17 -Estradiol and environmental estrogens significantly affect mammalian sperm function

Adeoya-Osiguwa, Susan; Markoulaki, Styliani; Pocock, Victoria; Milligan, S. R.; Fraser, Lynn R.

doi:10.1093/humrep/deg037

Cited by 155 publications

(134 citation statements)

References 40 publications

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“…These data are consistent with the results of the western blot analysis, where a reduced expression of both AR isoforms was observed, and with recent data reported by Zalata et al (2013). A functional role for steroid receptors in capacitation, acrosome reaction, motility, and survival in sperm has been reported (Adeoya-Osiguwa et al 2003). It is well known that human ejaculated sperm are not capable of fertilizing oocyte as they need two important sequential steps: capacitation and acrosome reaction.…”

Section: Discussionsupporting

confidence: 92%

Human sperm anatomy and endocrinology in varicocele: role of androgen receptor

Guido¹,

Santoro²,

Amicis³

et al. 2014

Reproduction

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The study of androgens involved in male reproduction has been object of intense efforts, while their reported action on human male gametes is limited. We previously described the presence of androgen receptor (AR) in sperm with a role related to the modulation of the PI3K pathway. In the present study, we investigated the expression of AR and its ultrastructural location in normal sperm as well as in spermatozoa obtained from varicocele patients. We observed a reduced AR content in varicocele sperm with respect to healthy sperm by western blot analysis and transmission electron microscopy (TEM). The ultrastructural location of AR was detected mainly on the head membrane as well as in the nucleus, neck, and mitochondria. Influence of dihydrotestosterone (DHT) treatment on cholesterol efflux was increased in normal sperm, while it was reduced or absent in varicocele sperm. To better understand DHT/AR significance in human male gametes, we evaluated triglyceride content and lipase, acyl-CoA dehydrogenase, and glucose-6-phosphate dehydrogenase activities upon DHT treatment. The metabolic outcome glimpsed in normal sperm was an increased metabolic rate, while 'varicocele' sperm economized energy. Taken together, our results reveal DHT and AR as new players in sperm endocrinology, indicating that varicocele sperm may have difficulty in switching to the capacitated status. A decreased AR expression and a consequent reduced responsiveness to DHT in sperm may represent molecular mechanisms involved in the pathophysiology of varicocele leading to male infertility. This study revealed new detrimental effects of varicocele on sperm at the molecular level.

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Section: Discussionsupporting

confidence: 92%

Human sperm anatomy and endocrinology in varicocele: role of androgen receptor

Guido¹,

Santoro²,

Amicis³

et al. 2014

Reproduction

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“…On the other hand, the concentration of estrogen in ovarian fluid is much higher when compared with the plasma (Free & Jaffe 1979, Hess et al 1995 and it reaches multiple values depending on the time of the estrus fluctuating between 145 and 2100 pg/ml in rats and mice (Shaikh 1971). Most of our knowledge regarding these processes has been obtained from in vitro studies (Adeoya-Osiguwa et al 2003, Ded et al 2010, Sebkova et al 2012, and for this reason it is really important to also do in vivo experiments.…”

Section: Introductionmentioning

confidence: 99%

In vivo exposure to 17β-estradiol triggers premature sperm capacitation in cauda epididymis

Děd¹,

Šebková²,

Černá³

et al. 2013

Reproduction

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Estrogens play a crucial role in spermatogenesis and estrogen receptor a knock-out male mice are infertile. It has been demonstrated that estrogens significantly increase the speed of capacitation in vitro; however this may lead to the reduction of reproductive potential due to the decreased ability of these sperm to undergo the acrosome reaction. To date the in vivo effect of estrogens on the ability of sperm to capacitate has not been investigated. Therefore, in this study, we exposed mice (nZ24) to 17b-estradiol (E 2 ) at the concentration of 20 ng/ml either during puberty from the fourth to seventh week of age (nZ8), or continuously from birth for a period of 12 weeks (nZ8) at which age the animals from both groups were killed. The capacitation status of epididymal and testicular sperm was analysed by tyrosine phosphorylation (TyrP) antibody (immunofluorescence and western blot) and chlortetracycline (CTC) assay. According to our results, in vivo exposure to increased E 2 concentrations caused premature sperm capacitation in the epididymis. The effect of E 2 , however, seems reversible because after the termination of the exposure premature epididymal sperm capacitation is decreased in animals treated during puberty. Furthermore the changes in epididymal sperm capacitation status detected by TyrP and CTC positively correlate with plasma levels of E 2 and the expression of the estrogen-dependent trefoil factor 1 (Tff1) gene in testicular tissue. Therefore, our data implicate that in vivo exposure to E 2 under specific conditions leads to the premature capacitation of mouse sperm in epididymis with a potential negative impact on the sperm reproductive fitness in the female reproductive tract.

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“…It has been demonstrated previously that oestradiol increased motility, oxidative metabolism, longevity of spermatozoa and oocyte penetration (Idaomar et al 1989). Recently, it has been shown that oestradiol and phytoestrogens improve mouse sperm capacitation (Adeoya-Osiguwa et al 2003). Thus oestrogens may act via a membrane oestrogen-binding protein, to exert a rapid effect.…”

Section: Discussionmentioning

confidence: 98%

Human immature germ cells and ejaculated spermatozoa contain aromatase and oestrogen receptors

Lambard¹,

Galeraud-Denis²,

Saunders³

et al. 2004

Journal of Molecular Endocrinology

122

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It is now well established that oestrogens play a part in germ cell function. These hormones are synthesised by the cytochrome P450 aromatase (P450 arom) and act via two kinds of receptor (ER and ER ). Although the presence of aromatase and oestrogen receptors in mammalian testis is now well documented, the localisation of these proteins in human germ cells is not yet clear. The primary purpose of the current study was to look for the expression of aromatase and oestrogen receptors in human germ cells. Human immature germ cells were collected from semen samples with an excess of rounds cells (>20%) and purified spermatozoa were obtained after sedimentation on a discontinuous PureSperm gradient. Expression of aromatase and oestrogen receptors was determined by RT-PCR with specific primers, and by Western blot using monoclonal antibodies. RT-PCR products for aromatase, ER and ER were amplified from total RNA isolated from human germ cells and spermatozoa. We identified an ER isoform variant that lacks exon 4 in human germ cells and visualised P450 arom as a single band of 49 kDa in germ cells, as we have already reported for human ejaculated spermatozoa. By Western blot, we identified two proteins for ER at ∼ 50 and ∼ 60 kDa, which could correspond to the long and short forms of ER formed from the use of alternative start sites. In human ejaculated spermatozoa, ER protein was not detected, even though we could amplify mRNA. Using Western blot analysis and a monoclonal antibody specific for ER , we detected two proteins in human immature germ cells: one of the expected size (66 kDa) and a second one of 46 kDa. In mature spermatozoa, only the 46 kDa band was observed and we speculate it may be related to the ER isoform lacking exon I. In conclusion, we have identified P450 arom and ER proteins (full-length and variant) in human germ cells. Further studies are now required to elucidate the mechanism of action of oestrogens on human male germ cells, in terms of both genomic and 'non-genomic' pathways.

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17 -Estradiol and environmental estrogens significantly affect mammalian sperm function

Cited by 155 publications

References 40 publications

Human sperm anatomy and endocrinology in varicocele: role of androgen receptor

Human sperm anatomy and endocrinology in varicocele: role of androgen receptor

In vivo exposure to 17β-estradiol triggers premature sperm capacitation in cauda epididymis

Human immature germ cells and ejaculated spermatozoa contain aromatase and oestrogen receptors

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