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Short-acting testosterone appears to have lesser effect on male reproductive potential compared to long-acting testosterone in mice.

ABSTRACT: Objective:To compare the effect of exogenous short-acting and long-acting testosterone on male reproductive potential in mice. Design:In vivo mouse model. Setting:University-based basic science research laboratory. Animals:A total of 30 wild-type C57BL/6 male and female mice were used for this experimentation. The male mice were used for control group and testosterone supplementation, while both male and female mice were used for the breeding portion of the study. Interventions:Exogenous testosterone was administered either in short-acting formulation (Monday-Wednesday-Friday dosing schedule, testosterone propionate 0.2 mg/kg), or long-acting formulation (3-month dosing schedule - testosterone pellets 150 mg) to male mice. Main Outcome Measures:Time to pregnancy, Luteinizing hormone (LH) levels, and testicular weight. Results:Mice treated with long-acting testosterone appear to have longer time to pregnancy when compared to wild-type (33 ± 11 vs 23 ± 2.6 days, p ? 0.05) and mice that received short-acting testosterone propionate (26 ± 5.9 days). Mice treated with long-acting testosterone had smaller testes weight when compared to control (0.08 ± 0.01 vs 0.11 ± 0.01g; p ? 0.01), while the short-acting testosterone treated mice had similar testis weight when compared to control (0.09 ± 0.02 vs 0.11 ± 0.01g; ns). The serum testosterone level was elevated in mice that received testosterone pellets (285.78 ng/dL) and testosterone propionate (122.16 ng/dL) versus control (68.4 ng/dL). In mice that received long-acting testosterone pellets, LH levels at 3 months were almost undetectable while those that received short-acting testosterone remained similar to control (0.017 ± 0.058 vs 0.348 ± 0.232 IU/L; p ? 0.01). Female reproductive potential parameters including litter size and pup weight were collected and observed to have no difference between groups. Conclusion:Through a mouse breeding study, mice that received short-acting testosterone were shown to have fertility potential similar to wild-type male mice. Long-acting exogenous testosterone appeared to impair male reproductive capacity and LH levels when compared to short-acting testosterone. Short-acting testosterone appeared to cause less LH suppression. Identifying strategies to increase testosterone while simultaneously preserving male fertility is important for treating young men with hypogonadism.

SUBMITTER: Chu KY

PROVIDER: S-EPMC7480784 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Short-acting testosterone appears to have lesser effect on male reproductive potential compared to long-acting testosterone in mice.

Chu Kevin Y KY Kulandavelu Shathiyah S Masterson Thomas A TA Ibrahim Emad E Arora Himanshu H Ramasamy Ranjith R

F&S science 20200414 1

<h4>Objective</h4>To compare the effect of exogenous short-acting and long-acting testosterone on male reproductive potential in mice.<h4>Design</h4><i>In vivo</i> mouse model.<h4>Setting</h4>University-based basic science research laboratory.<h4>Animals</h4>A total of 30 wild-type C57BL/6 male and female mice were used for this experimentation. The male mice were used for control group and testosterone supplementation, while both male and female mice were used for the breeding portion of the st ...[more]

PMID: 32914138

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Project description:The reproductive system is extremely susceptible to environmental insults, for example exogenous steroids during gestational development and differentiation. Experimental induction of androgen excess during prenatal life in female animal models reprograms their reproductive physiology, however the fetal programming of the male reproductive system by androgen excess has not been well studied. We aimed to determine the effect of prenatal exposure of two different doses of testosterone on different gestational days, on the male reproductive system using a rat model. Sixteen pregnant rats were randomly divided into two experimental groups and two control groups. Experimental group І were subcutaneously injected with 3 mg free testosterone on gestational days 16-19 and its controls received solvent for that time; experimental group П were subcutaneously injected with 20 mg free testosterone on day 20 of gestational period and its controls received solvent at the same time. The reproductive system morphology and function of 32 male offspring of these study groups were compared at days 6-30-60 of age and after puberty. The anogenital distance of the male offspring of both experimental groups had no significant differences on the different days of measurement, compared with controls. In the offspring of experimental group І, the testes weight, number of Sertoli, Spermatocyte and Spermatid cells, sperm count and motility and the serum concentration of testosterone after puberty were significantly decreased; except for reduction of sperm motility (p< 0.01), the other effects were not observed in the offspring of experimental group ІІ. In summary, our data show that prenatal exposure of male rat fetuses to excess testosterone disrupted reproductive function, an effect highly dependent on the time, duration and level of exposure. It seems that the reproductive system in individuals exposed to high levels of androgens during fetal life should be evaluated at puberty and likely to be treated.

Project description:ImportanceCardiovascular events and mortality are the principal causes of excess mortality and health care costs for people with type 2 diabetes. No large studies have specifically compared long-acting insulin alone with long-acting plus short-acting insulin with regard to cardiovascular outcomes.ObjectiveTo compare cardiovascular events and mortality in adults with type 2 diabetes receiving long-acting insulin who do or do not add short-acting insulin.Design, setting, and participantsThis retrospective cohort study emulated a randomized experiment in which adults with type 2 diabetes who experienced a qualifying glycated hemoglobin A1c (HbA1c) level of 6.8% to 8.5% with long-acting insulin were randomized to continuing treatment with long-acting insulin (LA group) or adding short-acting insulin within 1 year of the qualifying HbA1c level (LA plus SA group). Retrospective data in 4 integrated health care delivery systems from the Health Care Systems Research Network from January 1, 2005, to December 31, 2013, were used. Analysis used inverse probability weighting estimation with Super Learner for propensity score estimation. Analyses took place from April 1, 2018, to June 30, 2019.ExposuresLong-acting insulin alone or with added short-acting insulin within 1 year from the qualifying HbA1c level.Main outcomes and measuresMortality, cardiovascular mortality, acute myocardial infarction, stroke, and hospitalization for heart failure.ResultsAmong 57 278 individuals (39 279 with data on cardiovascular mortality) with a mean (SD) age of 60.6 (11.5) years, 53.6% men, 43.5% non-Hispanic White individuals, and 4 years of follow-up (median follow-up of 11 [interquartile range, 5-20] calendar quarters), the LA plus SA group was associated with increased all-cause mortality compared with the LA group (hazard ratio, 1.27; 95% CI, 1.05-1.49) and a decreased risk of acute myocardial infarction (hazard ratio, 0.89; 95% CI, 0.81-0.97). Treatment with long-acting plus short-acting insulin was not associated with increased risks of congestive heart failure, stroke, or cardiovascular mortality.Conclusions and relevanceFindings of this retrospective cohort study suggested an increased risk of all-cause mortality and a decreased risk of acute myocardial infarction for the LA plus SA group compared with the LA group. Given the lack of an increase in major cardiovascular events or cardiovascular mortality, the increased all-cause mortality with long-acting plus short-acting insulin may be explained by noncardiovascular events or unmeasured confounding.

Project description:BackgroundLong-acting reversible contraceptives (LARCs) have superior contraceptive efficacy compared to short-acting reversible contraceptives (SARCs) and choosing LARCs over SARC methods reduces the need for abortion care. However, little is known how initiating these methods associates with the subsequent overall need of reproductive health services including family planning services, and visits for gynecological reasons in primary and specialized care.MethodsWe followed altogether 5839 non-sterilized women aged 15-44 years initiating free-of-charge LARC methods (n = 1689), initiating or switching SARC methods (n = 1524), or continuing with the same SARC method (n = 2626) at primary care family planning clinics in the City of Vantaa, Finland, 2013-2014 for 2 years using Finnish national health registers. We assessed the use of reproductive health services, namely attending public primary or specialized health care for gynecological reasons or attending the family planning clinics by applying unadjusted and adjusted negative binomial regression models on visit counts.ResultsA total of 11,290 visits accumulated during the two-year follow-up: 7260 (64.3%) at family planning clinics, 3385 (30.0%) for gynecological reasons in primary, and 645 (5.7%) in specialized health care. Altogether 3804 (52.4%) visits at the family planning clinics were for routine checkup, and 3456 (47.6%) for other reasons. Women initiating LARC methods used reproductive health services for reasons other than routine checkups similarly as women initiating or switching SARC methods (adjusted incidence rate ratio 0.93, 95% CI 0.82-1.05), while women continuing with SARC methods used the services less frequently (0.65, 0.59-0.72). Women initiating free-of-charge LARC and those continuing with the same SARC method used services less for abortion care than women initiating or switching SARC (adjusted incidence rate ratios 0.05, 95% CI 0.03-0.08 and 0.16, 95% CI 0.11-0.24, respectively).ConclusionsWhile women initiating LARC methods have lower need for abortion care compared to women initiating SARC methods, women initiating both LARC and SARC methods have similar overall need for reproductive health services. In contrast, women continuing with their SARC method need reproductive health services less than women initiating LARC or a new SARC method. These service needs should be acknowledged when planning and organizing family planning services, and when promoting long-acting reversible contraception.

Project description:BackgroundIn species with biparental care both members of the breeding pair cooperate to raise the offspring either by assisting each other in every reproductive task or by specializing in different ones. The latter case is known as reproductive role specialization. Raptors are considered one of the most role-specialized groups, but little is known about parental behavior away from the nest. Until the advent of biologgers, avian role specialization was traditionally studied with direct observations at the nest because of the difficulties of following and recording the behavior of free-ranging individuals. In this paper we analyze how the role specialization of the lesser kestrel (Falco naumanni) influences foraging movement patterns throughout the breeding season. We tracked 30 lesser kestrel breeders from two breeding colonies using high-frequency GPS-dataloggers during four consecutive breeding seasons.ResultsWe found no differences between sexes in lesser kestrel foraging movements early in the breeding season before the formation of the breeding pair. However, we observed sexually distinct foraging movement strategies later in the breeding season once breeding pairs were formed. Lesser kestrel males performed a large number of short foraging trips while females made a few long ones. This maximized the provisioning rate by males to feed their mates and offspring. Meanwhile, lesser kestrel females spent more time at the colony than males in order to defend the nest, incubate the eggs and brood the nestlings. Females also helped their mates to provision the nestling once these had grown and required more food and less protection. Furthermore, lesser kestrels showed a sexual spatial segregation in foraging areas, with males foraging closer to the colony than females.ConclusionsThe lesser kestrel responds to changes in energy demand throughout the breeding season with its foraging movement strategy, but in a different way depending on parental sex. The sexual spatial segregation observed is likely to be the result of an adaptive foraging strategy based on role specialization to reduce prey depletion close to the colony and intersexual competition in order to improve breeding success.

Project description:ObjectiveTo identify specific germline mutations related to sperm reproductive competence, in couples with unexplained infertility.DesignIn this retrospective study, couples were divided according to whether they had successful intracytoplasmic sperm injection outcomes (fertile) or not (infertile). Ancillary sperm function tests were performed on ejaculates, and whole exome sequencing was performed on spermatozoal DNA. Sperm aneuploidy and gene mutation profiles were compared between the 2 cohorts as well as according to the specific reasons for reproductive failure.SettingCenter for reproductive medicine at a major academic medical center.Patient(s)Thirty-one couples with negative infertility workups and normal semen parameters.Intervention(s)Couples with mutations on fertilization- or embryo development-related genes were subsequently treated by assisted gamete treatment or microfluidics, respectively.Main outcome measure(s)Intracytoplasmic sperm injection cycle outcomes including fertilization, clinical pregnancy, and delivery rates.Result(s)Sperm aneuploidy was lower in the fertile group (4.0% vs. 8.4%). Spermatozoa from both cohorts displayed mutations associated with sperm-egg fusion (ADAM3A) and acrosomal development (SPACA1), regardless of reproductive outcome. The infertile cohort was then categorized according to the reasons for reproductive failure: absent fertilization, poor early embryo development, implantation failure, or pregnancy loss. Spermatozoa from the fertilization failure subgroup (n = 4) had negligible PLCζ presence (10% ± 9%) and gene mutations (PLCZ1, PIWIL1, ADAM15) indicating a sperm-related oocyte-activating deficiency. These couples were successfully treated by assisted gamete treatment in their subsequent cycles. Spermatozoa from the poor early embryo development subgroup (n = 5) had abnormal centrosomes (45.9% ± 5%), and displayed mutations impacting centrosome integrity (HAUS1) and spindle/microtubular stabilization (KIF4A, XRN1). Microfluidic sperm processing subsequently yielded a term pregnancy. Spermatozoa from the implantation failure subgroup (n = 7) also had abnormal centrosomes (53.1% ± 13%) and carried mutations affecting embryonic implantation (IL9R) and microtubule and centrosomal integrity (MAP1S, SUPT5H, PLK4), whereas those from the pregnancy loss subgroup (n = 5) displayed mutations on genes involved in trophoblast development (NLRP7), cell cycle regulation (MARK4, TRIP13, DAB2IP, KIF1C), and recurrent miscarriage (TP53).Conclusion(s)By assessing the sperm genome, we identified specific germline mutations related to various reproductive processes. This information may clarify elusive factors underlying reproductive competence and enhance treatment for couples with unexplained infertility.

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Short-acting testosterone appears to have lesser effect on male reproductive potential compared to long-acting testosterone in mice.

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Short-acting testosterone appears to have lesser effect on male reproductive potential compared to long-acting testosterone in mice.

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