25 (1) ◽  
pp. 149
Author(s):  
M. Schindler ◽  
M. Pendzialek ◽  
T. Plösch ◽  
J. M. Knelangen ◽  
J. Gürke ◽  
...  

The incidence of overweight and obesity has reached epidemic levels worldwide. Even more alarming is the increasing prevalence of metabolic diseases in younger children and adolescents. The rate of women with diabetes mellitus in child-bearing age is rising, too. According to the developmental origins of health and disease (DOHaD) paradigm, exposure to a hyperglycaemic environment in utero may programme physiology and metabolism permanently, with long-term consequences for offspring health. Experimental evidence indicates that programming of obesity does occur during early embryo development, a period where many women are unaware of pregnancy. To study effects of maternal diabetes mellitus on early embryo development, we induced a type I diabetes through alloxan treatment of female rabbits. In diabetic rabbits, the triglyceride and cholesterol concentrations were altered in serum and the cholesterol concentration in the uterine secretions was elevated. Lipid content of 6-day-old blastocysts was analysed after Oil Red staining and whole mount histochemistry or with Nile Red by fluorescence-activated cell sorting (FACS). Analysis by FACS revealed an approximately 2-fold increase in lipid droplets in blastocysts grown under diabetic conditions. The expression of genes important for lipid metabolism, such as fatty acid transport protein 4 (FATP4), fatty acid-binding protein 4 (FABP4), carnitine palmitoyltransferase 1 (CPT-1), and lipoprotein lipase (LPL), were determined by real-time PCR and showed distinct differences between diabetic and control blastocysts. Immunohistochemical staining of FABP4 was clearly increased in blastocysts grown under diabetic conditions and showed a cell lineage-specific distribution. Two transcription factors, peroxisome proliferator-activated receptor α (PPARα) and PPARγ, with key functions in lipid metabolism and adipogenic differentiation, were increased in blastocysts from diabetic rabbits. We show that maternal diabetes mellitus leads to alteration in lipid metabolism and to triglyceride accumulation in blastocysts. Its long-lasting consequences (e.g. for adipose cell differentiation) need attention and further investigation.


2005 ◽  
Vol 17 (9) ◽  
pp. 112
Author(s):  
J. J. Bromfield ◽  
S. A. Robertson

Optimal uterine receptivity and viability of the preimplantation embryo are key requirements for successful initiation of a pregnancy. The molecular and cellular events activated by insemination are thought to play a role in establishing an environment conducive to positive pregnancy outcomes. Previously, we have employed a blastocyst transfer model to demonstrate that lack of uterine exposure to seminal plasma at the time of conception results in fetal growth restriction and impaired postnatal development of progeny. Here we utilise a 2-cell embryo transfer technique to determine the effects of uterine seminal plasma exposure on embryo development and its subsequent effects on pregnancy outcomes at term in the mouse. Two-cell embryos were collected from donor mice and transferred into the oviduct of day 1 pseudopregnant recipient females primed either by mating with vasectomised (vas) males or vasectomised males from which the seminal vesicle glands, the major source of seminal plasma, had been surgically removed (vas+svx). At day 18 of pregnancy there was no difference in the number of total implantations, however fetal weight was reduced by approximately 5% (P < 0.05). Placental weight at day 18 was significantly increased, resulting in an increase in the fetal weight: placental weight ratio, an indicative measure of placental function. At term, progeny from pregnancies initiated in the absence of semen exhibited a 10% reduction in birth weight and remained smaller through the pre-weaning period. Fetal growth retardation was more severe when embryos were transferred at 2-cell stage than in comparable experiments where blastocysts were transferred after development in a normal donor tract. In combination, these experiments demonstrate that seminal plasma exposure at the time of conception impacts on pregnancy outcome through independent actions on both uterine receptivity and embryo development. These findings are important when considering current practises of assisted reproductive technologies, as well as having implications in pregnancy outcomes in the general population where seminal plasma signalling may be compromised.


2012 ◽  
Vol 24 (1) ◽  
pp. 155 ◽  
Author(s):  
L. O'Hara ◽  
S. Scully ◽  
V. Maillo-Sevilla ◽  
A. K. Kelly ◽  
P. Duffy ◽  
...  

Progesterone (P4) has a crucial impact on the transcriptome of the uterine endometrium and the preparation of the uterus to support implantation. The aim of this study was to investigate the effect of follicle aspiration just before ovulation on corpus luteum (CL) development, circulating P4 concentrations and the ability of the uterus to support embryo development and conceptus elongation. We tested the hypothesis that the unavoidable loss of follicular fluid and some granulosa cells during aspiration of the preovulatory follicle would compromise the development and function of the developing CL and that this would be associated with reduced P4 and a poorer uterine environment. Oestrous cycles of crossbred beef heifers were synchronized using an 8-day CIDR treatment with administration of a prostaglandin F2α analogue on the day before CIDR removal to ensure CL regression. Heifers were checked for signs of oestrus 4 times per day commencing 30 h after CIDR withdrawal and only those recorded in standing oestrus (Day 0, n = 20) were used. All heifers received a gonadotropin-releasing hormone agonist (0.01 mg buserelin) 48 h after CIDR removal to induce an LH surge. Half of the animals underwent follicle aspiration 20 h later, while the remainder underwent ovulation. Daily transrectal ultrasonography was carried out from Day 3 to 13 to record CL development. Daily blood samples were collected from Day 0 to 14 for circulating P4 concentrations. To test the ability of the uterus to support embryo development and conceptus elongation, Day 7 in vitro-produced blastocysts were transferred to the uteri of synchronised recipients (7 to 10 blastocysts per recipient). All recipients were slaughtered on Day 14 to assess embryo survival and conceptus size. CL diameter and CL area were significantly reduced in the follicle aspirated group compared with controls from Day 6 onwards (P ≤ 0.05). Similarly, at slaughter on Day 14, CL weight (4.17 ± 0.48 vs 7.05 ± 1.65 mm), diameter (19.89 ± 1.35 vs 24.64 ± 2.07 mm) and area (321.94 ± 45.01 vs 510.18 ± 69.41 mm2) were lower in aspirated heifers (P ≤ 0.05). Circulating P4 concentrations were lower at all time points from Day 3 to Day 14 but were only significantly lower from Day 12 onwards (P ≤ 0.05). Conceptus length (2.08 ± 0.29, n = 56 vs 4.55 ± 0.78 mm, n = 45) and area (2.52 ± 0.39 vs 5.61 ± 1.12 mm2) were lower (P ≤ 0.05) in heifers undergoing follicular aspiration compared with those undergoing ovulation. In conclusion, aspiration of the preovulatory dominant follicle just before expected ovulation was associated with a compromised CL in terms of size and P4 output and this, in turn, was associated with a reduced capacity of the uterus to support the initiation of conceptus elongation. Supported by Science Foundation Ireland (07/SRC/B1156).


2017 ◽  
Vol 29 (6) ◽  
pp. 1209 ◽  
Author(s):  
Shuan Zhao ◽  
Yi Wu ◽  
Hui Gao ◽  
Alexander Evans ◽  
Shen-Ming Zeng

Interferon (IFN)-stimulated gene 15 (ISG15) is one of several proteins induced by conceptus-derived Type I or II IFNs in the uterus, and is implicated as an important factor in determining uterine receptivity to embryos in ruminants. But little is known about the role the ISG15 gene or gene product plays during embryo development. In the present study, both the expression profile and function of ISG15 were investigated in early bovine embryos in vitro. ISG15 mRNA was detectable in Day 0, 2, 6 and 8 bovine embryos, but IFN-τ (IFNT) mRNA only appeared from Day 6. This means that embryonic expression of ISG15 on Days 0 and 2 was not induced by embryonic IFNT. However, ISG15 mRNA expression paralleled the expression of IFNT mRNA in Day 6 and 8 embryos. ISG15–lentivirus interference plasmid (ISG15i) was injected into 2-cell embryos to knockdown ISG15 expression. This resulted in decreases in the proportion of hatching blastocysts, the diameter of blastocysts and cell number per diameter of blastocysts compared with control embryos. In addition, ISG15i inhibited IFNT, Ets2 (E26 oncogene homolog 2) mRNA and connexion 43 protein expression in Day 8 blastocysts, whereas exogenous IFNT treatment (100 ng mL–1, from Day 4 to Day 8) improved ISG15 mRNA and connexion 43 protein expression. In conclusion, it appears that ISG15 is involved in early bovine embryo development and that it regulates IFNT expression in the blastocyst.


2019 ◽  
Vol 86 (9) ◽  
pp. 1245-1254 ◽  
Author(s):  
Sang‐Gi Jeong ◽  
Seung‐Eun Lee ◽  
Won‐Jae Kim ◽  
Yun‐Gwi Park ◽  
Jae‐Wook Yoon ◽  
...  

2019 ◽  
Vol 211 ◽  
pp. 106220
Author(s):  
Diego Fernando Dubeibe Marin ◽  
Nathalia Nogueira da Costa ◽  
Priscilla di Paula Bessa Santana ◽  
Eduardo Baia de Souza ◽  
Otavio Mitio Ohashi

2013 ◽  
Vol 25 (3) ◽  
pp. 587
Author(s):  
M. Schindler ◽  
M. Pendzialek ◽  
T. Plösch ◽  
J. M. Knelangen ◽  
J. Gürke ◽  
...  

The incidence of overweight and obesity has reached epidemic levels worldwide. Even more alarming is the increasing prevalence of metabolic diseases in younger children and adolescents. The rate of women with diabetes mellitus in child-bearing age is rising, too. According to the developmental origins of health and disease (DOHaD) paradigm, exposure to a hyperglycaemic environment in utero may programme physiology and metabolism permanently, with long-term consequences for offspring health. Experimental evidence indicates that programming of obesity does occur during early embryo development, a period where many women are unaware of pregnancy. To study effects of maternal diabetes mellitus on early embryo development, we induced a type I diabetes through alloxan treatment of female rabbits. In diabetic rabbits, the triglyceride and cholesterol concentrations were altered in serum and the cholesterol concentration in the uterine secretions was elevated. Lipid content of 6-day-old blastocysts was analysed after Oil Red staining and whole mount histochemistry or with Nile Red by fluorescence-activated cell sorting (FACS). Analysis by FACS revealed an approximately 2-fold increase in lipid droplets in blastocysts grown under diabetic conditions. The expression of genes important for lipid metabolism, such as fatty acid transport protein 4 (FATP4), fatty acid-binding protein 4 (FABP4), carnitine palmitoyltransferase 1 (CPT-1), and lipoprotein lipase (LPL), were determined by real-time PCR and showed distinct differences between diabetic and control blastocysts. Immunohistochemical staining of FABP4 was clearly increased in blastocysts grown under diabetic conditions and showed a cell lineage-specific distribution. Two transcription factors, peroxisome proliferator-activated receptor α (PPARα) and PPARγ, with key functions in lipid metabolism and adipogenic differentiation, were increased in blastocysts from diabetic rabbits. We show that maternal diabetes mellitus leads to alteration in lipid metabolism and to triglyceride accumulation in blastocysts. Its long-lasting consequences (e.g. for adipose cell differentiation) need attention and further investigation.


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