[Impact of plateau environment on seminal characteristics of native Tibetans and immigrated Tibetan Hans].

OBJECTIVE: To investigate the characteristics of the semen parameters of native Tibetans and immigrated Tibetan Hans in the high-altitude area and analyze the influence of altitude adaptation on male fertility. METHODS: This study included 1 563 infertile male patients, including 698 native Tibetans and 865 immigrated Tibetan Hans, and 56 normal fertile men, including 33 native Tibetans and 23 Tibetan Hans. We obtained semen samples from the subjects for routine semen analysis and sperm DNA fragmentation index (DFI) examination and collected peripheral blood for determination of the reproductive hormone levels. RESULTS: In the infertile patients, the native Tibetans, as compared with the immigrated Hans, showed significantly higher incidence rates of azoospermia (5.87% vs 2.89%, P <0.05), severe oligozoospermia (3.15% vs 1.73%, P <0.05) and abnormal seminal viscosity (43.12% vs 25.89%, P<0.01), but no statistically significant differences in the percentages of normozoospermia (81.08% vs 87.39%, P >0.05), oligozoospermia (5.44% vs 3.93%, P >0.05), severe asthenozoospermia (4.44% vs 4.04%, P >0.05) or severe teratozoospermia (4.58% vs 6.59%, P >0.05). In the normal fertile men, there were no statistically significant differences between the native Tibetans and immigrated Hans in age (ï¼»32.42 ± 4.82ï¼½ vs ï¼»34.57 ± 6.01ï¼½ yr, P >0.05), sperm concentration (ï¼»143.69 ± 85.74ï¼½ vs ï¼»155.11 ± 82.56ï¼½ ×106/ml, P >0.05), straight line velocity (ï¼»25.74 ± 3.94ï¼½ vs ï¼»27.24 ± 3.46ï¼½ µm/s, P >0.05), percentage of morphologically normal sperm (ï¼»8.22 ± 4.35ï¼½ vs ï¼»7.28±2.46ï¼½ %, P >0.05), total testosterone concentration (ï¼»17.97 ± 2.98ï¼½ vs ï¼»15.72 ± 6.38ï¼½ nmol/L, P >0.05), or follicle stimulating hormone level (ï¼»5.51 ± 1.62ï¼½ vs ï¼»4.17 ± 2.08ï¼½ IU/L, P >0.05). However, the immigrated Hans, in comparison with the native Tibetans, exhibited a higher sperm motility (ï¼»79.75 ± 14.67ï¼½ vs ï¼»66.58 ± 17.21ï¼½%, P <0.05), a lower curvilinear velocity (ï¼»60.97 ± 2.71ï¼½ vs ï¼»71.14 ± 82.13ï¼½ µm/s, P <0.05) and a lower level of luteinizing hormone (ï¼»4.28 ± 1.20ï¼½ vs ï¼»5.84 ± 1.15ï¼½ IU/L, P <0.05). CONCLUSIONS: During the acclimatization to the plateau hypoxia environment, the immigrated Tibetan Hans undergo adaptive changes in sperm concentration and motility and have lower incidence rates of azoospermia and severe oligozoospermia than native Tibetan males.

Multi-micronutrient supplementation during pregnancy for prevention of maternal anaemia and adverse birth outcomes in a high-altitude area: a prospective cohort study in rural Tibet of China.

Anaemia during pregnancy, characterised by Hb <110 g/l, is a specific risk factor for adverse maternal and perinatal outcomes in developing countries. The objective of this study was to determine the effectiveness of daily antenatal supplementation with multiple micronutrients (MMN) compared with folic acid (FA) on the occurrence of anaemia among pregnant women and their infants' health in a high-altitude area. A prospective cohort study was carried out in two rural counties in Tibet from 2007 to 2012. A total of 1149 eligible pregnant women were allocated daily supplementation with FA in one county and MMN containing a recommended allowance of twenty-three vitamins and minerals in another county starting ≤24 weeks of gestation and continuing until delivery. Compared with the FA group, prenatal supplementation with MMN was significantly associated with reduced odds of anaemia in the third trimester. This was demonstrated in the primary outcome, with an adjusted OR (AOR) of 0·63; 95 % CI 0·45, 0·88 and P=0·007 and also reduced odds of preterm delivery (AOR: 0·31; 95 % CI 0·15, 0·61; P=0·001). There was no difference between MMN and FA groups in mean birth weight (adjusted mean difference: 36·78; 95 % CI -19·42, 92·98 g; P=0·200), whereas MMN supplementation significantly reduced the odds of low-birth weight (LBW) babies (AOR: 0·58; 95 % CI 0·36, 0·91; P=0·019). In conclusion, the antenatal MMN supplementation in rural Tibet is associated with a reduction of maternal anaemia in the third trimester, and may potentially decrease the risk of preterm delivery and LBW babies.

Source and health risk of urinary neonicotinoids in Tibetan pregnant women.

High altitude could influence the level of exposure to neonicotinoids, but relevant data remain limited for people living in Tibet. We investigated 476 Tibetan pregnant women from Lhasa of Tibet, China in 2021 and measured eight neonicotinoids and four metabolites in urine. Food consumption was investigated by a food frequency questionnaire. Health risk was assessed by using hazard quotient (HQ) and hazard index (HI) based on acceptable daily dose or chronic reference dose. Neonicotinoids and metabolites were overall detected in 56.5% of urine samples with a median concentration being 0.73 µg g-1 creatinine. Four neonicotinoids or metabolites were detected in more than 10% of urine samples, including N-desmethyl-acetamiprid (47.5%), clothianidin (15.5%), thiamethoxam (16.0%), and imidacloprid (10.5%). Annual household income, family smoking, and pre-pregnancy body mass index were associated with the detection frequencies of neonicotinoids. Pregnant women with a higher consumption frequency of wheat, rice, fresh vegetable, fresh fruit, beef and mutton, fresh milk, yoghourt, candy and chocolate, or carbonated drinks had a higher detection frequency of neonicotinoids. Both HQ and HI were less than one. There was an evident exposure to neonicotinoids in Tibetan pregnant women with both plant- and animal-derived food items as exposure sources, but a low health risk was found based on current safety thresholds.

Exposure of Tibetan pregnant women to antibiotics in China: A biomonitoring-based study.

Tibetan people are one Chinese ethnic minority living in Qinghai-Tibet Plateau with an average altitude of more than 4500 m. High altitude could cause a different antibiotic exposure, but relevant information is limited in Tibetan people. We investigated 476 Tibetan pregnant women in Lhasa, Tibet in 2021 and measured 30 antibiotics from five categories in urine, including 13 veterinary antibiotics (VAs), five human antibiotics (HAs), and 12 human/veterinary antibiotics (H/VAs). Food consumption was investigated by a brief food frequency questionnaire. Health risk was assessed by hazard quotient (HQ) and hazard index (HI) based on acceptable daily intakes (ADIs). All antibiotics were overall detected in 34.7% of urine samples with the 75th percentile concentration of 0.19 ng/mL (0.35 µg/g creatinine). HAs, VAs, and H/VAs were respectively detected in 5.3%, 13.0%, and 25.0% of urine samples, with the 95th percentiles of 0.01 ng/mL (0.01 µg/g creatinine), 0.50 ng/mL (0.99 µg/g creatinine), and 3.58 ng/mL (5.02 µg/g creatinine), respectively. Maternal age, smoking of family members, and housework time were associated with detection frequencies of HAs, VAs, or sum of all antibiotics. Pregnant women with a more frequent consumption of fresh milk, egg, yoghourt, poultry meat, and fish had a higher detection frequency of VAs or H/VAs. Only ciprofloxacin and tetracycline had a HQ of larger than one based on microbiological effect in 1.26% and 0.21% of pregnant women, respectively and a HI of larger than one was found in 1.47% of pregnant women. The findings suggested that there was an evident antibiotic exposure from various sources in Tibetan pregnant women with some basic characteristics of pregnant women as potential predictors and several animal-derived food items were important sources of exposure to antibiotic with a fraction of pregnant women in the health risk related to microbiological disruption of gut microbiota.

Same total normal forms sperm counts of males from Lhasa and Shanghai, China.

Male infertility may be caused by genetic and/or environmental factors that impair spermatogenesis and sperm maturation. High-altitude (HA) hypoxic environments represent one of the most serious challenges faced by humans that reside in these areas. To assess the influence of the plateau environment on semen parameters, 2,798 males, including 1,111 native Tibetans and 1,687 Han Chinese individuals living in the plains (HCILP) who underwent pre-pregnancy checkups, were enrolled in this study. The semen samples of males were evaluated to determine conventional sperm parameters, sperm morphology, and sperm movement. Reproductive endocrine hormones (REHs) were detected in 474 males, including 221 Tibetans and 253 HCILP. Due to recurrent abortions in partners, the DNA fragmentation index (DFI) of 133 native Tibetans and 393 HCILP individuals was further compared. Luteinizing hormone (LH) (4.94 ± 2.12 vs. 3.29 ± 1.43 U/L), prolactin (11.34 ± 3.87 vs. 8.97 ± 3.48 nmol/L), E2/T (0.22 ± 0.11 vs 0.11 ± 0.05), median total sperm motility (61.20% vs. 51.56%), and DFI (23.11% vs. 7.22%) were higher in males from plateau areas while median progressive motility (PR) (35.60% vs. 41.12%), total number of PR sperms (51.61 vs. 59.63 mil/ejaculate), percentage of normal form sperms (3.70% vs. 6.00%), curvilinear velocity (36.10 vs. 48.97 µm/s), straight-line (rectilinear) velocity (14.70 vs. 31.52 µm/s), estradiol (103.82 ± 45.92 vs. 146.01 ± 39.73 pmol/L), progesterone (0.29 ± 0.27 vs. 2.22 ± 0.84 nmol/L), testosterone (4.90 ± 1.96 vs. 14.36 ± 5.24 nmol/L), and testosterone secretion index (ratio of testosterone to LH) (33.45 ± 22.86 vs 145.78 ± 73.41) were lower than those in males from the plains. There was no difference in median total sperm number (157.76 vs. 151.65 mil/mL), sperm concentration (52.40 vs. 51.79 mil/mL), volume (3.10 vs. 3.10 mL), total normal form sperms (5.91 vs. 6.58 mil/ejaculate, p50), and follicle-stimulating hormone (FSH) levels (4.13 ± 2.55 U/L vs 3.82 ± 2.35 U/L) between the two groups of males. The REH and sperm parameters of males from HA hypoxic environments were adaptively altered. Although the total number of PR sperm decreased and DFI increased, the Tibetan population that lives at HAs has been found to grown continuously and rapidly. These results supplement prior findings regarding the impact of HA on male reproductive function.

GCH1 plays a role in the high-altitude adaptation of Tibetans.

Tibetans are well adapted to high-altitude hypoxia. Previous genome-wide scans have reported many candidate genes for this adaptation, but only a few have been studied. Here we report on a hypoxia gene ( GCH1, GTP-cyclohydrolase I), involved in maintaining nitric oxide synthetase (NOS) function and normal blood pressure, that harbors many potentially adaptive variants in Tibetans. We resequenced an 80.8 kb fragment covering the entire gene region of GCH1 in 50 unrelated Tibetans. Combined with previously published data, we demonstrated many GCH1 variants showing deep divergence between highlander Tibetans and lowlander Han Chinese. Neutrality tests confirmed a signal of positive Darwinian selection on GCH1 in Tibetans. Moreover, association analysis indicated that the Tibetan version of GCH1 was significantly associated with multiple physiological traits in Tibetans, including blood nitric oxide concentration, blood oxygen saturation, and hemoglobin concentration. Taken together, we propose that GCH1 plays a role in the genetic adaptation of Tibetans to high altitude hypoxia.

EP300 contributes to high-altitude adaptation in Tibetans by regulating nitric oxide production.

The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene EP300 (histone acetyltransferase p300), we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans. The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans, with a group of variants showing allelic divergence between Tibetans and lowland reference populations, including Han Chinese, Europeans, and Africans. Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation. More importantly, genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide (NO) concentration. Collectively, we propose that EP300 harbors adaptive variants in Tibetans, which might contribute to high-altitude adaptation through regulating NO production.