The U54 Cooperative Contraceptive Development Research Center Grant described in this proposal includes five projects. We identified new leads to be developed into safe and effective contraceptives both for men and women and with additional health benefits to the users: (I) A new contraceptive vaginal ring will be developed using Nestorone (NES) and natural Estradiol (E2) for a safer contraception. SA1: NES/E2 rings will be designed for a first efficacy study. Potential benefits on the brain will be tested by: SA2 determining impact of hormone exposure on neurogenesis in normal brain and SA3 will evaluate the effects of NES and E2, on myelin repair both on in vitro and in vivo animal models. (II) A new progesterone receptor modulator Ulipristal (UPA/CDB-2914) will be investigated: SA1: Endometrial safety and contraceptive efficacy of a 3-month UFA vaginal ring (UPA CVR) in combination with progestin will be assessed in a 6- month clinical study. SA2: A contraceptive intrauterine system (IDS) releasing low doses of UPA to decrease endometrium and bleeding will be developed SA3: Molecular mechanisms underlying potential benefits of UPA CVR will be tested on target tissues. (Ill) The evaluation of new endothelin receptor antagonists on ovulation with the goal of developing new specific and highly effective emergency contraceptives will be conducted in collaboration with the University of Illinois (IV) MENT(r) Ac implants for male contraception with added health benefits will be tested. We will (SA1) Manufacture new one-year MENT Ac subdermal implants to (SA2) conduct an efficacy &safety study on the effect of implants alone and with Depomedroxyprogesterone acetate (DMPA) in normal men. We will: SA3: evaluate the mechanism of action of MENT when combined with progestins;SA4: evaluate the protective effect of MENT on Leydig Cells;SA5: confirm protective effects of MENT on bone when combined with DMPA. (V): Develop adjudin as a nonhormonal male contraceptive;SA1: characterize the formulation (adjudin-IMB) for clinical use in men. SA2: Unravel molecular mechanism(s) by which adjudin-IMB disrupts adhesion protein complexes at the apical ectoplasmic specialization. SA3: Complete toxicity program to prepare for clinical use in men.

Public Health Relevance

The scientific opportunities identified in the 2011 NICHD Vision Workshop on Reproduction included the need for innovative, safer methods of contraception and with added health benefits to the users. Also longlasting methods allowing improved compliance are needed. Our projects include contraceptives for men and women and have the potential to answer the above objectives and hence impact positively on global health.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HD029990-23
Application #
8720027
Study Section
Special Emphasis Panel (ZHD1)
Program Officer
Lee, Min S
Project Start
1997-03-14
Project End
2017-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
23
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Population Council
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10017
Mao, Baiping; Mruk, Dolores; Lian, Qingquan et al. (2018) Mechanistic Insights into PFOS-Mediated Sertoli Cell Injury. Trends Mol Med 24:781-793
Kannan, Athilakshmi; Bhurke, Arpita; Sitruk-Ware, Regine et al. (2018) Characterization of Molecular Changes in Endometrium Associated With Chronic Use of Progesterone Receptor Modulators: Ulipristal Acetate Versus Mifepristone. Reprod Sci 25:320-328
Xiao, Xiang; Ni, Ya; Yu, Chenhuan et al. (2018) Src family kinases (SFKs) and cell polarity in the testis. Semin Cell Dev Biol 81:46-53
Chen, Haiqi; Mruk, Dolores D; Lui, Wing-Yee et al. (2018) Cell polarity and planar cell polarity (PCP) in spermatogenesis. Semin Cell Dev Biol 81:71-77
Chen, Haiqi; Xiao, Xiang; Lui, Wing-Yee et al. (2018) Vangl2 regulates spermatid planar cell polarity through microtubule (MT)-based cytoskeleton in the rat testis. Cell Death Dis 9:340
Wen, Qing; Mruk, Dolores; Tang, Elizabeth I et al. (2018) Cell polarity and cytoskeletons-Lesson from the testis. Semin Cell Dev Biol 81:21-32
Li, Linxi; Mao, Baiping; Wu, Siwen et al. (2018) Regulation of spermatid polarity by the actin- and microtubule (MT)-based cytoskeletons. Semin Cell Dev Biol 81:88-96
Wen, Qing; Tang, Elizabeth I; Li, Nan et al. (2018) Regulation of Blood-Testis Barrier (BTB) Dynamics, Role of Actin-, and Microtubule-Based Cytoskeletons. Methods Mol Biol 1748:229-243
Chen, Shuhua; Kumar, Narender; Mao, Zisu et al. (2018) Therapeutic progestin segesterone acetate promotes neurogenesis: implications for sustaining regeneration in female brain. Menopause 25:1138-1151
Chen, Haiqi; Lui, Wing-Yee; Mruk, Dolores D et al. (2018) Monitoring the Integrity of the Blood-Testis Barrier (BTB): An In Vivo Assay. Methods Mol Biol 1748:245-252

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