Homozygous mutation of foxh1 arrests oogenesis causing infertility in female Nile tilapia†

2019 ◽  
Vol 102 (3) ◽  
pp. 758-769
Author(s):  
Wenjing Tao ◽  
Hongjuan Shi ◽  
Jing Yang ◽  
Hamidou Diakite ◽  
Thomas D Kocher ◽  
...  
Keyword(s):  
Phase Iii ◽  
Follicle Cells ◽  
Homozygous Mutation ◽  
Serum Estradiol ◽  
Oocyte Growth ◽  
Expression Of Genes ◽  
Estrogen Production ◽  
Estrogen Synthesis ◽  
Smad Protein ◽  
Estradiol 17Β

Abstract Foxh1, a member of fox gene family, was first characterized as a transcriptional partner in the formation of the Smad protein complex. Recent studies have shown foxh1 is highly expressed in the cytoplasm of oocytes in both tilapia and mouse. However, its function in oogenesis remains unexplored. In the present study, foxh1−/− tilapia was created by CRISPR/Cas9. At 180 dah (days after hatching), the foxh1−/− XX fish showed oogenesis arrest and a significantly lower GSI. The transition of oocytes from phase II to phase III and follicle cells from one to two layers was blocked, resulting in infertility of the mutant. Transcriptomic analysis revealed that expression of genes involved in estrogen synthesis and oocyte growth were altered in the foxh1−/− ovaries. Loss of foxh1 resulted in significantly decreased Cyp19a1a and increased Cyp11b2 expression, consistent with significantly lower concentrations of serum estradiol-17β (E2) and higher concentrations of 11-ketotestosterone (11-KT). Moreover, administration of E2 rescued the phenotypes of foxh1−/− XX fish, as indicated by the appearance of phase III and IV oocytes and absence of Cyp11b2 expression. Taken together, these results suggest that foxh1 functions in the oocytes to regulate oogenesis by promoting cyp19a1a expression, and therefore estrogen production. Disruption of foxh1 may block the estrogen synthesis and oocyte growth, leading to the arrest of oogenesis and thus infertility in tilapia.

scholarly journals Antagonistic Roles of Dmrt1 and Foxl2 in Sex Differentiation via Estrogen Production in Tilapia as Demonstrated by TALENs

Endocrinology ◽  
2013 ◽  
Vol 154 (12) ◽  
pp. 4814-4825 ◽  
Author(s):  
Ming-Hui Li ◽  
Hui-Hui Yang ◽  
Meng-Ru Li ◽  
Yun-Lv Sun ◽  
Xiao-Long Jiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nile Tilapia ◽  
High Efficiency ◽  
Sex Differentiation ◽  
Sex Reversal ◽  
Serum Estradiol ◽  
Transcription Activator ◽  
Important Species ◽  
Estrogen Production ◽  
Estradiol 17Β

Transcription activator-like effector nucleases (TALENs) are a powerful approach for targeted genome editing and have been proved to be effective in several organisms. In this study, we reported that TALENs can induce somatic mutations in Nile tilapia, an important species for worldwide aquaculture, with reliably high efficiency. Six pairs of TALENs were constructed to target genes related to sex differentiation, including dmrt1, foxl2, cyp19a1a, gsdf, igf3, and nrob1b, and all resulted in indel mutations with maximum efficiencies of up to 81% at the targeted loci. Effects of dmrt1 and foxl2 mutation on gonadal phenotype, sex differentiation, and related gene expression were analyzed by histology, immunohistochemistry, and real-time PCR. In Dmrt1-deficient testes, phenotypes of significant testicular regression, including deformed efferent ducts, degenerated spermatogonia or even a complete loss of germ cells, and proliferation of steroidogenic cells, were observed. In addition, disruption of Dmrt1 in XY fish resulted in increased foxl2 and cyp19a1a expression and serum estradiol-17β and 11-ketotestosterone levels. On the contrary, deficiency of Foxl2 in XX fish exhibited varying degrees of oocyte degeneration and significantly decreased aromatase gene expression and serum estradiol-17β levels. Some Foxl2-deficient fish even exhibited complete sex reversal with high expression of Dmrt1 and Cyp11b2. Furthermore, disruption of Cyp19a1a in XX fish led to partial sex reversal with Dmrt1 and Cyp11b2 expression. Taken together, our data demonstrated that TALENs are an effective tool for targeted gene editing in tilapia genome. Foxl2 and Dmrt1 play antagonistic roles in sex differentiation in Nile tilapia via regulating cyp19a1a expression and estrogen production.

scholarly journals Effects of coated and noncoated steroidal implants on growth performance, carcass characteristics, and serum estradiol-17β concentrations of finishing Holstein steers

2020 ◽  
Vol 4 (4) ◽  
Author(s):  
Pedro H V Carvalho ◽  
Mariana F Westphalen ◽  
Jonathan A Campbell ◽  
Tara L Felix
Keyword(s):  
Growth Performance ◽  
Animal Health ◽  
Average Daily Gain ◽  
Carcass Characteristics ◽  
Feed Ratio ◽  
Serum Estradiol ◽  
Trenbolone Acetate ◽  
Coated Implant ◽  
Daily Gain ◽  
Estradiol 17Β

Abstract The objectives of the study were to determine the effect of coated or noncoated hormone implants on growth performance, carcass characteristics, and serum estradiol-17β (E2) concentrations of Holstein steers fed a grain-based diet for 112 d. Seventy-nine Holstein steers [average initial body weight (BW) = 452 ± 5.5 kg] were stratified by BW and allotted to one of two treatments: 1) Holstein steers implanted with a coated implant containing 200 mg of trenbolone acetate (TBA) and 40 mg E2 (Revalor-XS (Merck Animal Health; Summit, NJ)] on day 0 (XS) or 2) Holstein steers implanted two times (days 0 and 56) with a noncoated implant containing 80 mg of TBA and 16 mg of E2 [(2IS) Revalor-IS (Merck Animal Health)]. Data were analyzed using the MIXED procedure of SAS (SAS Inst. Inc., Cary, NC). There was no effect (P ≥ 0.71) of implant strategy on initial, middle, and final BW. No effect (P ≥ 0.12) of implant strategy was observed on average daily gain, dry matter intake, or gain-to-feed ratio. There were no effects (P ≥ 0.11) of implant strategy on carcass characteristics. There was an implant × day interaction (P < 0.01) for the circulation of serum E2 concentrations. Serum E2 concentration increased similarly 14 d after Holstein steers were implanted, regardless of implant strategy. At 28 d, after steers were implanted, steers in the XS group had less serum E2 concentration than Holstein steers in the 2IS group. However, at 56 d after the first implantation, both groups, once again, had similar serum E2 concentrations and E2 concentrations were less on day 56 than day 28 for both strategies. Holstein steers implanted with 2IS had greater serum E2 concentration on day 70 and E2 concentrations remained greater than serum E2 of Holstein steers implanted XS for the duration of the trial (day 112). In summary, there was no effect of coated or two doses of noncoated implant on growth performance or carcass characteristics of Holstein steers.

scholarly journals Efforts by Industry Toward Standardization of Serum Estradiol-17β Measurements

1998 ◽  
Vol 44 (3) ◽  
pp. 671-674 ◽  
Author(s):  
Linda M Thienpont ◽  
André P De Leenheer
Keyword(s):  
Serum Estradiol ◽  
Estradiol 17Β

Aromatase activity in the mare ovary during estrous cycle. Measurement of endogenous steroids and of their in vitro inhibitory effect

1993 ◽  
Vol 129 (6) ◽  
pp. 536-542 ◽  
Author(s):  
Hakima Amri ◽  
Pierre Silberzahn ◽  
Ihsan Al-Timimi ◽  
Jean-Luc Gaillard
Keyword(s):  
Follicular Fluid ◽  
Luteal Phase ◽  
Physiological Role ◽  
Inhibitory Effect ◽  
Aromatase Activity ◽  
Estrogen Production ◽  
Estrogen Synthesis ◽  
Luteal Tissue ◽  
Endogenous Steroids

This present study was undertaken to clarify estrogen synthesis in the mare ovary. First of all, an evaluation of endogenous steroid contents was carried out in the follicular fluid and in the luteal tissue at different stages of the luteal phase. Radioimmunoassays were performed after separation and purification of each hormone by chromatography. High amounts of conjugated (0.9 mg/l) and unconjugated (4 mg/l) estradiol-17β were found in the follicular fluid of the large follicules (50 mm). These concentrations of estrogens decreased drasticaly in the luteal tissue, and only low levels of circulating estrogens are found during the luteal phase. On the other hand, a high aromatization ability has been evidenced in the cyclic corpus luteum in vitro. In an attempt to clarify the regulation of estrogen synthesis, we have tested the inhibitory effect of several endogenous steroids on equine ovarian aromatase activity. 5α-Dihydrotestosterone appeared to be the most potent competitive inhibitor (Ki= 181 nmol/l) of aromatase activity, while the addition of a 3-sulfate group induced a slump in the inhibitory potency of estrone (Ki= 397 nmol/l vs 2206 nmol/l) and dehydroepiandrosterone (Ki = 291 nmol/l vs 6157 nmol/l). The physiological role of these conjugated steroids has not been known until now; we suggest that they would play a role in protecting aromatase from inhibition, in vivo. The high amounts of progesterone found in the luteal tissue (1.3 g/kg of proteins) might play a role in the regulation of estrogen production either by suppressing the induction of aromatase synthesis or by inhibiting the activity of the enzyme complex.

scholarly journals 3,5-T2 alters murine genes relevant for xenobiotic, steroid, and thyroid hormone metabolism

2016 ◽  
Vol 56 (4) ◽  
pp. 311-323 ◽  
Author(s):  
Julika Lietzow ◽  
Janine Golchert ◽  
Georg Homuth ◽  
Uwe Völker ◽  
Wenke Jonas ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Phase Iii ◽  
Whole Body ◽  
High Dose ◽  
Thyroid Hormone Metabolism ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Novel Target

The endogenous thyroid hormone (TH) metabolite 3,5-diiodo-l-thyronine (3,5-T2) acts as a metabolically active substance affecting whole-body energy metabolism and hepatic lipid handling in a desirable manner. Considering possible adverse effects regarding thyromimetic action of 3,5-T2 treatment in rodents, the current literature remains largely controversial. To obtain further insights into molecular mechanisms and to identify novel target genes of 3,5-T2 in liver, we performed a microarray-based liver tissue transcriptome analysis of male lean and diet-induced obese euthyroid mice treated for 4 weeks with a dose of 2.5 µg/g bw 3,5-T2. Our results revealed that 3,5-T2 modulates the expression of genes encoding Phase I and Phase II enzymes as well as Phase III transporters, which play central roles in metabolism and detoxification of xenobiotics. Additionally, 3,5-T2 changes the expression of TH responsive genes, suggesting a thyromimetic action of 3,5-T2 in mouse liver. Interestingly, 3,5-T2 in obese but not in lean mice influences the expression of genes relevant for cholesterol and steroid biosynthesis, suggesting a novel role of 3,5-T2 in steroid metabolism of obese mice. We concluded that treatment with 3,5-T2 in lean and diet-induced obese male mice alters the expression of genes encoding hepatic xenobiotic-metabolizing enzymes that play a substantial role in catabolism and inactivation of xenobiotics and TH and are also involved in hepatic steroid and lipid metabolism. The administration of this high dose of 3,5-T2 might exert adverse hepatic effects. Accordingly, the conceivable use of 3,5-T2 as pharmacological hypolipidemic agent should be considered with caution.

Hachimijiogan Changes Serum Hormonal Circumstance and Improves Spermatogenesis in Oligozoospermic Men

1986 ◽  
Vol 14 (01n02) ◽  
pp. 37-45 ◽  
Author(s):  
S. Usuki
Keyword(s):  
Sperm Motility ◽  
Moderate Increase ◽  
Serum Estradiol ◽  
Remarkable Increase ◽  
Testosterone Levels ◽  
Fertility Index ◽  
Significant Change ◽  
Estradiol 17Β

28 men with oligozoospermia and 7 with azoospermia received 7.5 g of Hachimijiogan, daily for 8 to 28 weeks. Examinations of semen in oligozoospermic men after treatment revealed a remarkable increase in number (78%) and moderate increase in sperm motility (53%) and in volume (56%), and fertility index was also remarkably improved, whereas no improvement was found in azoospermic men. Furthermore, serum estradiol-17β level was significantly increased (P<0.005) after treatment, while LH, FSH, prolactin and testosterone levels in sera showed no significant change. These results suggest that Hachimijiogan increases serum estradiol-17 β levels and improves spermatogenesis in oligozoospermic men.

Regulations of gonadotropin secretion by circulating inhibin, estradiol, and progesterone in cyclic hamsters

1999 ◽  
Vol 277 (5) ◽  
pp. E876-E882 ◽  
Author(s):  
Hisashi Kishi ◽  
Mariko Itoh ◽  
Ken-Ichi Ohshima ◽  
Ming-Wei Wang ◽  
Gen Watanabe ◽  
...  
Keyword(s):  
Estrous Cycle ◽  
Follicle Stimulating Hormone ◽  
Gonadal Hormones ◽  
Serum Estradiol ◽  
Elevated Plasma ◽  
Gonadotropin Secretion ◽  
Physiological Importance ◽  
Drastic Increase ◽  
Lh Secretion ◽  
Estradiol 17Β

The physiological importance of gonadal hormones in feedback control of gonadotropin secretion during the estrous cycle in golden hamsters was investigated with immunoneutralization methods. Anti-inhibin serum (inhibin-AS) treatment always induced a drastic increase in follicle-stimulating hormone (FSH) secretion and occasionally raised luteinizing hormone (LH) secretion. Anti-estradiol-17β serum (estradiol-AS) treatment increased LH secretion typically. Although estradiol-AS elevated FSH secretion occasionally, the elevation was much less than that by inhibin-AS. Plasma FSH reached ovariectomized levels by a synergistic effect of both antisera. Elevated plasma LH with both antisera was much less pronounced than in ovariectomized animals. Plasma LH increased dramatically to the levels in the ovariectomized group when antibody against progesterone (progesterone-AB) was given together with inhibin-AS and estradiol-AS, although progesterone-monoclonal antibody alone did not alter plasma gonadotropin levels. These results indicate that in hamsters FSH secretion is mainly regulated by inhibin and LH secretion is regulated by estradiol-17β and progesterone during the estrous cycle.

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