生殖生物学 (BOR) 是生殖研究学会的官方期刊，发表关于生殖生物学领域广泛主题的原创研究，以及对当前重要或争议主题的评论。 BOR 一直是发表生殖生物学领域原创研究的引用率最高的期刊之一。

Biology of Reproduction is the official journal of the Society for the Study of Reproduction, publishing original research on a wide range of topics in the field of reproductive biology, as well as commentary on current important or controversial issues. It has consistently been one of the most highly cited journals for original research in the field of reproductive biology.

《Biology of Reproduction》是生殖研究学会的官方期刊，发表关于生殖生物学领域的原创研究，涵盖广泛的主题，并对当前重要或有争议的议题进行评论。该期刊一直是生殖生物学领域中引用率最高的原创研究发表平台之一。

Biology of Reproduction

Maternal liver undergoes structural and metabolic changes during pregnancy to meet the demands of the developing fetus. In rodents, this involves increased liver weight, but the mechanism remains unclear. To address this, we analyzed the histology, gene expression, and DNA methylation of livers of nonpregnant and pregnant C57/BL6 mice. Gestational liver growth in pregnant mice was accompanied by increased hepatocyte area and lower cell density (days 14 and 18). Expression of cell proliferation markers was increased on days 14 and 18. A total of 115 genes were differentially expressed on day 14 and 123 genes on day 18 (79 on both days). Pathway analysis indicated that pregnancy involves progressive increase in cell proliferation and decreased apoptosis. This was confirmed using archived data from the FVB wild-type mouse liver transcriptome. Four differentially DNA methylated and two differentially DNA hydroxymethylated regions identified on days 14 and 18 by methylome-wide analysis, but were not associated with altered gene expression. Long interspersed nuclear element-1 hypomethylation on days 14 and 18 was accompanied by increased ten-eleven translocase-2 and decreased DNA methyltransferase 3a and 3b expression. These findings suggest that gestational liver growth involves increased mitosis and hypertrophy, and decreased apoptosis contingent on pregnancy stage. Such changes may involve repetitive sequence, but not gene specific, DNA methylation.

Leonie R Price

Karen A Lillycrop

Nicola A Irvine

Mark A Hanson

Graham C Burdge

Transcriptome-wide analysis suggests that temporal changes in the relative contributions of hyperplasia, hypertrophy and apoptosis underlie liver growth in pregnant mice†

转录组范围分析表明，怀孕小鼠肝脏生长由增殖、肥大和凋亡相对贡献的时间变化所驱动†

A repeatable procedure for fertilization of bovine ova in vitro is described. Oocytes were recovered from ovarian follicles or from oviducts near the time of ovulation following treatment of donors with pregnant mare's serum gonadotropin (PMSG) and prostaglandin F2 alpha (PGF2 alpha). For in vitro capacitation semen was incubated, then high ionic strength treated and subsequently incubated in defined medium prior to insemination of oocytes. In one experiment frozen bull semen was successfully used. In experiments with 4 bulls (B, C, D, F), 34 (43.6%) of 78 ova and 13 (19.7%) of 66 follicular oocytes were fertilized in vitro. In the last series (spermatozoa from Bull F) the fertilization of 22 (62.9%) of 35 tubal ova was achieved. In vitro development proceeded to the 8-cell stage. No fertilization in vitro followed use of one male (Bull E), even though his spermatozoa could penetrate zona-free hamster ova in vitro, and higher than usual bacterial contamination of his semen was implicated as the probable cause. Findings suggested vigorous progressive sperm motility and acrosome integrity to be important features of good sperm samples. In one experiment a 4-cell stage embryo was transferred with the result that the recipient gave birth to a normal bull calf on June 9, 1981. The first calf resulting from in vitro fertilization has been found to be completely normal.

Benjamin G. Brackett

Daniel Bousquet

Melinda L. Boice

William J. Donawick

James F. Evans

Michael A. Dressel

Normal Development Following In Vitro Fertilization in the Cow

牛体外受精后的正常发育

Abstract The key event in placentitis-induced preterm labor is myometrial activation with the subsequent initiation of labor. However, the molecular mechanisms underlying myometrial activation are not fully understood in the mares. Therefore, the equine myometrial transcriptome was characterized during placentitis (290.0 ± 1.52 days of GA, n = 5) and the prepartum period (330 days of GA, n = 3) in comparison to normal pregnant mares (289.8 ± 2.18 days of GA, n = 4). Transcriptome analysis identified 596 and 290 DEGs in the myometrium during placentitis and the prepartum period, respectively, with 138 DEGs in common. The placentitis DEGs included eight genes (MMP1, MMP8, S100A9, S100A8, PI3, APOBEC3Z1B, RETN, and CXCL2) that are exclusively expressed in the inflamed myometrium. Pathway analysis elucidated that inflammatory signaling, Toll-like receptor signaling, and apoptosis pathways dominate myometrial activation during placentitis. The prepartum myometrium was associated with overexpression of inflammatory signaling, oxidative stress, and 5-hydroxytryptamine degradation. Gene ontology enrichment analysis identified several chemoattractant factors in the myometrium during placentitis and prepartum period, including CCL2, CXCL1, CXCL3, and CXCL6 in common. Upstream regulator analysis revealed 19 potential upstream regulators in placentitis dataset including transcription regulators (E2F1, FOXM1, HIF1A, JUNB, NFKB1A, and STAT1), transmembrane receptors (FAS, ICAM1, SELP, TLR2, and TYROBP), growth factors (HGF and TGFB3), enzymes (PTGS2 and PRKCP), and others (S100A8, S100A9, CD44, and C5AR1). Additionally, three upstream regulators (STAT3, EGR1, and F2R) were identified in the prepartum dataset. These findings revealed the key regulators and pathways underlying myometrial activation during placentitis, which aid in understanding the disease and facilitate the development of efficacious therapies.

H El-Sheikh Ali

Y L Boakari

S C Loux

P Dini

K E Scoggin

A Esteller-Vico

T Kalbfleisch

B A Ball

Transcriptomic analysis reveals the key regulators and molecular mechanisms underlying myometrial activation during equine placentitis†

转录组分析揭示了马子宫内膜炎期间子宫肌层激活的关键调控因子和分子机制†

Fungi of the Fusarium species can infect food and feed commodities and produce the mycotoxins zearalenone (ZEA) and deoxynivalenol (DON). Since both toxins have been reported to reduce fertility, the mechanisms of ZEA and DON on inhibition of oocyte maturation were examined. Pig oocytes were matured in the presence of ZEA (a mycotoxin with estrogenlike activity), 17beta-estradiol, and DON (all 3.12 μmol/L). Zearalenone, 17beta-estradiol, and DON inhibited oocyte maturation and caused approximately 34% of the oocytes to form an aberrant spindle. Different ratios of ZEA:DON did not lead to a more severe inhibition of oocyte maturation. Both mycotoxins caused abnormal formation of the meiotic spindle. The developmental competence of oocytes matured in the presence of mycotoxins was further investigated after in vitro fertilization. Presence of ZEA (3.12 μmol/L) during maturation reduced the percentages of oocytes that cleaved and formed a blastocyst to about 12%, compared with 25% of control oocytes. Maturation in the presence of equimolar concentrations of DON was not compatible with development. The ploidy of blastomeres from blastocysts derived from mycotoxin-exposed oocytes was analyzed with fluorescent in situ hybridization. All blastocysts, even those from the control group, contained at least one blastomere with abnormal ploidy, but the variation in the percentages of aneuploid blastomeres was significantly larger in embryos from oocytes exposed to mycotoxins. It is concluded that ZEA and DON can lead to abnormal spindle formation, leading to less fertile oocytes and embryos with abnormal ploidy, and that the effects of ZEA and DON are not synergistic.

Hassan Malekinejad

Eric J. Schoevers

Ineke J.J.M. Daemen

Carla Zijlstra

Ben Colenbrander

Johanna Fink-Gremmels

Bernard A.J. Roelen

Exposure of Oocytes to the Fusarium Toxins Zearalenone and Deoxynivalenol Causes Aneuploidy and Abnormal Embryo Development in Pigs1

玉米赤霉烯酮和脱氧雪腐镰刀菌烯醇暴露导致猪卵母细胞非整倍体及胚胎发育异常1

Abstract Deoxynivalenol (DON) is one of the most prevalent Fusarium mycotoxins, which cause detrimental effects on human and animal reproductive systems by inducing oxidative stress. Increasing evidence has suggested the potential roles of melatonin in protecting granulosa cells from oxidative injury, but the underlying mechanisms remain largely elusive. Here, we demonstrated that suppression of FOXO1 and endoplasmic reticulum (ER) stress was engaged in melatonin-mediated protection against oxidative damage in human granulosa cells upon DON exposure in vitro. DON induced excess reactive oxygen species accumulation, cells viability loss, reduced estradiol-17β, and progesterone production in human granulosa cells, whereas melatonin ameliorated these phenotypes. Next, we found that the protective effect of melatonin against apoptosis was via reducing ER stress because the inhibition of ER stress displayed similar protective effects during DON treatment. Moreover, melatonin provided no additional protection when ER stress was inhibited. We further found that FOXO1 is a pivotal downstream effector of melatonin and ER stress in regulating DON-induced apoptosis in human granulosa cells. Blocking of FOXO1 reduced DON-induced cells death and FOXO1 activation could be suppressed by melatonin or ER stress inhibitor. However, melatonin failed to further restore cells viability in the presence of FOXO1 inhibitor. Collectively, our results reveal a new mechanism of melatonin in protecting against DON-induced apoptosis and dysfunction by suppressing ER stress and FOXO1 in human granulosa cells.

Rufeng Xue

Shuhang Li

Huijuan Zou

Dongmei Ji

Mingrong Lv

Ping Zhou

Zhaolian Wei

Zhiguo Zhang

Yunxia Cao

Melatonin alleviates deoxynivalenol-induced apoptosis of human granulosa cells by reducing mutually accentuated FOXO1 and ER stress

褪黑素通过减少相互增强的FOXO1和内质网应激缓解脱氧雪腐镰刀菌烯醇诱导的人类卵泡颗粒细胞凋亡

Abstract The redox state of thiol groups derived from cysteine residues in proteins regulates cellular functions. Changes in the redox state of thiol groups in the epididymis are involved in sperm maturation. Furthermore, the redox state of thiol groups in proteins changes during the process of sperm capacitation. However, the effect of the redox state of thiol groups in sperm membrane proteins on the fertilization ability of sperm has not been studied. Therefore, in this study, we oxidized thiol groups in sperm membrane proteins using 5,5-dithiobis-(2-nitrobenzoic acid) (DTNB), which is a thiol-selective oxidizing agent, and examined the effect of oxidation of these thiol groups on the fertilization ability of sperm. Oocytes and sperm were obtained from C57BL/6 J mice, and Jcl:ICR mice were used as recipients for embryo transfer. Oxidation of the thiol groups by DTNB decreased the in vitro fertilization rate, and removal of the zona pellucida recovered the fertilization rate. DTNB treatment decreased the amplitude of the lateral head, which is an indicator of hyperactivation, and suppressed an increase in the intracellular calcium ion concentration, which is essential for hyperactivation. These findings suggest that oxidation of thiol groups in sperm membrane proteins can decrease the fertility of sperm by suppressing calcium ion influx and hyperactivation.

Satohiro Nakao

Kazuki Shirakado

Kana Tamura

Reiri Koga

Mayumi Ikeda-Imafuku

Yu Ishima

Naomi Nakagata

Toru Takeo

Oxidation of thiol groups in membrane proteins inhibits the fertilization ability and motility of sperm by suppressing calcium influx

膜蛋白中巯基的氧化通过抑制钙内流抑制精子的受精能力和运动能力

Abstract Uterine infections cause ovarian dysfunction and infertility. The bacterial endotoxin, lipopolysaccharide (LPS), accumulates in the follicular fluid of dominant follicles of cows with uterine infections. Granulosa cells produce an innate inflammatory response to LPS, altering the follicular microenvironment of the oocyte. We hypothesized that developmental competence and embryo quality would be reduced when oocytes are matured in an inflammatory environment. Bovine mural granulosa cells were exposed to either 1 μg/mL of LPS or medium alone for 24 h to produce conditioned medium. Inflammatory responses of mural granulosa cells were confirmed by increased expression of CXCL8, IL1B, IL6 and TNF. Bovine cumulus-oocyte complexes were matured for 22 ± 1 h in medium supplemented with either 1 μg/mL of LPS, 10% v/v conditioned medium of granulosa cells treated with either LPS (LCM) or medium alone (CCM), or no supplementation (CON). In addition, polymyxin B (20 μg/mL) was added to maturation medium to sequester LPS. Following maturation, cumulus-oocyte complexes were fertilized and cultured for 7.5 days with no further treatment. Oocyte maturation using LPS or LCM impaired development to the blastocysts stage, reduced the number of total and CDX2 negative blastomeres and increased TUNEL positive cells in blastocysts. Polymyxin B could rescue these effects in the LPS group but not in the LCM group, indicating factors produced by granulosa cells and not LPS alone compromised oocyte development. These findings suggest that the inflammatory milieu produced by granulosa cells in response to LPS impairs oocyte competence and quality of resultant blastocyst-stage embryos.

Arslan Tariq

Zachary K Seekford

John J Bromfield

Inflammation during oocyte maturation reduces developmental competence and increases apoptosis in blastocysts

卵母细胞成熟过程中炎症反应降低胚胎发育能力并增加囊胚凋亡

Di(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer known for its toxic effects on the male reproductive system. Green tea polyphenols (GTPs), recognized for their antioxidant and anti-inflammatory properties, have demonstrated protective effects on various organs, but the mechanisms by which GTPs mitigate DEHP-induced testicular damage remain unclear.

Heng Shi

Xin-Hai Zhao

Qin Peng

Xian-Ling Zhou

Si-Si Liu

Chuan-Chuan Sun

Qiu-Yu Cao

Shi-Ping Zhu

Sheng-Yun Sun

Green tea polyphenols alleviate di (2-ethylhexyl) phthalate-induced testicular injury in mice via lncRNA–miRNA–mRNA axis

绿茶多酚通过lncRNA–miRNA–mRNA轴减轻二(2-乙基己基)邻苯二甲酸酯诱导的小鼠睾丸损伤

Abstract The embryonic diapause of the giant panda (Ailuropoda melanoleuca) has caused great difficulties in monitoring pregnancy in this vulnerable species. The secretion of prolactin (PRL) from anterior pituitary glandular lactotropic cells is an important signal for the termination of embryonic dormancy. Currently, the mechanism by which PRL affects embryonic diapause in giant pandas and methods for detecting PRL in this species are poorly understood. In this study, the first sandwich enzyme immunoassay for detecting PRL in giant panda urine was established by using two anti-giant panda PRL antibodies prepared as coating and labeling antibodies, and PRL recombinant proteins prepared via the prokaryotic system as standards. The established method was used to detect the levels of PRL in the urine of giant pandas during pregnancy. At the same time, the changes in PRL levels in giant pandas and with the relationship between PRL and progestagen levels was analyzed during the luteal phase. The results showed that in female giant pandas, PRL levels significantly increased before the progestagen peak, and during the luteal phase, the PRL level was significantly greater in giant pandas that gave birth than in those that did not give birth and those in the non-estrus group. To the best of our knowledge, this is the first study to preliminarily explore the mode of action of PRL in the gestation period of giant pandas, and lays a foundation for further study of the regulatory mechanisms of endocrine hormones in the giant panda.

Wang Shenfei

Zhang Mengshi

Li Feiping

Hu Xianbiao

Li Yan

Wang Juan

Liu Xiangyu

Hou Rong

Liu Yuliang

Kailai Cai

Preliminary urinary profiles of prolactin during gestation and the synergistic effects of embryonic diapause hormones in the giant panda (<i>Ailuropoda melanoleuca</i>)

妊娠期间催乳素的初步尿液特征及胚胎滞育激素在大熊猫（<i>Ailuropoda melanoleuca</i>）中的协同效应

Abstract Developing embryos are susceptible to fluctuations in the nutrients and metabolites concentrations within the reproductive tract, which can lead to alterations in their developmental trajectory. Ketotic dairy cows have diminished fertility, and elevated levels of the ketone body beta-hydroxybutyrate (BHB) have been associated with poor embryonic development. We used an in vitro model based on either in vitro fertilization (IVF) or parthenogenesis to investigate the effects of BHB on the preimplantation bovine embryo development, epigenome, and transcriptome. Embryo culture medium was supplemented with BHB at a similar concentration to that present in the blood of cows suffering with severe ketosis, followed by analysis of blastocysts formation rate, diameter, total number of cells, levels of H3K9 beta-hydroxybutyrylation (H3K9bhb), apoptosis, and transcriptional alterations. As a result, we observed that BHB reduced the blastocysts rates, the diameter and the total number of cells in both parthenotes and IVF embryos. Exposure to BHB for either 3 or 7 days greatly increased the H3K9bhb levels in parthenotes at the 8-cells and blastocyst stages, and affected the expression of HDAC1, TET1, DNMT1, KDM6B, NANOG, and MTHFD2 genes. Additionally, culture of IVF embryos with BHB for 7 days dramatically increased H3K9bhb and reduced NANOG in blastocysts. RNA-seq analysis of IVF blastocysts revealed that BHB modulated the expression of 118 genes, which were involved with biological processes such as embryonic development, implantation, reproduction, proliferation, and metabolism. These findings provided valuable insights into the mechanisms through which BHB disrupts preimplantation embryonic development and affects the fertility in dairy cows.

Juliano Rodrigues Sangalli

Ricardo Perecin Nociti

Marcos Roberto Chiaratti

Alessandra Bridi

Ramon Cesar Botigelli

Dewison Ricardo Ambrizi

Helena Fabiana Reis de Almeida Saraiva

Felipe Perecin

Juliano Coelho da Silveira

Pablo Juan Ross

Flávio Vieira Meirelles

Beta-hydroxybutyrate alters bovine preimplantation embryo development through transcriptional and epigenetic mechanisms

β-羟基丁酸通过转录和表观遗传机制改变牛植入前胚胎发育

Abbreviation	Biol. Reprod.
Journal Impact	3.20
Quartiles(Global)	REPRODUCTIVE BIOLOGY(Q2)

ISSN	0006-3363, 1529-7268
h-index	203

Publication Information	Publisher: Oxford University Press，Publishing cycle: Monthly，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 1969，Proportion of original research papers: 84.72%，Self Citation Rate:3.20%， Gold OA Rate: 16.08%
Average review cycle	网友分享经验：平均1月
Average recruitment ratio	网友分享经验：约75%

Biology of Reproduction

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