Melatonin Receptor 1A Gene Research Articles

Genotyping of rams based on melatonin receptor 1A gene polymorphisms: a tool in sire selection?

Context Several polymorphisms in the melatonin receptor 1A gene (MTNR1A ) have been related to reproductive performance in ovine. Aims To investigate the effect of the Rsa I and Mnl I polymorphisms on ram seminal quality. Methods Eighteen Rasa Aragonesa rams were genotyped for the Rsa I (C/C, C/T, T/T) and Mnl I (G/G, G/A, A/A) allelic variants of the MTNR1A gene. Individual ejaculates were analysed once a month throughout the whole year. Sperm motility, morphology, membrane integrity, levels of reactive oxygen species (ROS), phosphatidylserine (PS) inversion, DNA fragmentation and capacitation status were assessed. The effect of the season and polymorphisms on seminal quality was evaluated by mixed ANOVA. Key results Both polymorphisms had an effect on membrane integrity and viable spermatozoa with low levels of ROS and without PS translocation, and Rsa I also on motile and DNA-intact spermatozoa. An interaction between both polymorphisms was found, pointing to a negative effect on seminal quality of carrying the T or A allele in homozygosity. Differences were higher in the reproductive than in the non-reproductive season. Conclusions Mutations substituting C by T and G by A at Rsa I and Mnl I polymorphic sites, respectively, in the MTNR1A gene in rams could decrease the seminal quality. Implications Genotyping of rams based on melatonin receptor 1A could be a powerful tool in sire selection.

Rs4862705 in the melatonin receptor 1A gene is associated with renal function decline in type 1 diabetes individuals.

The pathogenesis of chronic diabetes complications has oxidative stress as one of the major elements, and single-nucleotide polymorphisms (SNPs) in genes belonging to antioxidant pathways modulate susceptibility to these complications. Considering that melatonin is a powerful antioxidant compound, our aim was to explore, in a longitudinal cohort study of type 1 diabetes (T1D) individuals, the association of microvascular complications and SNPs in the gene encoding melatonin receptor 1A (MTNR1A). Eight SNPs in MTNR1A were genotyped in 489 T1D individuals. Besides cross-sectional analyses of SNPs with each one of the microvascular complications (distal polyneuropathy, cardiovascular autonomic neuropathy, retinopathy, and diabetic kidney disease), a longitudinal analysis evaluated the associations of SNPs with renal function decline in 411 individuals followed up for a median of 8 years. In a subgroup of participants, the association of complications with urinary 6-sulfatoxymelatonin (aMT6s) concentration was investigated. The group of individuals with a renal function decline ≥ 5 mL min-1 1.73 m-2 year-1 presented a higher frequency of the A allele of rs4862705 in comparison with nondecliners, even after adjustment for confounding variables (OR = 1.84, 95% CI = 1.20-2.82; p = 0.0046). No other significant associations were found. This is the first study showing an association between a variant in a gene belonging to the melatonin system and renal function decline in the diabetic setting.

Association of melatonin receptor 1 A with litter size in sheep: A review.

Sheep are a valuable livestock species worldwide, providing meat, milk, and various dairy products. This article aims to review the latest literature on the melatonin receptor 1A (MTNR1A) gene as a potential candidate gene associated with reproductive traits, particularly the litter size trait in sheep, by searching various databases for available literature. Studies have shown that different parts of the MTNR1A gene play various roles in sheep. By identifying marker genes associated with reproductive traits in MTNR1A polymorphisms linked to the litter size trait, breeders can achieve a faster selection response in sheep breeding by recognizing the genomic region where these genes are located and understanding their physiological functions. Therefore, highlighting the literature on these functions and their association with reproductive traits may contribute to improving the genetic makeup during sheep breeding.

Association study of melatonin receptor 1 A with litter size in sheep: A review

Sheep are a valuable livestock species worldwide, providing meat, milk, and various dairy products. This article aims to review the latest literature on the melatonin receptor 1A (MTNR1A) gene as a potential candidate gene associated with reproductive traits, particularly the litter size trait in sheep, by searching various databases for available literature. Studies have shown that different parts of the MTNR1A gene play various roles in sheep. By identifying marker genes associated with reproductive traits in MTNR1A polymorphisms linked to the litter size trait, breeders can achieve a faster selection response in sheep breeding by recognizing the genomic region where these genes are located and understanding their physiological functions. Therefore, highlighting the literature on these functions and their association with reproductive traits may contribute to improving the genetic makeup during sheep breeding.

Photoperiod Induces DNA Methylation Changes in the Melatonin Receptor 1A Gene in Ewes

Research has shown that MTNR1A plays an essential role in the estrus cycle and seasonal reproduction changes in sheep. However, few people have focused on the DNA methylation of MTNR1A by season or photoperiod. In this study, using qPCR and Western blotting, we measured the MTNR1A expression in the hypothalamus of ovariectomized and estradiol-treated (OVX + E2) sheep under different photoperiod treatment conditions. Subsequently, the core promoter of the MTNR1A gene was identified, and its methylation level in sheep exposed to different photoperiod treatments was measured by pyrosequencing. The results showed that MTNR1A gene expression significantly differed between the short 42-day photoperiod (SP42) and the LP42 or combined SP-LP42 treatment groups (p < 0.05). In addition, we determined that the core MTNR1A promoter region was within 540 bp upstream of the transcriptional start site (TSS) and that the DNA methylation levels at CpG sites in the SP42 vs. LP42 and SP42 vs. SP-LP42 groups significantly differed. Finally, a significant negative correlation (p < 0.001) between gene expression and DNA methylation levels was revealed, suggesting that photoperiod may induce DNA methylation of the MTNR1A gene and thus change its expression. The findings provide valuable bases for the further study of seasonal reproduction in sheep.

Melatonin receptor 1A (MTNR1A) gene linkage and association to type 2 diabetes in Italian families.

Melatonin regulates the mammalian circadian rhythm and plays metabolic functions such as glucose homeostasis. Both melatonin receptors (MTNR1A and MTNR1B, encoded by the MTNR1A and MTNR1B genes, respectively) are expressed in pancreatic beta cells and mediate the glucometabolic roles of melatonin as well as insulin secretion. The MTNR1B gene is a well-known genetic risk factor in type 2 diabetes (T2D); however, little is known about the involvement of the MTNR1A gene in here T2D. We aimed to investigate whether MTNR1A is linked to and/or associated with familial T2D. We genotyped 14 single nucleotide polymorphisms within the MTNR1A gene in 212 peninsular Italian families with T2D. We performed parametric linkage and linkage disequilibrium analyses to investigate the role of MTNR1A variants in conferring T2D risk. We considered variants statistically significant if conferring linkage or linkage disequilibrium with p < 0.05. We found 3 novel variants (rs62350392, rs2119883, and rs13147179) significantly linked to and/or associated with T2D in multigenerational Italian families. This is the first study to report MTNR1A as a novel risk gene in T2D. Functional studies are needed to confirm these results.

O-032 Polymorphisms of the melatonin receptor 1A (MTNR1A) gene of Rasa Aragonesa rams affect their fertility after artificial insemination

O-032 Polymorphisms of the melatonin receptor 1A (MTNR1A) gene of Rasa Aragonesa rams affect their fertility after artificial insemination

Association of Melatonin receptor 1A (MTNR1A) gene polymorphism with seasonal suppression of fertility in buffaloes

The polymorphism in Melatonin receptor 1A (MTNR1A) gene and its association with reproductive cyclicity (cyclic, n=51; non-cyclic, n=50) during summer season and age at first calving (&lt;3.5 years, n=38; &gt;3.5 years, n=60) was investigated in buffaloes subjected to blood sampling. Polymerase chain reaction (PCR) of genomic DNA was carried out using three primers viz. 824 bp (primer pair 1), 856 bp (primer pair 2) and 268 bp (primer pair 3) corresponding to exon-II of MTNR1A gene. Restriction fragment length polymorphism was performed using PCR products of primer pair 1 and 2. The digestion of PCR product of primer pair 1 with restriction enzymes viz. MnII, RsaI or Eco3II generated total restriction sites respectively as 14, 4 and 5. Based upon differential restriction sites, six genotypes revealed in buffaloes using MnII were MM-1 to MM-6, four genotypes using RsaI were RR-1 to RR-4, and four genotypes using Eco3II were EE-1 to EE-4. The digestion of PCR product of primer pair 2 with MnII, RsaI or Eco3II generated restriction sites respectively as 13, 5 and 6. Based upon differential restriction sites, six genotypes revealed using MnII were mm-1 to mm-6, five genotypes using RsaI were rr-1to rr-5, and three genotypes using Eco3II were ee-1 to ee-3. For primer pair 3, single stranded conformational polymorphism analysis exhibited 5 genotypes viz. AA, BB, AB, CC and DD. The results revealed that the buffaloes during summer had polymorphic genotypes for MTNR1A gene as buffaloes showing reproductive cyclicity had MM-3, MM-4, RR-2, EE-3, mm-2, mm-4, rr-3, ee-3, CC and DD genotypes, whereas their non-cyclic counterparts had MM-2, MM-6, EE-4, mm-3, mm-6, AA, BB and AB genotypes. However, no such differences were recorded with respect to age at first calving. In conclusion, polymorphic genotypes of MTNR1A gene may be considered as genetic markers to identify buffaloes with better reproductive potential during summer season.

Influence of the polymorphisms of the melatonin receptor 1A (MTNR1A) gene on the distribution of MT1 and MT2 melatonin receptors in ram sperm

Melatonin can exert some of its functions by binding to specific membrane receptors, mainly MT1 and MT2 in mammals. The melatonin receptor 1A (MTNR1A) gene exhibits several polymorphic sites. Certain RsaI genotypes have been related to an advance in the mating activity of ram-lambs or to a more intense reproductive behavior in adult rams. However, the influence of those genotypes in the location of melatonin receptors in ram spermatozoa remains unknown. The aim of this work was to evaluate whether RsaI polymorphisms of the MTNR1A gene influence the cellular distribution of MT1 and MT2 receptors in ram sperm. For this purpose, ejaculates from 18 previously genotyped Rasa Aragonesa rams were collected, and the location of melatonin receptors was assessed by indirect immunofluorescence, using anti-MT1 (Abnova Corporation, Cat# H00004543- A01, RRID: AB_462681) and anti-MT2 (OriGene, Cat#AP01322PU-N, RRID: AB_1619198) antibodies. Statistical analysis (χ²) was performed using SPSS Statistics v.26. For the MT1 receptor, G/A rams had a higher percentage of type I spermatozoa (labelling all over the head and tail) but lower rates of immunotypes II (reactivity at the equatorial and post-acrosomal regions, neck and tail) and III (only the equatorial region and tail labelled) when compared to G/G and A/A rams (P<0.01). Immunotype IV (only the flagelum stained) was also lower in G/A rams than in G/G (P<0.05). For the MT2 receptor, G/A rams had higher percentages of type AP spermatozoa (acrosome and post- acrosome equally stained), and lower percentages of type A (more intensity in acrosome than post-acrosome) when compared to G/G and A/A rams (P<0.001). Furthermore, G/G rams had a higher percentage of type P spermatozoa (more intense staining on post- acrosome than acrosome) than G/A and A/A rams (P<0.01). In conclusion, these results suggested that polymorphisms of the MTNR1A gene could influence the distribution of MT1 and MT2 receptors in ram sperm, which could have consequences on the direct effects of melatonin on spermatozoa. [Research supported by PID2020-113239RB-I00 and A07_20R. V.P-D. has a predoctoral contract from the Diputación General de Aragón]

Influence of melatonin receptor 1A (MTNR1A) gene polymorphisms on melatonin synthetizing-enzymes and melatonin receptors gene expression in ram

Influence of melatonin receptor 1A (MTNR1A) gene polymorphisms on melatonin synthetizing-enzymes and melatonin receptors gene expression in ram

Molecular description of melatonin receptor 1A gene in Iraqi buffalo

The water buffalo has a seasonal reproductive pattern with reduced sexual activity during the longer photoperiod. The goal of this study was to identify the single nucleotide polymorphism (SNP) of melatonin receptor 1A (MTNR1A) gene in Iraqi buffalo cows and 3D structure of its protein and phylogeny with other sequences around the world. The 824 bp fragment of exon II of the MTNR1 A gene was amplified from 190 buffalo cows (4-5 years old) genomic DNA belonging to local breeders in Al-Chibayish Marshes, Southern Iraq. Amplified PCR products underwent custom sequencing at the two ends (5′ and 3′ ends). Five separate polymorphism sites, the 1st included 52 animals with 19 mutations (12 missense), the 2nd included 39 animals with 18 mutations (11 missense), the 3rd included 35 animals with 18 mutations (12 missense), the 4th included 32 animals with 18 mutations (12 missense) and the 5th included 32 animals with 14 mutations (8 missense). These polymorphic sites with accession numbers LC565046, LC565047, LC565709, LC565710 and LC565711 respectively were registered in gene bank. The phylogenetic tree reveals that in some of the Iraqi buffalo, the sequences of MTNR1A gene has identical to the Italian buffalo (GU817415), and the Brazilian buffalo (JN689386). Data revealed a marked difference in the fifth polymorphism sites' 3D protein structure because of the mutations. In conclusion, as a result of mutations, the gene MTNR1A in Iraqi buffalo has polymorphisms; these polymorphisms may be linked to gene function, Therefore, further studies are needed to connect the polymorphisms of this gene with the productive and reproductive traits.

High association of a novel variant in the adiponectin gene with the litter size in Awassi ewes

Flock productivity is affected by reproductive traits controlled by many factors such as ovulation rate, hormones, and genetics. Many genes are associated with fertility and other features related to it such as melatonin receptor 1A ( MNTR1A ) gene, inhibin βA ( INHBA) gene, insulin-like growth factor-I ( IGF-1 ) gene, and prolactin gene, and many other new candidates, adiponectin gene ( ADIPOQ ) is one of them, which are associated with reproduction and fertility. This study aimed to evaluate the genetic variation of the ADIPOQ gene concerning the litter size of Awassi ewes. Genomic DNA isolated from 114 Awassi ewes produced single lambs and 84 Awassi ewes produced twin lambs. By polymerase chain reaction (PCR), we amplified all three exons (368 bp, 448 bp, and 363 bp) of the ADIPOQ gene (exons 1, 2, and 3). Three genotypes were found in the 368 bp amplicons, the CC, CA, and AA genotypes. Novel mutation c.198473337C > A was discovered in the CA genotype through a sequencing reaction. This single nucleotide polymorphism (SNP) showed a highly significant ( P ≤ 0.01) association with litter size, in that the sheep with this SNP had a larger litter size than those without it. The ewes with the AA genotype had 1.97 lambs more than those with the CC and CA genotypes. Using logistic regression, the c.198473337C > A SNP was confirmed to be responsible for increasing the litter size. In conclusion, the c.198473337C > A SNP appears to have an interesting and positive impact on reproductive traits (especially litter size) in Awassi sheep. In light of these data, the genetic variant of the ADIPOQ gene could be used for developing marker-assisted selection programs to improve litter size in Awassi sheep.

Polymorphisms of the melatonin receptor 1A (MTNR1A) gene do not affect sexual activity, plasma testosterone concentrations or testicular characteristics of 8-month-old ram-lambs born in autumn

Thirty-nine autumn-born ram-lambs were used to study whether polymorphisms of the melatonin receptor 1A (MTNR1A) gene influence some reproductive parameters of Oct-born ram-lambs at 8 months of age. Animals were genotyped for their RsaI (CC, n=24; CT, n=6; TT, n=9) and MnlI (GG, n=27; GA, n=6; AA, n=6) allelic variants of the MTNR1A gene. Liveweight (LW) was recorded bi-weekly until Jun, and scrotal perimeter (SP) was recorded once per month. From mid-Jan, blood samples were collected weekly to measure plasma testosterone concentrations. In mid-Jun, individual serving-capacity tests were performed. Testicular ultrasonography was performed at the end of the experiment. The effects of the week and gene polymorphism on LW, scrotal perimeter, and plasma testosterone concentrations were evaluated statistically by the GLM for repeated measures procedure. LW, SP, and plasma testosterone concentrations were significantly (P&lt;0.001) affected by week, but neither of the polymorphisms of the melatonin receptor 1A (MTNR1A) gene affected these variables. In the serving tests, genotypes did not differ significantly in individual behaviors or the number of events (CC: 24.1±3.2, CT: 26.3±13.0, TT: 16.8±4.8, GG: 22.0±3.0, GA: 21.0±6.7, AA: 27.8±12.7). Testicular features assessed by ultrasonography did not differ significantly among genotypes. In conclusion, the polymorphisms of the melatonin receptor 1A (MTNR1A) gene did not have an effect on the reproductive characteristics of autumn-born ram lambs, based on serving capacity tests, testosterone secretion, and testicular measurements at 8 months of age.

Polymorphisms of the melatonin receptor 1A (MTNR1A) gene affect the sexual performance of Rasa Aragonesa rams without changing their social dominance

Polymorphisms of the melatonin receptor 1A (MTNR1A) gene affect the sexual performance of Rasa Aragonesa rams without changing their social dominance

​Body Size Traits and Association with the Genetic Polymorphism of Melatonin Receptor 1A (MTNR1A) Gene in Shuxuan Cattle

Background: Shuxuan cattle is one newly cultivated dual-purpose breed in Sichuan province, China, by crossing the indigenous Xuanhan cattle with external breeds. Body sizes have been widely regarded as the important breed characteristics in cattle. The current study was aimed to evaluate the body sizes and its molecular inherite marker for futhure herd improvement. Methods: In the present study, we first investigated a total of 11 body size traits and their overall distribution and pairwise relationships of 169 healthy Shuxuan cattle. Subsequently, the SNP c.A455G of melatonin receptor 1A (MTNR1A) gene were genotyped among 169 Shuxuan cattle and subjected to association analysis with body size traits. Result: We revealed that adult females have the mean withers height of 113.5 cm, body length of 131.8 cm, chest girth of 157.5 cm and hip height of 104.8 cm, respectively. Among all these traits, the highest correlation was observed in withers height and hip height with spearman’s coefficient of 0.85. We found that Shuxuan cattle had an average heterozygosity of 0.5008 and polymorphism information content of 0.3747. Accordingly to the very stringent criterion of Bonferroni multiple adjustments, only chest width was associated with different genotypes of this candidate SNP (P less than 0.05). The results provide an overall profile of the morphological and growth characteristics in Shuxuan cattle.

Melatonin Receptor Gene Polymorphism in Bipolar-I Disorder

In patients with Bipolar-I Disorder (BD-I), circadian rhythm and sleep disorders are frequently observed. Melatonin is a main regulatory hormone for the circadian rhythm. Certain studies have shown the relationship of melatonin receptor gene polymorphism with psychiatric diseases. In this study, it was aimed to investigate the relationship between BD-I and -184T>C (rs2119882) polymorphism in melatonin receptor 1A (MTNR1A) gene and -1193C>T (rs4753426) polymorphism in melatonin receptor 1B (MTNR1B) gene. The study included 108 patients diagnosed with BD-I and 95 healthy people as the control group. Real-time PCR (RT-PCR) method was used to evaluate the polymorphism of MTNR1A gene-184T>C. Genotyping of MTNR1B gene-1193C>T polymorphism was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In terms of MTNR1B gene-1193C>T polymorphism, homozygous CC genotype was found to be increased in BD-I patient group compared to the control group (p <0.05). Similarly, a statistically significant difference was found between the patients and the control group in terms of allele frequencies too (p <0.05). However, no relation between BD-I and MTNR1A gene-184T>C polymorphism was found (p >0.05). The results of the study revealed that MTNR1B gene-1193C>T polymorphism may play a role in BD-I genetic etiology and may be among the causes of sleep disorder and circadian rhythm disorder seen in these patients.

Polymorphisms of the melatonin receptor 1A (MTNR1A) gene influence the age at first mating in autumn-born ram-lambs and sexual activity of adult rams in spring

The aim of this study was to determine whether polymorphisms of the melatonin receptor 1A (MTNR1A) gene influence the age at first mating in autumn-born ram-lambs and influence the out-of-season sexual activity of adult rams. In experiment 1, 24 Rasa Aragonesa ram-lambs born in September were genotyped for their RsaI and MnlI allelic variants of the MTNR1A gene, and the date of their first mounting with ejaculation after a period of semen collection training was documented. In experiment 2, the reproductive behavior, testicle size, and plasma testosterone concentrations of 18 adult rams (6 rams for each RsaI genotype) were recorded at the beginning (March) and end (May) of the seasonal anestrus. The number of days of training to achieve the first mating with ejaculation in T/T (C/C: 85.17 ± 12.08 C/T: 86.60 ± 18.87; T/T; 26.50 ± 24.50 d; P < 0.05), and G/G ram-lambs (G/G: 51.57 ± 14.99; A/G: 95.58 ± 10.95 d; P < 0.05) was significantly fewer than it was in the other genotypes. Likewise, for the RsaI genotype, 55% of the vulva-sniffing (P < 0.001), 48% of the approaches (P < 0.01), 48% of the mountings (P < 0.05) and 49% total activities (P < 0.001) were performed by T/T rams in March, and 50% of the sexual events in May (P < 0.001). For the Mnll variant, G/G rams performed a significantly (P < 0.001) larger proportion of the vulva-sniffing (41%), approaches (46%) and total activities (40%) in March, and 52% of the vulva-sniffing (P < 0.001), 43%, of the approaches (P < 0.001), 46% of the mountings (P < 0.05), and 47% of the total activities (P < 0.001) in May. Scrotal circumference, testicular volume, and plasma testosterone concentrations did not differ significantly among genotypes. Results confirmed that the polymorphisms of the MTNR1A gene sequence can influence reproductive performance in young and adult rams. Autumn-born ram-lambs that carried the T/T or G/G genotype had an advanced ability to reproduce, and T/T or G/G adult rams exhibited the most intense reproductive behavior. Genotyping might be a useful procedure for identifying the correct and rational use of rams in modern sheep farming.

Melatonin supplement induced the hair follicle development in offspring rex rabbits.

Previous studies have shown that the administration of melatonin (MT) to early post-natal fur-bearing animals increases the numbers of hair follicles (HFs). In this study, the effect of maternal MT supplementation on the HF development in offspring was investigated. To explore the potential underlying mechanisms, the expression of the melatonin receptor 1A (MTNR1A) gene was determined in the offspring. The Rex rabbit was the animal model, and 79 same-day-pregnancy females were randomly assigned to either a control (n=39) or MT treatment (n=40) group, and 10mg MT microcapsules was implanted at the base of the neck of rabbits in the treatment group. Skin, lung, liver, muscle, kidney, heart and duodenum samples were collected from the newborn rabbits. The results showed that MT improved fur quality in the offspring rabbits by reducing the diameter of primary and secondary HFs, and increasing the HF population. MT did not affect the reproductive performance of female rabbits, and it did affect the blood levels of thyroid-stimulating hormone, prolactin and MT. In the offspring rabbits, MT significantly stimulated MTNR1A gene expression in the skin and heart (p<.01), whereas MTNR1A gene expression was significantly suppressed in the liver and kidney (p<.05). These results revealed that maternal MT supplementation increased HF density, reduced hairiness and improved the fur quality in Rex rabbit offspring. Maternal MT supply may modulate the responses of HFs in the offspring by upregulating the expression of MTNR1A in the skin. In this study, implantation of low-dose MT did not affect the reproductive performance of female rabbits or on the growth of their offspring.

Variation near MTNR1A associates with early development and interacts with seasons.

Melatonin is a circadian regulatory hormone with neuroprotective properties. We have previously demonstrated the association of thegenetic variant rs12506228 near the melatonin receptor 1A gene (MTNR1A) with intolerance to shift-work. Furthermore, this variant has been connected to Alzheimer's disease. Because of the previously suggested role of melatonin signalling in foetal neurocognitive and sleep development, we studied here the association of rs12506228 with early development. The study sample comprised 8-month-old infants from the Finnish CHILD-SLEEP birth cohort (n=1,301). Parental questionnaires assessed socioemotional, communication and motor development, as well as sleep length and night awakenings. The A allele of rs12506228 showed an association with slower socioemotional (p=.025) and communication (p=.0098) development, but no direct association with sleep. However, the association of the Finnish seasons with infant sleep length interacted with rs12506228. Taken together, rs12506228 near MTNR1A, which has been previously linked to adult and elderly traits, is shown here to associate with slower early cognitive development. In addition, these results suggest that the darker seasons associate with longer infant sleep time, but only in the absence of the rs12506228 AA genotype. Because the risk allele has been connected to fewer brain MT1 melatonin receptors, these associations may reflect the influence of decreased melatonin signalling in early development.

Polymorphisms of the melatonin receptor 1A gene that affects the reproductive seasonality and litter size in Small Tail Han sheep.

Previous researches have shown that MTNR1A plays an essential role in sheep reproduction. However, most researches focused more on the reproductive seasonality of sheep, and few scientists had studied the association of polymorphisms of the MTNR1A gene with ovine litter size and reproductive seasonality. Therefore, we chose MTNR1A gene to detect its novel sequence polymorphisms and population genetics and analyse their association with seasonal reproduction and litter size in ewes. The mRNA expression level in hypothalamus, pituitary and ovary was also detected. In this study, five polymorphisms (g.15118664G > T, g.15118683C > T, g.15118756C > T, g.15118774C > T and g.15118951G > A) were identified in exon 2. Most importantly, the g.15118683C > T and g.15118951G > A were significant difference between year‐round oestrous sheep and seasonal oestrous sheep (p < .01), and g.15118756C > T had a great effect on litter size of Small Tail Han sheep (p < .05). In addition, the mRNA expression level of MTNR1A in the hypothalamus of polytocous Small Tail Han sheep was significantly higher than that in monotocous Small Tail Han sheep (p < .01) and the expression of MTNR1A in the hypothalamus of year‐round oestrous sheep was significantly higher than that in seasonal oestrous sheep (p < .01). Polymorphisms in exon 2 may regulate the reproductive seasonality and litter size of ewes by influencing gene expression to regulate the reproductive seasonality and litter size of ewes. Our studies provided useful guidance in marker‐assisted selection of the litter size in Small Tail Han sheep.