Functional and Proteomic Alterations of F1 Capacitated Spermatozoa of Adult Mice Following Gestational Exposure to Bisphenol A

Rahman, Md Saidur,Kwon, Woo-Sung,Ryu, Do-Yeal,Khatun, Amena,Karmakar, Polash Chandra,Ryu, Buom-Yong,Pang, Myung-Geol American Chemical Society 2018 JOURNAL OF PROTEOME RESEARCH Vol.17 No.1

<P>Studies regarding bisphenol A (BPA) exposure and male (in)fertility have conventionally focused on modifications in ejaculated spermatozoa function from exposed individuals. However, mammalian spermatozoa are incapable of fertilization prior to achieving capacitation, the penultimate step in maturation. Therefore, it is necessary to investigate BPA-induced changes in capacitated spermatozoa and assess the consequences on subsequent fertilization. Here, we demonstrate the effect of gestational BPA exposure (50 μg/kg bw/day, 5 mg/kg bw/day, and 50 mg/kg bw/day) on the functions, biochemical properties, and proteomic profiles of F1 capacitated spermatozoa from adult mice. The data showed that high concentrations of BPA inhibited motility, motion kinematics, and capacitation of spermatozoa, perhaps because of increased lipid peroxidation and protein tyrosine nitration, and decreased intracellular ATP levels and protein kinase-A activity in spermatozoa. We also found that BPA compromised the rates of fertilization and early embryonic development. Differentially expressed proteins identified between BPA-exposed and control groups play a critical role in energy metabolism, stress responses, and fertility. Protein function abnormalities were responsible for the development of several diseases according to bioinformatics analysis. On the basis of these results, gestational exposure to BPA may alter capacitated spermatozoa function and the proteomic profile, ultimately affecting their fertility potential.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jprobs/2018/jprobs.2018.17.issue-1/acs.jproteome.7b00668/production/images/medium/pr-2017-00668k_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/pr7b00668'>ACS Electronic Supporting Info</A></P>

Calcium Influx and Male Fertility in the Context of the Sperm Proteome: An Update

Rahman, Md Saidur,Kwon, Woo-Sung,Pang, Myung-Geol Hindawi Publishing Corporation 2014 BioMed research international Vol.2014 No.-

<P>Freshly ejaculated spermatozoa are incapable or poorly capable of fertilizing an oocyte. The fertilization aptness of spermatozoa depends on the appropriate and time-dependent acquisition of hyperactivation, chemotaxis, capacitation, and the acrosome reaction, where calcium (Ca<SUP>2+</SUP>) is extensively involved in almost every step. A literature review showed that several ion channel proteins are likely responsible for regulation of the Ca<SUP>2+</SUP> uptake in spermatozoa. Therefore, manipulation of the functions of channel proteins is closely related to Ca<SUP>2+</SUP> influx, ultimately affecting male fertility. Recently, it has been shown that, together with different physiological stimuli, protein-protein interaction also modifies the Ca<SUP>2+</SUP> influx mechanism in spermatozoa. Modern proteomic analyses have identified several sperm proteins, and, therefore, these findings might provide further insight into understanding the Ca<SUP>2+</SUP> influx, protein functions, and regulation of fertility. The objective of this review was to synthesize the published findings on the Ca<SUP>2+</SUP> influx mechanism in mammalian spermatozoa and its implications for the regulation of male fertility in the context of sperm proteins. Finally, Pathway Studio (9.0) was used to catalog the sperm proteins that regulate the Ca<SUP>2+</SUP> influx signaling by using the information available from the PubMed database following a MedScan Reader (5.0) search.</P>

Application of Ultrasonography to Investigate Postpartum Anestrus in Water Buffaloes

Rahman, Md Saidur,Shohag, Abu Said,Kamal, Md. Mostafa,Parveen, Nasreen,Shamsuddin, Mohammed The Korean Society of Animal Reproduction 2012 Reproductive & developmental biology Vol.36 No.2

Anestrus is one of the most important production limiting disorders in dairy buffaloes and its underlying causes have been a current topic of studies. The objectives of this study were to explore the causes of anestrus in buffaloes with the application of ultrasonography. Two examinations were performed by transrectal ultrasonography at 12 days apart in buffalo cows that were not seen in oestrus at 60 or more days postpartum. As high as 54.5% buffaloes had silent ovulation and 45.5% suffered from the true anestrus with ovarian dysfunction. The duration of anestrus after calving was 60~90, 91~120, 121~180 and 181~365 days in 27%, 32%, 18% and 23% buffalo cows, respectively. Treatment with prostaglandin of cyclic buffalo cows with a corpus luteum (72.7%) resulted in higher estrous rate as compared with close observation of estrus (23.1%) by the farmer (p=0.021). Acyclic buffalo cows without any corpus luteum on ovaries were successfully treated with gonadotropin releasing hormone (70%), resulting in higher estrous detection rate than those treated with a vitamin-mineral mixture (20%) (p=0.035). In conclusion, poor heat detection due to silent ovulation is the most important cause of apparent anoestrus in buffaloes; however the percentage of the true anestrous is also quite high in postpartum buffaloes.

Understanding the molecular mechanisms of bisphenol A action in spermatozoa

Rahman, Md Saidur,Pang, Myung-Geol The Korean Society for Reproductive Medicine 2019 Clinical and Experimental Reproductive Medicine Vol.46 No.3

Bisphenol A (BPA) is an endocrine-disrupting chemical that is capable of interfering with the normal function of the endocrine system in the body. Exposure to this chemical from BPA-containing materials and the environment is associated with deleterious health effects, including male reproductive abnormalities. A search of the literature demonstrated that BPA, as a toxicant, directly affects the cellular oxidative stress response machinery. Because of its hormone-like properties, it can also bind with specific receptors in target cells. Therefore, the tissue-specific effects of BPA mostly depend on its endocrine-disrupting capabilities and the expression of those particular receptors in target cells. Although studies have shown the possible mechanisms of BPA action in various cell types, a clear consensus has yet to be established. In this review, we summarize the mechanisms of BPA action in spermatozoa by compiling existing information in the literature.

Bioinformatics Annotation of Human X and Y Chromosome-Encoded Proteins associated to Immune Functions

Md Saidur Rahman,Woo-Sung Kwon,Myung-Geol Pang 한국동물생명공학회(구 한국동물번식학회) 2017 발생공학 국제심포지엄 및 학술대회 Vol.2017 No.10

Even human genome has been sequenced completely, we have very limited idea of all characterized genes at the protein level. Therefore, several attempts have been taken to map proteome of human chromosome. Since sex chromosomes determined the sex of individual, it important to study sex chromosome-encoded proteins. Here, we studied human sex chromosome- encoded proteins of the immune system, protein pathways, protein-protein interactions, and diseases association using several bioinformatics tools. We retrieved 30 proteins (X chromosome 28; Y chromosome 7; both 5) from the recent NCBI human genome annotation, based on their association with immune systems (immunological and inflammation pathways) by Pathway studio program. Searching of these proteins in the Human Proteome Project, including neXtProt, PeptideAtlas, and the Human Protein Atlas showed that all proteins were also identified in several cells and tissues of body. Proteins were further investigated using Pathway Studio and STRING programs. Pathway Studio and STRING programs showed 15 and 25 X chromosome-encoded proteins were interacted. All Y chromosome-encoded proteins showed interactions using STRING program, however no interaction was found using Pathway studio. In addition, difference in human sex chromosome-encoded proteins of the immune system showed an indirect relationship with the occurrence of some diseases in a sex specific manner.

The Transgenerational Significance of Bisphenol‒A on Sperm Function and Fertility of CD-1 Male Mice

Md Saidur Rahman,Won-Ki Pang,Ki-Uk Kim,Ye-Ji Kim,Do-Yeal Ryu,Amena Khatun,Sung-Jae Yoon,Woo-Sung Kwon,Myung-Geol Pang 한국수정란이식학회 2016 한국수정란이식학회 학술대회 Vol.2016 No.10

Bisphenol‒A (BPA) is a known endocrine‒disrupting chemical used extensively to manufacture plastic bottles, canned food linings, thermal receipts, and other commonly used items. BPA is capable of inducing chromosomal alterations in germ cell line, thereby produced transgenerational effects on brain function, social recognition, reproductive diseases, sperm quality, gene expression, and obesity. Here, we aimed to investigate the transgenerational effects of BPA on murine male fertility. Six-week-old male mice (F0) were gavaged with corn oil (control), two different doses of BPA (5 mg, and 50 mg·kg bw-1·day-1),andethinylestradiol(EE,0.4mg·kg bw-1·day-1), dailyfor6weeks. Treated male mice were mated with wild‒type female and sibling pairs were bred up to the third generation (F3) in a similar manner with no further BPA exposure. Testes and spermatozoa were collected from 14-week-old males of all generation (F0 to F3) to evaluate testis weight, sperm function, and fertility. We found that high concentration of BPA significantly increased testicular weight in F2. Although the sperm viability, capacitation status, and intracellular ROS levels were not affected by BPA, however, sperm count, motility, hyperactivated motility, and intracellular ATP levels were significantly altered by BPA, dose dependently. In majority of the cases the effects were prominent in F2 followed by F1 and F0, whereas the effects were diminished in F3 generation. Simultaneously, high concentration of BPA significantly decreased cleavage and blastocyst formation rate in both F1 and F2. Similar inhibitory effects on cleavage and blastocyst were also noted in F1 by low dose of BPA. Depending on these findings we conclude that BPA decreases the fertility potential of exposed males and has an adverse impact on sperm function and fertility in subsequent generations.

Alterations of Male Fertility following Exposure to Bisphenol A

Md Saidur Rahman 한국수정란이식학회 2018 한국수정란이식학회 학술대회 Vol.2018 No.11

Bisphenol A (BPA) is a common industrial chemical that has been used extensively to make certain plastics and resins since the 1960s. As a potential endocrine disruptors, BPA has been investigated for its impact on fertility/reproduction in animals and humans. However, the molecular mechanisms of BPA action and standard method for detecting BPA-related health hazards are unclear. Considering in-vitro experimental model, we investigated the effects of BPA (0.0001 to 100 μM) exposure on mouse spermatozoa. We revealed that BPA affects several sperm functions by triggering the mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and protein kinase-A (PKA) activity. High doses of this chemical was also likely for the activation of protein tyrosine phosphorylation in a PKA-dependent signaling consequently induced a precocious acrosome reaction. Simultaneously, BPA has been found to decrease the rate of fertilization and early embryonic development. In addition, BPA induced differential protein expression in spermatozoa were responsible for the pathogenesis of many diseases. Considering in vivo experimental model, we deliberate the effects of gestational BPA exposure (TDI, NOAEL, and LOAEL doses) on both ejaculated and capacitated spermatozoa in F1 adult mice. We confirmed that BPA affects several sperm function in F1 male. These effects appeared to be caused by reduced numbers of stage VIII seminiferous epithelial cells in testis and decreased PKA activity and tyrosine phosphorylation (non-capacitated) in spermatozoa. We also noticed that BPA decreased average litter size as well as compromise the rates of cleavage and blastocyst formation. Proteins differentially expressed in both capacitated/ejaculated spermatozoa play a critical role in energy metabolism, stress responses, and fertility, finally predispose to the development of several diseases. On the basis of these results, we suggest that BPA alter spermatozoa function and the proteomic profile, ultimately affecting their fertility potential. Therefore, it is of critical public health significance to reevaluate the levels of BPA exposure that are currently deemed to be acceptable.

The Transgenerational Significance of Bisphenol‒A on Sperm Function and Fertility of CD-1 Male Mice

Md Saidur Rahman,Won-Ki Pang,Ki-Uk Kim,Ye-Ji Kim,Do-Yeal Ryu,Amena Khatun,Sung-Jae Yoon,Woo-Sung Kwon,Myung-Geol Pang 한국동물생명공학회(구 한국동물번식학회) 2016 발생공학 국제심포지엄 및 학술대회 Vol.2016 No.10

소,쥐,되지 정자의 에스트로겐 물질에 대한 민감도

( Md Saidur Rahman ),류도열 ( Do Yeal Ryu ),김예지 ( Ye Ji Kim ),이준섭 ( June Sub Lee ),권우성 ( Woo Sung Kwon ),윤성재 ( Sung Jae Yoon ),방명걸 ( Myung Geol Pang ) 한국축산학회 2014 축산기술과 산업 Vol.5 No.3

본 연구는 에스트로켄 물질 [17 β-estradiol(E2), progesterone(P4), genistein(GEN), 4-tert-octylphenol(OP)]이포유동물 (소, 돼지, 생쥐) 정자의 수정능력 획득과 첨체반응 민감도에 미치는 영향을 체외에서 확인하기 위해 실시하였다. E2, P4, GEN, OP(0.001-100㎛)를 15분 또는 30분 동안 5% CO₂, 39℃에서 배양 후 수정능력 획득 및 첨체반응 여부를 확인하기 위하여 Hoechst 33258/Chlortetracycline 염색법을 실시하였다. E2는 15분 및 30분 처리시 생쥐 정자에서 농도에 따라 첨체반응을 유의적으로 증가시켰다(p<0.05). 돼지 정자의 경우는 15분 처리시 가장 낮은 농도(0. 001㎛)의 처리구에서만 수정능력 획득을 유의적으로 증가 시켰고, 30분 처리시 농도에 따라 첨체반응을 유의적으로 증가시켰다(p<0.05). P4는 15분 처리시 소와 생쥐의 정자에서 농도에 따라 첨체반응을 유의적으로 증가시켰다고, 돼지의 경우 농도에 따라 수정능력 획득을 유의적으로 즌가시켰다(p<0.05). 또한, 30분 동안 처리한 생쥐 정자의 농도에 따라 수정능력 획득을 유의적으로 증가시켰다(p<0.05). GEN 은 15분과 30분동안 배양한 돼지 정자와 30분 동안 배양한 생쥐정자의 쳄체반응을 농도에 따라 유의적으로 증가시켰다(p<0.05). OP의 경우 15분 처리시 생쥐정자의 첨체반응을 농도에 따라 유의적으로 증가시켰다(p<0.05). 특히 이들 물질 중 E2 와 P4에 대한 민감도 더 높아 효과적으로 정자의 기능에 영향을 주는 것으로 확인되었다. 본 연구를 종합해 보면 에스트로겐 물질은 소, 돼지, 생쥐의 정자에서 수정능력 획득과 첨체반응을 효과적으로 야기시켰으며 이들 물질에 대한 민감도 차이는 종간에 유의적 차이가 있었다. 이러한 민감도 민감도 차이를 이용하여 정자를 이용한 저농도의 내분비계교란문질 탐색이 가능할 것으로 기대된다.

Sodium Nitroprusside Induce Phosphorylation of Ferritin Light Chain Protein, Regulates the Acrosome Reaction and Fertility of Mice Spermatozoa

Md Saidur Rahman,Won-Ki Pang,Ye-Ji Kim,Do-Yeol Ryu,Amena Khatun,Sung-Jae Yoon,Woo-Sung Kwon,Myung-Geol Pang 한국동물생명공학회(구 한국동물번식학회) 2015 발생공학 국제심포지엄 및 학술대회 Vol.2015 No.10