Estrogen signaling in testicular cells

International Symposium on Cell SignalingInternational audienceAromatase transforms irreversibly androgens into estrogens and is present in the endoplasmic reticulum of various tissues including the mammalian testis. In rat all testicular cells except peritubular cells express aromatase. Indeed in adult rat germ cells (pachytene spermatocytes and round spermatids) we have demonstrated the presence of a functional aromatase (transcript, protein and biological activity) and the estrogen output is equivalent to that of Leydig cells. In addition in the adult rat, transcripts of aromatase vary according to the germ cell type and to the stages of seminiferous epithelium. By contrast with the androgen receptors mainly localized in somatic cells, estrogen receptors (ERs) are described in most of the testicular cells including germ cells. Moreover, besides the presence of high affinity ERα and/or ERβ, a rapid membrane effect has been recently reported and we demonstrated that GPR30 (a transmembrane intracellular estrogen receptor) is expressed in adult rat pachytene spermatocytes. Therefore estrogens through both GPR30 and ERα are able to activate the rapid EGFR/ERK/c-jun signaling cascade, which in turn triggers an apoptotic mitochondrial pathway involving an increase in Bax expression and a concomitant reduction of cyclin A1 and B1 gene levels. In another study in round spermatids of adult rat we have shown that the rapid membrane effect of estradiol is also efficient in controlling apoptosis and maturation / differentiation of these haploid germ cells. In man the presence of a biologically active aromatase and of estrogen receptors has been reported in Leydig cells, but also in immature germ cells and ejaculated spermatozoa. Thus the role of estrogen (intracrine, autocrine and / or paracrine) in spermatogenesis (proliferation, apoptosis, survival and maturation) and more generally, in male reproduction is now evidenced taking into account the simultaneous presence of a biologically active aromatase and the widespread distribution of estrogen receptors especially in haploid germ cells

Maternal parity affects placental development, growth and metabolism of foals until 1 year and a half

International audiencePrimiparous mares are known to produce smaller foals than multiparous mares. This difference seems to be partly explained by the reduced exchange surface and volume of the placental villi in primiparous compared to multiparous placentas. The effect of maternal parity on foals' post-natal growth, metabolism and sexual maturation, however, has been given little consideration. The objectives of this work were to analyse placental biometry and structure at term, growth of foals and yearlings, their metabolism and testicular maturation at one year of age. Twenty multiparous mares (M), aged over 6 years and 12 primiparous mares (P), aged up to 5 years were artificially inseminated with the same stallion and monitored the same way until foaling. At birth, foals and placentas were measured and placentas were sampled above at the umbilical cord insertion, as well as in the pregnant and the non-pregnant horn to perform stereological analyses. Foals were weighed and measured until 540 days of age. At 120 and 360 days of age, an Intravenous Glucose Tolerance Test was performed on foals and yearlings. At 360 days of age, the males were castrated and testicular maturation analysed by RT-qPCR. At birth, P dams produced lighter and smaller foals and placentas. The foal birth weight to placental surface ratio was lower in the P compared to the M group. P Foals remained lighter than M foals until 360 days of age and smaller until at least 540 days of age. At 120 days of age, P foals had a higher glucose tolerance than M foals, and then may be less mature than M foals in terms of the control of their glucose homeostasis. At 360 days of age, the testicles of prepubertal P stallions were less mature in the P vs the M group. In conclusion, primiparous dams produce intrauterine growth restricted, less mature and smaller foals compared to multiparous dams with altered metabolism and growth until at least 540 days of age. These differences could affect the sport career of these foals, especially if it begins at an early age

Number (and percentage) of osteochondrosis (OC) negative and positive Normal (n = 10) and Obese (n = 14) foals and yearlings at 6, 12 and 18 months.

<p>The proportion of OC-positive foals and yearlings was not different at 6 and 18 months between groups but there were more OC-positive O yearlings at 12 months compared to N yearlings (p = 0.03).</p

Daily nutritional information (median and IQR) of feed distributed to Normal (N) and Obese (O) broodmares from wintering at 180 days of gestation until foaling.

<p>There are no significant differences between groups. Net energy (A), horse digestible crude proteins (B), raw cellulose (C), and calcium to phosphorus ratio (D). BW: bodyweight.</p

Plasma Serum amyloid A concentrations in Normal (n = 10) and Obese (n = 14) foals and yearling from birth to 12 months of age.

<p>For each time point, asterisks indicate a significant difference between groups (p<0.05).</p

Experimental design.

<p>(A)The year before insemination, the body condition score of barren mares was monitored. Normal (N, n = 10) mares had a fluctuant body condition score relevant to the nutrient availability whereas Obese (O, n = 14) mares had a high and stable body condition during the year. (B)From insemination until 6 months of gestation, pregnant mares were pastured as one same herd in the same pasture. From the 6th month of gestation, they were housed in individual boxes and fed the same amount of energy, proteins, fibre, calcium and phosphorus according to body weight until foaling. (C)From 3 days until 6 months of age, foals were kept in pasture with their dam. They were weaned by abrupt separation at 6 months, housed in open barns and fed the same amount of feed, following the French recommendations for growing foals [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0190309#pone.0190309.ref049" target="_blank">49</a>]. Colts were castrated at 12 months as a routine procedure. From 12 to 18 months of age, all yearlings pastured in the same pasture. A.I.: Artificial insemination, BCS: body condition score.</p

Indexes calculated with the Bergman’s minimal model (median and IQR): Acute insulin response to glucose (AIRg), insulin sensitivity (IS), disposition index (DI) and glucose effectiveness (Sg), basal plasma glucose (GB) and basal plasma insulin (IB) in Normal (n = 10) and Obese (n = 14) mares at 300 days of gestation.

<p>Indexes calculated with the Bergman’s minimal model (median and IQR): Acute insulin response to glucose (AIRg), insulin sensitivity (IS), disposition index (DI) and glucose effectiveness (Sg), basal plasma glucose (GB) and basal plasma insulin (IB) in Normal (n = 10) and Obese (n = 14) mares at 300 days of gestation.</p

Primers sequences used for amplification of equine products in RT-qPCR assays in testicles of prepubertal stallions.

<p>Primers sequences used for amplification of equine products in RT-qPCR assays in testicles of prepubertal stallions.</p

Indexes calculated with the Bergman’s minimal model (median and IQR): Acute insulin response to glucose (AIRg), insulin sensitivity (SI), disposition index (DI) and glucose effectiveness (Sg), basal plasma glucose (GB) and basal plasma insulin (IB) in Normal (n = 10) and Obese (n = 14) foals and yearlings at 6, 12 and 18 months of age.

<p>Indexes calculated with the Bergman’s minimal model (median and IQR): Acute insulin response to glucose (AIRg), insulin sensitivity (SI), disposition index (DI) and glucose effectiveness (Sg), basal plasma glucose (GB) and basal plasma insulin (IB) in Normal (n = 10) and Obese (n = 14) foals and yearlings at 6, 12 and 18 months of age.</p